Human Genome Project - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

HUMAN GENOME PROJECT A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES ...

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HUMAN GENOME PROJECT A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Human Genome Project: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83931-X 1. Human Genome Project-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on human genome project. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON HUMAN GENOME PROJECT ...................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Human Genome Project................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 39 The National Library of Medicine: PubMed ................................................................................ 40 CHAPTER 2. NUTRITION AND HUMAN GENOME PROJECT ............................................................ 81 Overview...................................................................................................................................... 81 Finding Nutrition Studies on Human Genome Project............................................................... 81 Federal Resources on Nutrition ................................................................................................... 82 Additional Web Resources ........................................................................................................... 83 CHAPTER 3. ALTERNATIVE MEDICINE AND HUMAN GENOME PROJECT ...................................... 85 Overview...................................................................................................................................... 85 National Center for Complementary and Alternative Medicine.................................................. 85 Additional Web Resources ........................................................................................................... 90 General References ....................................................................................................................... 91 CHAPTER 4. DISSERTATIONS ON HUMAN GENOME PROJECT ........................................................ 93 Overview...................................................................................................................................... 93 Dissertations on Human Genome Project.................................................................................... 93 Keeping Current .......................................................................................................................... 94 CHAPTER 5. PATENTS ON HUMAN GENOME PROJECT .................................................................. 95 Overview...................................................................................................................................... 95 Patent Applications on Human Genome Project ......................................................................... 95 Keeping Current .......................................................................................................................... 98 CHAPTER 6. BOOKS ON HUMAN GENOME PROJECT ...................................................................... 99 Overview...................................................................................................................................... 99 Book Summaries: Federal Agencies.............................................................................................. 99 Book Summaries: Online Booksellers......................................................................................... 100 The National Library of Medicine Book Index ........................................................................... 103 Chapters on Human Genome Project......................................................................................... 104 CHAPTER 7. MULTIMEDIA ON HUMAN GENOME PROJECT ......................................................... 105 Overview.................................................................................................................................... 105 Bibliography: Multimedia on Human Genome Project ............................................................. 105 CHAPTER 8. PERIODICALS AND NEWS ON HUMAN GENOME PROJECT ...................................... 107 Overview.................................................................................................................................... 107 News Services and Press Releases.............................................................................................. 107 Newsletters on Human Genome Project .................................................................................... 109 Academic Periodicals covering Human Genome Project ........................................................... 110 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 113 Overview.................................................................................................................................... 113 NIH Guidelines.......................................................................................................................... 113 NIH Databases........................................................................................................................... 115 Other Commercial Databases..................................................................................................... 117 APPENDIX B. PATIENT RESOURCES ............................................................................................... 119 Overview.................................................................................................................................... 119 Patient Guideline Sources.......................................................................................................... 119 Finding Associations.................................................................................................................. 125 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 129 Overview.................................................................................................................................... 129 Preparation................................................................................................................................. 129

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Finding a Local Medical Library................................................................................................ 129 Medical Libraries in the U.S. and Canada ................................................................................. 129 ONLINE GLOSSARIES................................................................................................................ 135 Online Dictionary Directories ................................................................................................... 135 HUMAN GENOME PROJECT DICTIONARY........................................................................ 137 INDEX .............................................................................................................................................. 171

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with human genome project is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about human genome project, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to human genome project, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on human genome project. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to human genome project, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on human genome project. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON HUMAN GENOME PROJECT Overview In this chapter, we will show you how to locate peer-reviewed references and studies on human genome project.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and human genome project, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “human genome project” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Dental Implications of the Human Genome Project Source: CDA Journal. Journal of the California Dental Association. 29(1): 35-47. January 2001. Contact: Available from California Dental Association (CDA). 1201 K Street, Sacramento, CA 95814. (916) 443-0505. Summary: This article considers the dental implications of the Human Genome Project. Researchers have identified about 300 known dental genes thus far and about 1,000 diseases and disorders with major orodental complications. However, as yet there is no treatment for almost all of the problematic genes. To match the sometimes ominous results of sophisticated genetic screening tests, dentists have only standard therapies: a

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Human Genome Project

scaler, a chip soaked with medicine, and a graft. This article includes interviews with top government, academic, and industry experts on dental genetics to profile what is known about the science, legal, ethical, insurance, and clinical aspects of genetics in dentistry. Dental school and continuing education, privacy, and future therapeutic issues are addressed with an emphasis on how patients' genetics are just now beginning to affect the dental practice. One sidebar reviews some of the facts about the Human Genome Project, its funding, progress, and potential benefits. Another sidebar lists genetic web sites where readers can get additional information. 6 figures. •

Impact of the Human Genome Project on Oral Health Care Source: Access. 15(5): 36-46. May-June 2001. Contact: Available from American Dental Hygienists' Association. 444 North Michigan Avenue, Chicago, IL 60611. Summary: Until the present time of the genome mapping project, the diagnosis and treatment of human disease has been speculative in nature. That is, health care providers have been managing diseases only after signs and symptoms appear. However, with genetic testing capabilities, the development of diseases, including oral disease, can be predicted and identified long before the symptoms appear. This article describes the potential impact of the human genome project on oral health care. The author describes the genome project and hypothesizes about the applications of the information gleaned from a better understanding of human genetics. Topics include the origins of disease, simple versus complex disease, array technology, screening for periodontal disease, the debate surrounding the value of screening tests, microbial genomics (searching for more effective ways to kill the microorganisms that live in the mouth), oral infection and systemic disease, ethical considerations, insurance, employment, and genetics in the dental hygiene curriculum. One sidebar offers a detailed glossary of genetics terms; another sidebar lists useful genome related web sites. 4 figures.

Federally Funded Research on Human Genome Project The U.S. Government supports a variety of research studies relating to human genome project. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to human genome project. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore human genome project. The following is typical of

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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the type of information found when searching the CRISP database for human genome project: •

Project Title: A EMBRYOGENESIS

SYSTEMATIC

RNAI-BASED

MAP

OF

C.

ELEGANS

Principal Investigator & Institution: Piano, Fabio; Biology; New York University 15 Washington Place New York, Ny 10003 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): One of the next major goals of the Human Genome Project is to identify the function of all the genes it encodes. Arguably the greatest challenge lies in determining the in vivo functions for large sets of genes and how they orchestrate the complex processes of the cell, and animal models can play a significant role in guiding in vivo functional annotation of the human genome. C. elegans is well established as an important model system in which to study the molecular genetics of cell biology and animal development and has also become a leading model for functional genomic research; the early embryo in particular is an excellent system in which to study basic cell biological and developmental processes. RNA interference (RNAi) is a rapid reverse genetics approach to identify the in vivo functions of genes, and several large-scale RNAi scans in C. elegans have so far led to the identification of over 1,500 genes required for embryogenesis. By systematically annotating the functions of such genes in detail using time-lapse microscopy of early embryogenesis, specific cellular roles for over 200 genes have been discovered; however, it is estimated that at least an additional 1000 genes essential for embryonic development remain to be identified. The next step now required is to provide a systematic, detailed functional characterization of all the genes that play a role in this system - a "phenotypic map" of in vivo functions to lay the foundation for integrative systems biology approaches. The goal of this project is to use RNAi to produce a high-resolution phenotypic map of early embryogenesis in C. elegans: a detailed functional description of all the genes required for basic cellular, subcellular, and developmental processes in the early embryo. To accomplish this goal, single-gene RNAi of all approximately 12,000 validated ORFs cloned by the ORFeome project will be performed to assay embryonic lethality and carry out systematic detailed phenotypic analysis of early embryogenesis using DIC optics. An online database, RNAiDB, will be used for all aspects of this study: data collection, scoring, analysis, and distribution. Phenotype-based bioinformatic analysis will be performed, including gene clustering based on phenotypic data and integration with other types of functional genomics data, to identify groups of genes with similar functions and to extend functional annotations, for unknown proteins in particular. The results of these analyses will be used to select groups of genes for further study using a set of subcellular markers to assay specific processes (e.g. chromosome segregation, cytoskeletal organization, cell polarity and cell fate). These secondary studies will be used both to test hypotheses generated from earlier phenotypic and bioinformatic analyses, as well as to generate more in-depth data on the functions of particular gene sets. Since many of these basic functions are carried out by highly conserved proteins, the data gathered in this project will be immediately useful to guide the functional annotation of the human and other genomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIPOLAR DISORDER CANDIDATE GENES ON CHROMOSOME 18Q22 23 Principal Investigator & Institution: Prathikanti, Sridhar; Psychiatry; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 10-JUL-2001 Summary: (provided by applicant): Chromosome 18q 22-23 has been linked to bipolar affective disorder (BPAD) in several studies. We have identified in our sample pedigrees that define a strongly linked 6 MB region on 18q22 with a lod score of 4.85. The Specific Aims of this research training proposal are to 1) Identify candidate genes in and around the BPAD linkage region on 18q22-23 by screening sequence data from the Human Genome Project; 2) To identify single nucleotide polymorphism markers (SNP?s) in and near these candidate genes in and near these candidate genes by mining the public databases and by re-sequencing PCR products in our laboratory; 3) To genotype selected SNP?s in 2-4 positional candidate genes using single base extension and other high throughput methods; 4) To test each gene for association with BPAD in a sample of 400 triads, using family based statistical methods. This project will offer me a complete experience in positional candidate gene research, forming the basis for my future career. Identification of the genes that predispose to BPAD would offer novel and powerful insights into the etiology and ultimately the treatment of BPAD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANCER GENETICS Principal Investigator & Institution: Goodfellow, Paul J.; Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 02-AUG-2001; Project End 30-JUN-2004 Summary: The Cancer Genetics Program includes 34 Washington University School of Medicine faculty. The members of the Program have expertise in genomics, statistical approaches to the identification of genetic factors that contribute to the disease, molecular and clinical genetics and cancer biology. Research efforts focused on gaining a greater understanding of the genetic basis of tumor initiating and progression which will ultimately make possible new approaches to the prevention and treatment of human malignancies. It is the Program member's goal new approaches to the prevention and treatment of human malignancies. It is the Program member's goal to collaborate to develop new methods for cancer genetics research that will take advantage of the unparalleled advances in genetics that have come from the Human Genome Project. Members that will take advantage of the unparalleled advances in genetics that have come from the Human Genome Project. Members will work together to develop and apply new methods for mapping and identifying genetic factors that contribute to cancer risk, and will also develop methods to define specific gene/environment interactions that are important in tumorigenesis Members of the Cancer Genetics Program will continue to develop clinically relevant methods to identify patients and families who are at increased risk for an inherited malignancy, to identify and characterized new tumor suppressors and genes that modify risk for the development of cancer. With the advent of high throughput multiplexed gene analysis, members will begin to profile molecular changes in tumors and to use that information to direct patient treatment. Many of the Cancer Genetics Program members are also members of organ or disease site focus groups within the Clinical and Translational Research Program. This interaction with clinical investigators ensures that laboratory investigators are aware of clinically important research issues and that clinicians are

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made aware of advances in cancer genetics that may prove to relevant to patient care. The Cancer Genetics Program members will play a key role in cancer genetics education at Washington University School of Medicine and the Siteman Cancer Center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL-FREE PROTEIN LABELING FOR DRUG DISCOVERY Principal Investigator & Institution: Gite, Sadanand; Senior Scientist; Ambergen, Inc. 1106 Commonwealth Ave Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-SEP-2002 Summary: (Applicant's abstract): The completion of the human genome project has opened a new chapter in drug discovery. In contrast to conventional methods, where a drug library is screened against a single protein, the entire proteome is now available for screening. However, such drug-proteomic screens are difficult to accomplish using conventional technology because of the need to rapidly convert genome to proteome, engineer specially labeled proteins and screen thousands of samples per hour. This project aims to remove these limitations by screening drug-protein interactions using cell-free expressed labeled proteins and 2-D microarrays. AmberGen will evaluate a series of tags, which are incorporated into proteins during their cell-free expression. Fluorescent tags provide a means to monitor protein expression and detect their interactions with potential drug compounds. Affinity tags provide a means to rapidly isolate cell-free expressed proteins from the cell-free lysate. Drug screens performed on 2-D microarrays of cell-free expressed proteins, reflecting all or part of the human proteome, will be developed which have high sensitivity detection, high throughput and low sample volume requirements. Affymetrix will provide assistance by providing access to their 2-D microarray technology. In Phase II, a proteome on a chip screening system will be developed for sale to pharmaceutical companies. PROPOSED COMMERCIAL APPLICATION: The development of a cell-free based protein expression approach to drug discovery will result in an array of commercial products including reagents and hardware for drug- protoemic screening and an integrated proteome on a chip screening system. AmberGen is currently involved in discussions with companies to form strategic alliances to market these systems. A market which exceeds $2 billion/year is projected for these products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CENTER FOR GENOME RESEARCH Principal Investigator & Institution: Lander, Eric S.; Director; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2001; Project Start 08-MAR-1999; Project End 31-OCT-2003 Summary: Under NHGRI's sequencing pilot project, the Whitehead/MIT Center for Genome Research has developed a scalable and efficient process for genomic sequencing. The specific aim of this proposal is to convert our pilot project to a production center by: (i) increasing lane capacity to 20 M lanes per year, by expanding our automated systems for sample prep and purchasing a fleet of capillary sequencers; and (ii) achieving a production rate of finished sequence of at least 750 Mb per year at a cost of 10 cents/base including overhead. We are also committed to working closely with NHGRI and other centers to adapt to rapidly changing circumstances, to ensure the overall rapid success of the Human Genome Project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROPATHIES

CHARACTERIZATION-NOVEL

SUBTYPES-INHERITED

Principal Investigator & Institution: Lawson, Victoria H.; Neurology; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2002; Project Start 21-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The goal of this project is to clinically characterize and define gene mutations responsible for novel and unusual forms of inherited neuropathies (Charcot-Marie-Tooth) in large Utah families. Charcot-Marie-Tooth (CMT) is one of the most common degenerative neurological disorders with a prevalence of 1 in 2500. It is a clinically heterogeneous group of disorders with distal limb muscle weakness, wasting, and sensory loss usually presenting in childhood or early adulthood and typical skeletal abnormalities. The broad classification of CMT into types 1 and 2 based on electrophysiology and pathology is giving way to genetic classification, reflecting significant genetic heterogeneity. At least 10 CMT gene loci have been defined. The applicant proposes to identify and extensively phenotype novel and unusual forms of CMT by studying large kindreds. Linkage analysis will be performed, then a genome wide screen using polymorphic markers across the genome. Candidate genes in the region of linked loci will be identified from the growing Human Genome Project database and mutation analysis will be performed. One large Utah kindred with an axonal form of CMT has already been studied in detail and no linkage to described loci has been found. Therefore, this represents a completely novel form of axonal CMT. A genome-wide screen for linkage is underway. To date 221 screening markers across the genome have been genotyped, and of these, 1 candidate locus has been identified with a LOD score of nearly 2. Four additional large kindreds have been ascertained: Historical data has been collected on many of these family members and clinical/ electrophysiologic examination is underway. The largest kindred has a maximum simulated LOD score of 9.74. Preliminary data suggest these families may be phenotypically distinct from the family already described and, in at least one kindred, from previously described phenotypes. Therefore, these families may represent additional novel loci. Through an NIH funded K30 award, the University of Utah General Clinical Research Center provides a unique didactic program of training in clinical research focused on the inherited basis of human disease. This program incorporates access to resources such as multiuser core facilities, large research centers at the University, and a designated unit in the University Hospital, with specific, mentored, intensive research experiences for maturing clinical investigators. Thus, the University of Utah provides an ideal environment for maximizing the potential of this project and this project applicant. Molecular characterization of novel and unusual forms of CMT will define basic biologic processes of peripheral nerve function, and may lead to new diagnostic and therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RETARDATION

CHROMOSOME

REARRANGEMENTS

AND

MENTAL

Principal Investigator & Institution: Lupski, James; Professor; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 11-JUN-2001; Project End 31-MAY-2006 Summary: Chromosomal abnormalities are responsible for a significant fraction of children with mental retardation. Advances in molecular cytogenetic techniques as well as the tremendous progress of the Human Genome Project, have now made it possible

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9

to determine the molecular basis of chromosomal abnormalities. From patients with specific chromosome rearrangements including (i) balanced translocations, (ii) interstitial deletion/duplication and (iii) terminal deletion. The q11 region of chromosome 22 is susceptible to a multitude of rearrangements including translocations, leading to congenital anomalies and malignant disorders. Deletions and duplications of 17p11.2 are associated with Smith-Magenis syndrome and a mental retardation syndrome, respectively. Both the 22qll and 17p11.2 rearrangements may be mediated by low-copy repeat sequences that occur in the vicinity of recurrent chromosome breakpoints. Novel terminal deletions of the 1p36 region delineate a new mental retardation disorder with a different mechanism of rearrangement since the deletion end-points very significantly among patients. The three chromosomal regions will serve as models for our Program. We will examine the intervals that harbor the chromosome breakpoints by fluorescence in situ hybridization in situ hybridization (FISH) and pulsefield gel electrophoresis (PFGE) mapping approaches and breakpoint junctions will be cloned and sequenced to determine the mechanism of rearrangement. This projects will be integrated with a fourth project to determine the evolutionary basis of these regions that are prone to breakage in humans. Our functional genomics approach will capitalize on vast resources of DNA samples, cell lines, and Genome Project, as well as cell lines and reagents from non-human primates, that are available to the individual Project P.I.'s. Results from these studies will greatly impact our understanding of chromosome rearrangement causing mental retardation, will likely lead to development of novel diagnostic tools and may change the way medical genetics is practiced with regard to families having an individual with a chromosome rearrangement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COATING FOR IMPROVED SENSITIVITY AND RANGE OF MICROARRAY Principal Investigator & Institution: Rosebrough, Scott F.; Sts Biopolymers, Inc. 336 Summit Point Dr Henrietta, Ny 14467 Timing: Fiscal Year 2002; Project Start 12-FEB-2002; Project End 30-NOV-2002 Summary: (provided by applicant): An important development in medicine has been the ability to quickly and reliably screen individuals for diseases and more recently genetic markers which may pre-dispose individuals to develop illnesses during their lifetime. The development of clinical diagnostics based on gene expression profiles is approaching maturation due to genetic information gathered by the Human Genome Project, the generation of animal models to study human disease and many other genomic and proteomic approaches being applied to decipher the molecular pathogenisis of disease over the last decade. One product of these advances is the need to increase probe densities on microarray surfaces. STS Biopolymers is developing a three-dimensional surface treatment (GRAFT-COATTM) that will allow an increase in the density of genetic markers onto microarrays. The Phase I portion of this project will determine the variables that determine the sensitivity and dynamic range of GRAFTCOATTM. microarray surfaces. Surfaces capable of binding a range of protein and genetic probes will be prepared. Finally, the performance of GRAFT-COATTM microarrays printed with protein and DNA probes will be compared to those of surfaces used currently. In Phase II we will focus on coating formulations providing the highest sensitivity and broadest dynamic range for further development and miniaturization. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Human Genome Project

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Project Title: COMPUTER HARDWARE FOR SEQUENCE ANALYSIS Principal Investigator & Institution: Hughey, Richard; University of California Santa Cruz 1156 High St Santa Cruz, Ca 95064 Timing: Fiscal Year 2001; Project Start 12-JUL-2001; Project End 30-JUN-2006 Summary: We plan to provide bioinformatics support to the Human Genome Project, and work with the Whitehead Institute for Biomedical Research/MIT Center for Genome Research on comparisons between human and other vertebrate genomes. We will continue to supply monthly assemblies of the currently available human genome sequence, which we have provided since May 2000. Along with each assembly we will provide an integrated database of links to ESTs, mRNAs, SNPs, gene predictions, markers, isochores, contigs, gaps, clones, and homologies with other vertebrates, mapped to specific positions on the assembled genome and viewable side-by-side on the web through an interactive browser. This web browser will facilitate the use of the primary working draft and finished human genome data, stored by NCBI and EBI, by medical and scientific researchers worldwide. In addition to our support role, we propose to develop new methods to use comparative genomics, computational algorithms, and microarray technology to uncover the structure and function of human genes. Sequence homologies with the genes of other vertebrates, combined with EST and mRNA data, will be used to determine gene structure, alternative splicing, and regulatory motifs for human genes. Custom microarrays will be built with specific oligos designed to confirm splicing and regulation for the for the most medically important genes. Hidden Markov models will be built to model the domain structure of the protein products, and suggest functional classification by homology. Expression data will be combined with predicted structural features and data from external sources to produce the most comprehensive computational and experimental classification possible. The centerpiece of the proposal is a 1000 CPU computer cluster, funded jointly by Howard Hughes Medical Institute and through this award from NHGRI, which will enable us to perform the necessary genome-wide computations. Funding from the Sloan Foundation and internal funding from the UCSC campus will also provide support for the development of M.S. and Ph.D. programs in bioinformatics. The other financial component of the proposal is for staff and student support. By focusing funds from several sources, we are able to train a new generation of scientists, explore new research methodologies, and provide a vital service for the Human Genome Project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONCERNS INTERVENTIONS

OF

EVANGELICALS

ABOUT

GENETIC

Principal Investigator & Institution: Davis, John J.; Gordon-Conwell Theological Seminary Seminary South Hamilton, Ma 01982 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2004 Summary: The objective of this proposed historical and analytical study is to identify the major ethnical concerns of Evangelical ("Born Again") Protestant Christians in the United States relative to genetic research and the Human Genome Project during the time period 1956 to the present. The method employed will be a content analysis of books and articles published by Evangelical authors, at both the scholarly and popular levels, with special concern for keywords such as "genetics", "genetic engineering" "genetic testing/screening", "gene/genetic therapy", "cloning", and "Human Genome Project." The scope of the data set to be examined will be defined by the indexing of the books and periodicals in question by the ATLA (American Theological Library

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Association) Religion Database on CD-ROM, including Religion Index One: Periodicals. The value and health-relatedness of this study will be to assist scientific researchers to more effectively interpret and communicate new findings in genetics to Evangelical Protestants and other religious communities, so as to maintain and enhance public support for research in these areas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONSTRUCTION MICROARRAY

OF

A

TARGETED

RHESUS

MACAQUE

Principal Investigator & Institution: Norgren, Robert B.; Associate Professor; Cell Biology and Anatomy; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2003; Project Start 18-JUN-2003; Project End 30-APR-2008 Summary: (provided by applicant): The rhesus macaque (Macaca mulatta) offers unique opportunities for biomedical research due to similarities to humans in both anatomy and physiology. Vaccine development for HIV and possible bioterrorist agents such as small pox and anthrax require the use of nonhuman primates (NHPs). The rhesus macaque is also the animal of choice for studies of reproductive biology and higher cortical functions. Important studies in these areas are currently impeded by the lack of a critical tool - expression microarrays. The objective of this proposal is to create rhesus macaque expression microarrays by targeted polymerase chain reaction (PCR) amplification of monkey homologs of human genes using information from the human genome project. To maximize scientific and biomedical impact, this targeted approach will be prioritized in three ordered stages. The first stage will be to produce a focused array of 1,800 genes chosen as highest priority by the NHP community. The second stage will be to identify and amplify those monkey genes for which human probes work poorly. The third stage will be to amplify the remaining rhesus macaque genes. Genes already cloned from rhesus cDNA libraries will be excluded from this project. Each stage will have four steps: (1) identify the genes; (2) design primer pairs for targeted amplification of those genes; (3) amplify, subclone, sequence, annotate, and deposit those gene clones; and (4) construct targeted rhesus expression microarrays. This project will produce a resource of major importance to the NHP community. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--GENE DISCOVERY BIOINFORMATICS Principal Investigator & Institution: Vasmatzis, George; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 31-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The Gene Discovery/Bioinformatics Core (GDBC) of this Specialized Program of Research Excellence (SPORE) provides a program to analyze public and private genomic data related to prostate and to supply leads to the other SPORE projects of interesting genes that would be utilized to accomplish their goals as well as to facilitate discovery of novel prostate genes that would be useful for diagnosis or therapy. With the human genome project close to completion, and sequence information pouring into databases from many other projects (e.g. CGAP) genomic data is becoming one of the most valuable resources for cancer projects. The GDBC aims to analyze and utilize this information in order to be a resource of interesting leads to genes for all the other SPORE projects. More specifically, the GDBC will analyze the Expressed Sequence Tags (ESTs) that derive from high quality cDNA libraries produced from normal and tumor prostate cells. This analysis, in conjunction with data from

12

Human Genome Project

micro-array gene expression profiling, will provide diagnostic markers for Project x, and candidates for immune therapy and Gene therapy (Project y, z). Analysis of the sequences derived from the human genome project and in conjunction with data from cDNA libraries and expression profiling of micro-arrays can aid the Prognostic Marker Projects. This goal will be achieved by analyzing the information in the Expressed Sequence Tag (EST) database which contains more than two million partial sequences of cDNA clones from cDNA libraries extracted from different human organs or cell types. About 70,000 ESTs are derived from normal prostate, prostate cancer, and prostate celllines. By comparing these ESTs with each other using computer algorithms, we can group ESTs in clusters that correspond to distinct genes, estimate the level of expression of genes, and define their expression patterns in different tissues or cell types. Similarly, we will obtain differential expression levels of genes in cancer vs. normal prostate tissue. Such genes can be markers for diagnosis or predictors for the aggressiveness of the disease. We will also select clusters corresponding to genes that express in prostate but not in any essential tissues and can be used as targets for immunotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DESIGN AND ANALYSIS OF HUMAN GENE MAPPING STUDIES Principal Investigator & Institution: Boehnke, Michael L.; Professor; Biostatistics; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 28-SEP-1988; Project End 31-AUG-2005 Summary: The Human Genome Project is providing outstanding resources for the identification of genes that predispose to human diseases: more and better genetic markers, a burgeoning catalog of human sequence variation, a draft sequence of the human genome, and increasingly detailed annotation of the sequence with genes and ESTs. These resources will be critical as we seek to unravel the complex etiologic basis of common human diseases. In this proposal, I address a set of statistical problems that arise in human disease gene mapping. I describe how my colleagues and I will address these problems through analytic methods and computer simulation, and how we will generalize these solutions through the production and distribution of efficient computer software. First, we will carry out statistical design and analysis work to establish the utility and permit the use of an experimental method for haplotype determination called conversion in linkage disequilibrium and linkage studies. We will assess efficiency, develop statistical algorithms to construct haplotypes from conversion-based genotype data, and develop methods and algorithms required for statistical analysis. Second, we will continue to develop and test methods for linkage mapping of genes for complex human diseases. We will: develop methods to minimize etiologic heterogeneity; build a framework for mapping complex and quantitative traits based on the generalized linear mixed model; continue to investigate issues of data quality in gene mapping studies; and address issues in localizing genes for complex human diseases when combining data from several different genome scans. Third, we will develop, test, distribute, and support computer software based on the methods that arise from the other goals of this project, and will continue to update, distribute, and support our current software, including SIMLINK, RHMAP, RELPAIR, SIBMED, and several modules of the MENDEL package. Finally, we will continue to be opportunistic in identifying and addressing important statistical modeling and analysis problems that are related to the other goals of this project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF GENE PATENTS ON GENETIC TESTING AND RESEARCH Principal Investigator & Institution: Cho, Mildred K.; Senior Research Scholar; Center for Biomedical Ethics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 21-AUG-2000; Project End 31-JUL-2003 Summary: Genes and other sequences discovered through the Human Genome Project and large-scale sequencing efforts by private biotechnology companies are being rapidly patented by non-profit academic and for-profit institutions. This recent phenomenon raises important policy questions for both health care and basic biomedical research. Many gene sequences, including expressed sequence tags and single nucleotide polymorphisms are particularly useful for developing predictive or diagnostic tests and downstream therapies. Because many patented genetic tests may fall within the standard of medical care, it is very important to examine whether current patent law and licensing procedures are behaving as intended, to enhance the public's access to new beneficial technologies. It is also important to know how research and development is affected by patenting of the tests. Although the effects of these patents on clinical genetic testing and related research may be broad and substantial, virtually nothing is known about these effects. On the one hand, intellectual property practices in biotechnology may provide important incentives for research that leads to innovations in genetic tests and treatment. On the other hand, others have argued that intellectual property laws and their implementation are not necessarily well suited for genetic technologies, and could deter innovation and commercialization. The proposed project will use case studies and a survey, combining qualitative and quantitative approaches, to describe and analyze the effects of a particular class of patents (those that claim DNA sequences for use as a genetic test). We will examine the effects on (1) provision of DNA-based genetic testing services, and (2) research and development of other genetic tests or therapies based on disease-gene associations at academic and commercial institutions. We will use the theory of anticommons developed by Heller and Eisenberg as the basis for a theoretical framework for identifying circumstances under which patents act as incentives or disincentives to genetic testing research, commercialization, and clinical services. This research will build a model for explaining the impact of patenting on clinical practice, research and development. Our analysis will form inform public policy by indicating whether intellectual property policies or their implementation should be changed to encourage research and technology transfer, and if so, how. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ETHNICITY, CITIZENSHIP, FAMILY: IDENTITY AFTER THE HGP Principal Investigator & Institution: Elliott, Bruce Carl.; Associate Professor; Center for Biomedical Ethics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-MAY-2000; Project End 31-JUL-2004 Summary: Genetic mapping and DNA specification allow for dramatically reconsidered notions of social coherence, affiliation, and social identity. At the same time, America as a society and nation-state is struggling with the meaning of inclusion and diversity. This discourse is marked by appeals to both biological and social constructions of race and ethnicity. Into this moment of social tension, the scientific results of the Human Genome Project offer a tangible claim to truth, relating origin to self and identity with a renewed sense of certainty. Such a moment calls forth deeply challenging questions. This project

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Human Genome Project

will bring together an interdisciplinary working group of scholars to explore these questions. During a three year period, it will meet to develop the language, criteria, and conceptual framework for exploring issues related to genetic variation research and social identity. Specifically the project will address ways in which the information emerging from research into human genetic variation may affect three overlapping domains: concepts of identity and authenticity; concepts of identity and community; and concepts of identity, family, and kinship. The multidisciplinary working group that will explore these complex and novel issues includes scholars from genetics, philosophy, religious studies, sociology, cultural anthropology, and history, as well as scholars whose work is intimately tied to questions of race and ethnicity, such as those working in African-American studies, Jewish Studies, and Native American Studies. At the end of the project, we will be prepared to both publish the scholarly discourse to the academic community and to disseminate the results of our reflections to a wider audience via the Internet. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATION EDUCATIONAL KIT

OF

THE

HUMAN

GENOME

PROJECT

Principal Investigator & Institution: Fealk, Elizabeth R.; Goodman Research Group, Inc. 30 Jfk St, 3Rd Fl Cambridge, Ma 02138 Timing: Fiscal Year 2002; Project Start 12-JUN-2002; Project End 31-AUG-2003 Summary: (provided by applicant): As a part of their work on the U.S. Human Genome Project, NHGRI has produced a multimedia educational kit, The Human Genome Project: Exploring our Molecular Selves. The kit (which could only be ordered online) is intended to reach a wide variety of audiences including high school biology teachers and students as well as other educators, scientists, healthcare professionals, and college students. Long-term goals of this resource are to increase access to current information about the Human Genome Project, to enhance science education, and to enhance presentations and discussions about the Human Genome Project, genetics, and genomics. The proposed research is an outcome evaluation of this multimedia education kit, to: (a) measure the effects of this resource on the community, including both users of the materials and those who will benefit from its use (e.g., students), and (b) assess its effectiveness in meeting the above-mentioned project goals. Specific evaluation objectives include: 1) identifying who ordered the kit to establish a picture of its reach, 2) exploring the extent to which recipients perceive their access to the latest information about the Human Genome Project to be improved, 3) examining use of kit and determining factors that predict extent of use among recipients (e.g., grade and subject taught, place of employment, level of supervisor support), 4) assessing its perceived effectiveness among teachers and students in enhancing high school science education, and 5) assessing its perceived effectiveness among the range of users in enhancing presentations and discussions about the Human Genome Project, genetics, and genomics. Using a sample of kit recipients, the evaluation will employ both online and mail surveys and phone interviews in the collection of quantitative and qualitative data. Post-only data will be collected from recipients during the school year to assess plans for use, actual use, and perceived outcomes of use regarding the specific areas of interest to NHGRI, as described above. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DETECTION

FANCONI

ANEMIA--HETEROGENEITY

AND

Principal Investigator & Institution: Auerbach, Arleen D.; Genetics/Hematology; Rockefeller University New York, Ny 100216399

15

CARRIER Lab/Human

Timing: Fiscal Year 2001; Project Start 01-MAY-1985; Project End 30-JUN-2002 Summary: The purpose of this study is to determine the genetic basis of Fanconi anemia (FA), an autosomal recessive disorder characterized by diverse congenital abnormalities, and a predisposition to bone marrow failure and malignancy, particularly acute myelogenous leukemia (AML The specific objectives of this project are: (1) To identify mutations in the genes for FA complementation group A (FA-A) and group C (FA-C) and other FA genes when they are isolated, and to make genotype-phenotype correlations; (2) To develop screening methods using DNA technology, for FA diagnosis and carrier detection. (3) To isolate and clone other FA genes by a combination of positional and functional complementation; (4) To study the structure and expression of these other genes. A major resource and unique feature of this proposal is our access to a large number of patients with FA exhibiting the full spectrum of its diverse features, through the International Fanconi Anemia Registry (IFAR) maintained by us at the Rockefeller University. This provides us with phenotypic information on FA patients as well as a source of cells for molecular studies; we currently have DNA samples from a total of 422 patients affected with FA. Understanding the genetic defect in FA should lead to a better understanding of birth defects and cancer predisposition in general, and the interaction of genetic and epigenetic factors in their pathogenesis. Mutation screening will initially be performed by sizing PCR amplified fragments from cDNA, by genomic DNA blot hybridization and by restriction endonuclease fingerprinting (REF). As mutations are characterized at the genomic level and sequenced, ARMS assays will be developed to permit rapid DNA based screening methods for (1) assignment of FA patients to complementation group, (2) prenatal diagnosis in FA families, and (3) identification of carriers in FA families and in populations at risk. It is an objective of this project to extend our ability to define the FA genotype of all patients and to make genotype-phenotype correlations. This would enable physicians to better predict clinical outcome and aid decision-making regarding major therapeutic modalities for this clinically heterogeneous disorder. A positional cloning approach will be used to clone the FAB and FAE genes, made feasible by the detailed physical mapping information that is rapidly becoming available through the Human Genome Project. Linkage analysis will be used to map these loci; cDNAs will be isolated by direct selection from cosmid contigs from the appropriate region. This will be combined with functional complementation in an effort to accelerate the identification of these genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL GENOMICS AND TECHNOLOGY Principal Investigator & Institution: Davis, Ronald W.; Professor; Biochemistry; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 28-SEP-1990; Project End 31-JUL-2005 Summary: (provided by applicant): The completion of the human genome project pushes us towards the next daunting task; namely that of translating sequence information into functional information. As in the case of the sequencing effort, this will necessitate innovative biological approaches combined with the development of new technologies. Approaches to functional genomics include whole genome deletion and mutation studies in model organisms as well as high-throughput mapping of complex

16

Human Genome Project

traits in both human and model organisms through the use of polymorphism detection and resequencing. We propose to develop new functional genomics approaches to the study of Saccharomyces cerevisiae and human. Studies in S. cerevisiae employ a complete collection of bar coded yeast deletion strains for quantitative phenotypic analysis of fundamental cellular pathways as well for the identification of inhibitory compounds that act against every novel essential gene product. Other approaches to the elucidation of gene function and cellular pathways include mapping of complex traits using dense marker maps, the synthesis of every possible single base/amino acid mutation in any gene of choice, and the use of mass spectrometry to identify all small metabolites. We propose to extend these studies to human through genome-wide scanning for mutations and splicing defects. These ambitious goals will only be attainable through technological innovation in the areas of higher throughput sequence determination techniques (Pyrosequencing, HPLC, barcoded genotyping), low cost oligonucleotide and gene synthesis, and microarray automation and cost reduction. In addition, bioinfonnatics tools and databases that allow the integration of a large amounts of diverse data structures will need to be developed in order to maximize the deconvolution of vast amounts of biological data into biological function. All of these components will be tested in an implementation project to validate the technology and to enable its export from our laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL GENOMICS OF PRION DISEASE Principal Investigator & Institution: Carlson, George A.; Director and Senior Scientist; Mc Laughlin Research Ins for Biomed Scis for Biomedical Sciences, Inc. Great Falls, Mt 59405 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant) Biochemical, immunological, genetic and transgenetic experiments all indicate that the prion protein (PrP) is central to prion replication and disease susceptibility. Infectious prions are composed of a diseasespecific PrP isoform designated PrPsc, and allelic forms of the PrP gene (Prnp) determine scrapie incubation time in mice. Mutant alleles of the human PrP gene (PRNP) are linked to familial prion diseases, and mice homozygous for a null allele of Prnp are resistant to prion disease and fail to support prion replication. However, additional factors impinge on prion replication and prion disease. Studies exploiting chimeric PrP transgenes and Prnp null mice suggest that efficient prion replication involves at least one auxiliary molecule, designated protein X. Both scrapie incubation time and the areas of the brain that are affected can differ dramatically among inbred strains of mice that express identical PrP molecules following infection with a single strain of scrapie. Treating prion incubation time as a quantitative trait led to the identification of at least two modifier genes. To identify the genes underlying these quantitative trait loci (QTLs), the QTL intervals will be isolated in congenic strains and the interval narrowed though high resolution mapping. The congenic strains also will be used to characterize the effects of each QTL on incubation time, pathology, distribution of PrPsc in the brain, PrP biochemistry, and concentration of PrPsc at onset of illness. Collaborative efforts with Dr. Hood (Project II) will take full advantage of advances in the Human Genome Project for candidate gene prioritization using oligonucleotide arrays and other technologies. BAC transgenesis and gene targeting will be used for identification of these and other prion disease modifiers that will be identified. QTL analysis is dependent on naturally occurring polymorphisms between mouse strains and thus samples only a small subset of potential modifier genes. Therefore, a screen

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will be established for chemically induced mutations that alter prion incubation time in transgenic mice so that all genes potentially are targeted. Finally, in collaboration with Drs. Hood (Project 11) and Prusiner (Project III), we will identify networks that are perturbed by misexpression of the PrP-related protein Dpl and screen for modifiers of Dpl-induced phenotypes. The combination of approaches will help define the genetic bases for susceptibility to prion disease and apply this new genetic knowledge to understand the underlying molecular processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE EXPRESSION IN PEDIATRIC ARTHRITIS Principal Investigator & Institution: Glass, David N.; Professor of Pediatrics and Director; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 22-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This program project grant application focuses on the use of DNA micro array (gene chip) technology to detect differential expression of genes in children with pediatric arthritis. It builds on the existing resources and provides strong interactions and synergism with the Cincinnati Rheumatic Diseases Core Center (P30) grants in existence within the applicants' center. Rapid advances in biotechnology, including the human genome project, the advent of high through put micro arrays that contain nearly all genes in the human genome, and statistical computing power have come together to create an unprecedented opportunity to refine the diagnosis, treatment, and understanding of the pathophysiologic mechanisms involved in pediatric rheumatic diseases. Four projects are proposed. Project by Glass focuses on the recognition of disease specific gene expression profiles in peripheral blood from inception cohorts of children with either poly or pauciarticular onset juvenile rheumatoid arthritis (JRA). Prospective follow-up of these patients will reveal how gene expression patterns change with disease evolution and therapy and will provide insights into varying pathophysiological mechanisms between the two disease subtypes. Project by Hirsch will perform a comprehensive functional genomic analysis of synovium in JRA, and elucidate the molecular pathways responsible for the aggressive behavior of fibroblasts in arthritic synovium. Project by Colbert focuses on juvenile spondyloarthropathies (JSpA) and aims to determine whether expression profiles distinguish JSpA from other forms of pediatric arthritis and controls. Project by Grom will determine if expression profiles in early disease can distinguish patients with systemic JRA (sJRA) who progress to an aggressive form of articular disease from those that do not, and determine the extent of NK dysfunction early and late in the disease. In addition, expression patterns among patients with sJRA who have acute macrophage activation syndrome (MAS) will be compared to patterns obtained after resolution of MAS and among those with a history of MAS. An Administrative Unit will in conjunction with the MCRC Methods Core manage the prospective clinical studies will assure proper collection and processing of demographic and clinical phenotype data. The Administrative Unit will also provide leadership and evaluate program progress. The Tissue Core, an extension of the P30 Tissue Repository will handle biological specimens from initial acquisition through to the release to the Affymetrix Core. An Informatics Corelis proposed to manage and analyze the data in conjunction with project staff and develop a web-enabled national level genomic database. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Human Genome Project

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Project Title: GENETIC APPROACHES TO CHOLESTEROL METABOLISM IN HUMANS Principal Investigator & Institution: Hobbs, Helen H.; Professor; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant) This is a new project in which we will use the tools and information generated by the Human Genome Project to identify new genes that determine plasma levels of lipoproteins and susceptibility to atherosclerosis. This project combines all of the human genetics studies of the ongoing Program Project into a single effort. Over the last two years, we have prepared for this change by establishing the infrastructure to map genes and identify DNA sequence variations using high throughput methodologies, including genome scanning, automated DNA sequencing, variant detector arrays, and heteroduplex chromatography. By concentrating all of our human genetic studies into a single project, we will enhance our ability to discover new genes and sequence variations that determine the levels and distributions of plasma lipids in humans. Two general approaches will be taken in this project. First, we will perform linkage studies in dyslipidemic families to map and identify new genes involved in cholesterol homeostasis. The identification of genes contributing to the most common forms of hyperlipidemia has been complicated by the fact that multiple factors, both genetic and environmental, influence plasma lipoprotein levels. To circumvent this problem, we will focus our efforts on large, phenotypically well-defined families in which the segregation of dyslipidemia suggests the effect of a single major gene. Second, we will analyze the frequency of single nucleotide polymorphisms (SNPs) in wellcharacterized hyperlipidemic and normolipidemic individuals to identify sequence variations that 1) contribute to inter-individual differences in plasma lipoprotein levels in the population, and 2) confer susceptibility or resistance to accelerated coronary atherosclerosis, the most devastating consequence of dyslipidemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENOME WIDE ANALYSIS OF DNA COPY NUMBER BY ARRAY Principal Investigator & Institution: Pinkel, Daniel D.; Professor; Cancer Center; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 25-MAR-1999; Project End 29-FEB-2004 Summary: (Applicant's Description) Comparative genomic hybridization (CGH) has demonstrated its ability to provide a unique insight into the genetic abnormalities involved in the development of cancer. By co-hybridizing total genomic DNA from a specimen and from normal cells to metaphase chromosomes, it provides a genome-wide map of the DNA sequence copy number variation with cytogenetic scale resolution, - 20 Mb. Application of CGH to a wide variety of tumor types has found that most of them contain copy number changes that recurrently affect many regions of the genome, indicating the locations of known and many yet to be discovered oncogenes and tumor suppressor genes. We have recently demonstrated the feasibility of a new form of CGH that detects copy number variations comparative hybridization to a DNA microarray containing clones from any set of well mapped loci. Resolution with array CGH is more than 100 fold better than with standard CGH and the copy number variations are mapped relative to the genetic and physical maps being produced by the human genome project. We are proposing to develop a robust, flexible implementation of array CGH the human genome. This will require 1) selecting appropriate target clones with a goal of providing 1 Mb resolution (-3000 clones) throughout the genome. 2) improving

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methods for making arrays, and for acquiring and analyzing fluorescence signals. 3) improving methods for hybridization and for genomic DNA amplification to minimize the amount of specimen needed for analysis and to assure accurate results. 4) developing informatics for managing the project and displaying and analyzing the data. The project is designed so that it begins to provide useful measurement capability in its first year, and continues to improve throughout the 5 year project period. The performance of array CGH will be tested within the project as is necessary for technical development, and it will be evaluated in practice in collaboration with the national breast cancer SPORE projects. In summary, this project will develop the technology to permit human genome-wide, high throughput analysis of DNA copy number. The availability of this technique will facilitate positional cloning of cancer genes, and very large scale studies of the correlation of genetic abnormalities with biological and clinical behavior of tumors. The combination of array CGH data with data from other sources, for example microarray measurements of mRNA expression. will provide an even more powerful window on the genetic events involved in cancer development and progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENOME-WIDE ANALYSIS FOR ADDICTION SUSCEPTIBILITY GENES Principal Investigator & Institution: Lachman, Herbert M.; Psychiatry and Behavioral Scis; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 28-FEB-2006 Summary: (adapted from applicant's abstract): This is an R01 application for funding to identify chromosomal markers linked to drug dependence. The use of illicit, highly addictive drugs is a major public health and legal problem in the United States and around the world. There is an urgent need for new pharmacological treatment options. Since a substantial fraction of the vulnerability to abuse drugs has a genetic basis, determining underlying genetic factors will help identify new targets to therapeutic intervention. One approach used to identify genetic factors in complex traits is to use non-parametric linkage analysis, such as the affected sib pair method. However, it is very difficult to ascertain large numbers of sib pairs concordant for drug abuse/dependence, especially in subjects who are actively abusing hard drugs. The investigators will address this problem by ascertaining a relatively stable group of opiate dependent subjects and their affected siblings in a very large population of methadone maintenance clients. Opiate addicts enrolled in methadone programs are perhaps the most stable group of heavily addicted individuals available for clinical study, since they come to clinic almost every day to pick up methadone, and meet with counselors, social workers, psychiatrists and medical doctors frequently. From a pool of 20,000 clients, they will identify 450 sib pairs who are both being treated in a methadone program. These subjects will be assessed by SCID and various psychological measures to identify psychiatric conditions and personality and temperament traits associated with substance dependence. A two stage, genome-wide search for genetic loci linked to opiate dependence will take place; the first at a 10 centimorgan resolution. Positive markers will be followed up in a second stage, 1-3 centimorgan survey. By the end of the project, which will coincide with the completion of the human genome project, they will be able to analyze all of the specific candidate genes that map to linked markers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

20

Human Genome Project

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Project Title: GENOMIC STUDIES OF THE HUMAN Y CHROMOSOMEN Principal Investigator & Institution: Page, David C.; Professor/Investigator; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2001; Project Start 01-JAN-1991; Project End 31-DEC-2002 Summary: This project focuses on the human Y. chromosome in the context of the Human Genome Project's 5-year goals as recently stated by Collins et al. (Science 282:682-689, 1998). The principal long-term objective of this project is systematic cataloguing, and interpretation, of natural variation in genes in the NRY (the NonRecombining portion of the Y chromosome, comprising 95% of the chromosome). The NRY differs from the remainder of the nuclear genome in two respects: it is found in only one sex, and it does not participate in meiotic recombination. Thus, one might expect that variation in NRY genes would differ systematically from that on autosomes or the X chromosome. This project aims to explore this preposition in detail at the nucleotide level. The central aim of the present three-year proposal is to assembly a nearly comprehensive catalog of coding sequence variation in NRY genes. Specifically, coding sequence variants will be identified in 48 diverse Y haplotypes representing the great majority of US males. As a control for these studies of NRY genes, variants in the coding sequences of X-linked or autosomal homologs (of NRY genes) will also be catalogued. To place this survey of human sequence variation in context, parallel studies of NRY (and homologous) gene variation will be conducted in non-human primates. In collaboration with other investigations, we will systematically catalog polymorphism in human NRY gene order or copy number among the 48 Y haplotypes mentioned previously. The resulting catalog of NRY gene variation will provide a foundation for elucidating the roles of the Y chromosome in health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HUMAN GENOME EDUCATION MODEL (HUGEM) PROJECT II Principal Investigator & Institution: Lapham, E V.; Pediatrics; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2001; Project Start 28-SEP-1993; Project End 31-OCT-2001 Summary: (Applicant's abstract) The field of medical genetics continues to witness dramatic advances (largely resulting from the Human Genome Project) which have led to an increased demand for genetic services and brought genetics issues to the forefront of health care. While physicians and nurses provide primary medical care for persons with genetic conditions, the allied health professionals (such as nutritionists, occupational therapists, physical therapists, psychologists, social workers, and speechlanguage pathologists) are often the first to: 1) suspect that their clients have a genetic disorder; 2) give a label to the developmental or behavioral symptoms; 3) recommend further evaluations including genetic testing 4) interpret and discuss results of testing and sometimes give diagnoses; 5) influence attitudes and decisions of their clients about participating in genetic testing or research; 6) provide referrals to other resources such as genetic counseling and genetic support groups; 7) provide counseling related to coping with and adjusting to a genetic condition; and, 9) educate the public about genetic conditions and ELSI issues. Allied health professionals, in general, remain inadequately informed in the area of human genetics and issues related to genetic knowledge, genetic testing, and genetic research. Building on the experiences and products of the Human Genome Education Model Project (1993-1997), Georgetown University Child Development Center-University Affiliated Program (UAP) (Dept. of Pediatrics) and the Alliance of Genetic Support Groups plan to use the collaborative

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(consumer and health professional) education model to educate allied health professionals through their respective national organizations (American Dietetic Association, American Occupational Therapy Association, American Physical Therapy Association, American Speech-Language-Hearing Association, American Psychological Association, Council on Social Work Education, and National Association of Social Workers). The overall goal is to derive optimal benefit from development of the Human Genome Project for allied health professionals and the consumers they serve. The specific aims are: 1. to conduct surveys to assess needs, determine education priorities, and identify resources of the respective organizations; 2. to use information from the surveys to adapt the collaborative education model to educate and sensitize health professionals about genetics, the HGP and its ELSI issues and to implement education for national staff, practitioners, and educators; and 3) to evaluate each level of education and disseminate information about the project. HuGEM II is designed to be carried out over a three-year period. An advisory committee will provide expertise in medical genetics, ethics, law, consumer issues, social policy, and health education. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN GENOME PROJECT AND COMPARATIVE GENOMICS Principal Investigator & Institution: Haussler, David H.; Professor; University of California Santa Cruz 1156 High St Santa Cruz, Ca 95064 Timing: Fiscal Year 2001; Project Start 12-JUL-2001; Project End 30-JUN-2006 Summary: We plan to provide bioinformatics support to the Human Genome Project, and work with the Whitehead Institute for Biomedical Research/MIT Center for Genome Research on comparisons between human and other vertebrate genomes. We will continue to supply monthly assemblies on the currently available human genome sequence, which we have provided since May 20000. Along with each assembly we will provide an integrated database of links to ESTs, mRNAs, SNPs, gene predictions, markers, isochores, contigs, gaps, clones, and homologies with other vertebrates, mapped to specific positions on the assembled genome and viewable side-by-side on the web through an interactive browser. This web browser will facilitate the use of the primary working draft and finished human genome data, stored by NCBI and EBI, by medical and scientific researchers worldwide. In addition to our support role, we propose to develop new methods to use comparative genomics, computational algorithms, and microarray technology to uncover the structure and function of human genes. Sequence homologies with the genes of other vertebrates, combined with EST and mRNA data, will be used to determine gene structure, alternative splicing, and regulatory motifs for human genes. Custom microarrays will be built with specific oligos designed to confirm splicing and regulation for the most medically important genes. Hidden Markov models will be built to model the domain structure of the protein products, and suggest functional classification by homology. Expression data will be combined with predicted structural features and data from external sources to produce the most comprehensive computational and experimental classification possible. The centerpiece of the proposal is a 1000 CPU computer cluster, funded jointly by Howard Hughes Medical Institute and through this award from NHGRI, which will enable us to perform the necessary genome-wide computations. Funding from the Sloan Foundation and internal funding from the UCSC campus will also provide support for the development of M.S. and Ph.D. programs in bioinformatics. The other financial component of the proposal is for staff and student support. By focusing funds from several sources, we are able to train a new generation of scientists, explore new research methodologies, and provide a vital service for the Human Genome Project.

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Human Genome Project

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFO CONFERENCE - MINORITIES ON THE HUMAN GENOME PROJECT Principal Investigator & Institution: Malvern, Kathryn T.; Zeta National Educational Foundation 1734 New Hampshire Ave Nw Washington, Dc 20009 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2004 Summary: (provided by applicant): This project is an Information Conference for Minorities on the Human Genome Project: The Challenges and Impact of Human Genome Research for Minority Communities. The two-day conference is designed primarily for representatives from the minority communities (African-Americans, Hispanics, Asian Americans, Native Americans), but will be open to all interested persons. Outreach for conference attendance will be targeted to minority community leaders, community organizations, churches, educators, government officials, fraternal groups, civic and social groups, business and professional organizations, and health care organizations. The project's broad objective is to raise the level of awareness in minority communities of the rapid strides being made in human genome research, and the potential and value to minorities, particularly with respect to health care; to identify issues that are important to the minority communities and avenues for more involvement of these communities; and to explore post-conference ways of continuing input. Through presentations, workshops and open discussions, the conference will address the ethical, legal and social issues raised by human genome research developments; the impact on treatments for health problems such as sickle cell anemia, cancer and other physical and mental health concerns. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFRASTRUCTURE FOR MULTI-CELLULAR HUMAN METABOLIC MODELS Principal Investigator & Institution: Schilling, Christophe H.; Genomatica 5405 Morehouse Dr, Ste 350 San Diego, Ca 92121 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-MAR-2004 Summary: (provided by applicant): With the completion of the human genome project and recent advances in high throughput technologies, much of the ongoing effort is now to find all the functional elements on the sequence and to create computational tools to analyze and interpret the large volume of data available. This overwhelming amount of information together with the complexity of biological systems has created a need for in silico modeling and the development of model-driven systems biology. The reconstruction of the reaction networks that these components form allows for the formulation of in silico models. Investing on our success in modeling microbial cells using constraints-based approach, we intend to assess the scientific and computational feasibility of building the first genome-scale metabolic model for human cells. We will build two cell-specific metabolic models, test and characterize them, and define the issues associated with building multi-cellular metabolic models. Given the prevalence of metabolic involvement in human disease, this effort is both timely and of great significance. The integration of the sequence annotation, the association relationships for splice variants, data representation and computational issues will be addressed at the completion of this project. Success of this proposal would build the foundation for the development of a comprehensive model of human metabolism that would be extremely

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valuable for drug discovery and development efforts and has the potential to drive the process of therapeutic research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTEGRATED DNA SEQUENCING SYSTEM Principal Investigator & Institution: Jovanovich, Stevan B.; Vice President; Molecular Dynamics, Inc. 928 E Arques Ave Sunnyvale, Ca 94085 Timing: Fiscal Year 2001; Project Start 20-JUN-2000; Project End 30-JUN-2003 Summary: (Applicant's Abstract) The Human Genome Project is rapidly developing a draft consensus sequence of the Human Genome. The immense value of this information has triggered the scale up of production rates and the incorporation of highthroughput capillary-array electrophoresis instruments. Further improvements are needed to decrease sample costs, increase automation, and improve throughput rates. This project will create an automated, integrated DNA analysis system that prepares nanoliter (nL)-scale sequencing reactions and analyzes the reactions in an ultrahighthroughput, microchip-based DNA sequencer. The integrated system will consume about one-hundredth of the reagents used today and have a ten-fold higher throughput rate. The integrated system will consist of two main modules, a sample preparation module and an ultrahigh-throughput DNA analysis module. The sample preparation module will use arrays of 384 capillaries in \cassettes to move liquids and perform biochemical reactions in 125 nL volumes. This module will automate shotgun sequencing beginning with lysed clones to produce fluorescently labeled cycle sequencing reactions for capillary or microchip analysis. The microchip-based DNA analysis module will load, run, and detect DNA samples in microchannels for sequencing and genotyping. This module will use robotics to transfer samples from microtiter plates to sample loading ports on a microchip, dock the microchip with electrodes under a detector, inject samples and separate them. The two modules will be developed simultaneously and then integrated into a complete automated sequencing system. The project will develop a series of prototypes that will be alpha-tested in the Molecular Dynamics Production Sequencing Group and then beta-tested at our collaborators at the Joint Genome Institute, the Washington University Genome Sequencing Center, and the Macromolecular Analysis Facility at the University of Wisconsin-Madison. The results of the external testing will be used to verify the system performance, refine the prototypes, and streamline the integration of this new technology into genome centers and core facilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ISOLATION OF CDNAS FOR PROTEIN INTERACTION NETWORKS Principal Investigator & Institution: Finley, Russell L.; Assistant Professor; Genetics; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-MAR-1996; Project End 31-DEC-2001 Summary: One approach to the National Human Genome Project goal of identifying all human genes has been to isolate and sequence expressed sequences or cDNAs. The cDNAs have generally been isolated on the basis of their expression in a particular tissue, or their differential expression in one setting and not another, but not on the basis of functional characteristics. Over time, this approach will undoubtedly yield significant new insights into gene function. Initially , however, this endeavor will only provide the sequence of each new gene. A more traditional approach, ongoing for years in many laboratories, has been to identify one or a small set of genes presumed to be involved in

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Human Genome Project

a specific cellular process, and then to invest the necessary, and often considerable, time characterizing their function in normal and disease states. In contrast to the goals of the Genome Project., this approach identifies new genes slowly. In the project proposed here, new cDNAs will be rapidly and successively isolated using a technique that will provide information about the function of each encoded protein. Because many regulatory processes in a cell are controlled by networks of interacting proteins, new cDNAs that encode the members of these networks will be isolated based on proteinprotein interactions. An efficient two-hybrid system will be used repeatedly to isolate new cDNAs that encode the members of these networks will be isolate new cDNAs based on the ability of their encoded proteins to interact with other proteins. Beginning with a small set of proteins thought to function in protein interaction networks, new cDNAs will then be used in subsequent hunts to find other new cDNAs, and this process will be continued to isolate cDNAs for all of th members of a network. The method will provide the new cDNAs in a form that can be readily characterized by sequencing, and by testing whether the encoded proteins can interact with any members of a panel of 400 known proteins using a rapid interaction mating assay. This information networks they belong to. The approach provides a way to rapidly identify large numbers of new cDNAs such as those identified in the Genome Project. The efficiency of the method proposed will allow over 1000 cDNAs to be isolated and characterized in this way by one full-time and one part-time worker. Moreover, during the initial phase of this project, the feasibility of scaling-up the method further will be explored. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LEARNING ABOUT RESEARCH IN NORTH CAROLINA (LEARN) Principal Investigator & Institution: Corbie-Smith, Giselle; Assistant Professor of Medicine; Sheps Center for Hlth Serv Res; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 13-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): As the Human Genome Project develops beyond the mapping and sequencing of the human genome to a tool for understanding genetic variation, gene-environment interaction and disease expression, the need for a large and diverse group of research participants is critical. Yet, populations that suffer the consequences of health disparities may be difficult to recruit into research studies because of distrust and concerns about the motives of researchers, themes that may be amplified in genetic research. The proposed study, Project LeARN (Learning About Research in North Carolina), will build on a series of well established population based studies of the genetic, environmental and behavioral predictors of colorectal cancer among African American and white cases and controls, the North Carolina Colorectal Cancer Study (NCCCS), to understand participants' views of genetic variation research. Project LEARN contains both a longitudinal component to assess change in beliefs about causality as a result of participation in NCCCS, and a cross-sectional component to examine NCCCS participants' motivations, assessment of positives and negatives and understanding of genetic variation research. The proposed study will survey 832 NCCCS study participants with the following specific aims, to describe: 1) NCCCS participants' perceptions of causality of colorectal cancer and how perceptions of causality of colorectal cancer change after participation in the NCCCS determinants of colorectal cancer interview; 2) what motivates research participants to participate in the NCCCS study; 3) NCCCS participants' perceptions of positives and negatives related to collecting genetic data in epidemiologic research; and 4) how NCCCS research

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participants understand the purpose of the NCCCS research. All aims will be examined for differences by disease status and race/ethnicity. The proposed research is significant in that it is directly responsive to RFA-HG-02-003; involves a population-based examination of lay perceptions, interpretations, and concerns about genetic variation research; and includes participants actually involved in such research. The proposed research will fill a significant gap in the current understanding of how research participants view genetic variation research. Such information should enable development of more effective strategies for increasing the potential benefits of genetic variation research, while at the same time reducing the potential risks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METHOD FOR GLOBAL AND TARGETED DISCOVERY OF SNP MARKERS Principal Investigator & Institution: Kwok, Pui-Yan; Professor of Dermatology; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2002 Summary: (Applicant's abstract) To accomplish the stated goals of the Human Genome Project and to reap the fruits of this major undertaking, the complete sequence of a composite human genome will have to be deciphered by the year 2005 and a genetic map composed of a dense set of single nucleotide polymorphism markers must be developed for complex genetic trait analysis. There is general agreement that the technology is in place for large-scale sequencing but that sequence- ready large-insert clone retrieval will soon become the bottleneck in any significant large-scale sequencing project. Similarly, a new NHGRI initiative will undoubtedly lead to the development of a dense set of SNP markers for the human genome but it is unclear how one can best utilize these markers in population studies that require genotyping thousands of individuals with thousands of markers. In this proposal, we plan to develop two simple, flexible, homogeneous methods for DNA analysis based on fluorescence polarization detection. Specifically, we aim to (1) develop a four-color DNA genotyping method based on fluorescence polarization detection and primer extension reactions; (2) develop a multi-color PCR detection method based on fluorescence polarization detection and the 5'-nuclease "TaqMan" assay for both library screening and for allelic discrimination. Once developed, these methods will facilitate clone recovery for sequencing projects and for flexible SNP genotyping in population studies. As such, they will help define the genetic factors associated with common diseases with complex inheritance patterns and the relationship between genetic and environmental influences on human health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICROARRAY ANALYSIS OF ALTERNATIVE SPLICING AND DISEASE Principal Investigator & Institution: Ares, Manuel J.; Profesor and Chair; University of California Santa Cruz 1156 High St Santa Cruz, Ca 95064 Timing: Fiscal Year 2001; Project Start 12-JUL-2001; Project End 30-JUN-2006 Summary: We plan to provide bioinformatics support to the Human Genome Project, and work with the Whitehead Institute for Biomedical Research/MIT Center for Gene Research on comparisons between human and other vertebrate genomes. We will continue to supply monthly assemblies of the currently available human genome sequence, which we have provided since May 2000. Along with each assembly we will

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provide an integrated database of links to ESTs, mRNAs, SNPs, gene predictions, markers, isochores, contigs, gaps, clones, and homologies with other vertebrates, mapped to specific positions on the assembled genome and viewable side-by-side on the web through an interactive browser. This web browser will facilitate the use of the primary working draft and finished human genome data, stored by NCI and EBI, by medical and scientific worldwide. In addition to our support role, we propose to develop new methods to use comparative genomics, computational algorithms, and microarray to uncover the structure and function of human genes. Sequence homologies with the genes of other vertebrates, combined with EST and mRNA data, will be used to determine gene structure, alternative splicing, and regulatory motifs for human genes. Custom microarrays will be built with specific oligos designed to confirm splicing and regulation for the most medically important genes. Hidden Markov models will be built to model the domain structure of the protein products, and suggest functional classification by homology. Expression data will be combined with predicted structural features and data from external sources to produce the most comprehensive computational and experimental classification possible. The centerpiece of the proposal is a 1000 CPU computer cluster, funded jointly by Howard Hughes Medical Institute and through this award from NHGRI, which will enable us to perform the necessary genome-wide computations. Funding from the Sloan Foundation and internal funding from the UCSC campus will also provide support for the development of M.S. and Ph.D. programs in bioinformatics. The other financial component of the proposal is for staff and student support. By focusing funds from several sources, we are able to train a new generation of scientists, explore new research methodologies, and provide a vital service for the Human Genome Project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR ALTERATIONS IN LUNG CARCINOGENESIS Principal Investigator & Institution: Mao, Li; Associate Professor/Director; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 20-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Early lung tumorigenesis is poorly understood at the molecular level. Consequently, no validated molecular marker is currently available for lung cancer risk assessment or evaluation of therapeutic efficacy. We previously demonstrated that certain genetic alterations commonly found in lung cancers might occur in normal-appearing bronchial epithelium of smokers. Altered expression patterns of tumor suppressor genes/oncogenes could also be detected in the bronchial epithelium of smokers. Recently, we found that DNA methylation status in promoter regions of genes involved in tumorigenesis could be altered, not only in lung tumors but also in the bronchial cells of smokers without cancer, resulting in transcriptional repression or activation of these genes. Recent advances in human genome project and high-throughput technologies provide opportunity to accelerate discovery of biomarkers for cancer risk assessment and evaluation of therapeutic efficacy. We hypothesize that substantial molecular alterations occur in airway of smokers, which causes "field defect" and associates with an increased lung cancer risk in this population. As a result, these molecular alterations critical in the initiation of transformation and early progression may predict lung cancer risk and can be used as intermediate endpoints to assess efficacy of chemopreventive agents. Three specific aims are proposed: (1) To identify molecular alterations in smoking damaged lungs and determine their role in assessing efficacy of chemopreventive agents. We will focus on molecular abnormalities that involve critical pathways and can be frequently detected in

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the bronchial epithelial cells in smokers. Potential differences between current and former smokers will also be analyzed. (2) To determine the role of easily accessible tissues as surrogate materials in evaluating lung damages and chemopreventive effects in the lung. We will determine molecular alterations in sputum and oral brushes in smokers and more importantly to see if potential drug effects in these specimens may reflect those in lung bronchial epithelium. (3) To identify novel biomarkers for risk assessment and evaluation of effects of chemoprevention. In this exploratory aim, we will identify proteins abnormally expressed in carcinogen damaged lungs with high risk to develop lung cancer as well as proteins modulated by chemopreventive agents. We believe that the success of this project will significantly improve our understanding of early lung carcinogenesis at the molecular level and provide useful molecular markers for lung chemoprevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETIC EPIDEMIOLOGY STUDY OF ADHD/DRD4 Principal Investigator & Institution: Moyzis, Robert K.; Professor; Biological Chemistry; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2001; Project Start 20-JUL-2000; Project End 30-JUN-2003 Summary: Utilizing the vast number of marker loci being identified by the Human Genome Project, association studies are being applied to data on many complex disorders. Once an association is identified the issue for investigators is to determine what the association tells us about the disease process. When confirmed by numerous studies, the possibility of he association being a statistical artifact is remote. We are then left with two explanations: the associated allele plays a causative role in the disorder or the allele is in linkage disequilibrium with another locus(polymorphism) which does play a role. In order to truly understand the disorder we will have to distinguish between these, but how? This project is designed to capitalize on our ability to rapidly and accurately sequence DNA for a locus over a large number of individuals ascertained within a rigorous research design, and apply that information to determine the reason for he association. We have chosen to examine Attention Deficit Hyperactivity Disorder (ADHD) and the dopamine receptor gene DRD4. We first reported the association of ADHD with the D4.7 allele of this gene, which has now been confirmed by us and five other studies. ADHD affects about 3-5% of the school-aged population and is considered the most prevalent psychiatric disorder of childhood. Family, twin, and adoption studies have established a strong genetic basis for ADHD. Initial molecular genetic investigations of candidate genes focused on the neurotransmitter dopamine because most patients are responsive to methylphenidate. The DRD4 locus is a highly variable locus where the 7- repeat form of a 48 bp segment occurs in many allelic forms. Other polymorphisms have been identified in DRD4, some of which have known functional significance, but none of which have been evaluated in ADHD studies. Probands will be ascertained through clinical trials at the Child Development Center, UCI when they meet rigorous diagnostic criteria for ADHD. Probands, their parents, and siblings will be studied and their DNA sequenced for DRD4. Other dopamine pathway loci will be genotyped. Within those families who carry D4.7 we will determine the haplotype(s) present in affected individuals for all of the polymorphisms present in the DRD4 gene. For the non-D4.7 families we will test or tight linkage with the DRD4 region. If D4.7 is merely a marker in linkage disequilibrium with a causative polymorphism, then this latter subset of families should also show evidence for linkage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR GENETICS OF FAMILIAL LARYNGEAL PARALYSIS Principal Investigator & Institution: Manaligod, Jose M.; Assistant Professor; Otolaryngology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Laryngeal paralysis is a frequent cause of stridor and airway obstruction in infants, often requiring tracheostomy or other surgical procedures to provide an adequate airway. Hereditary forms of laryngeal paralysis have been described, indicating that genetic factors may be a primary cause of certain cases. The long term objective of this study is to identify the role of genetic mechanisms in laryngeal paralysis. The hypothesis to be tested is that genetic mutations cause familial laryngeal abductor paralysis (FLAP). The specific aims of this project are: 1) To identify genetic loci linked to FLAP- Genetic linkage analysis of families in which FLAP segregates is accomplished by PCR-based screening with a short tandem repeat polymorphism (STRP) panel that covers the entire human genome. This is confirmed by statistical analysis using the LOD score method and the computer programs, SLINK, LINKAGE 5.1 and HOMOG. 2) To identify candidate genes in the chromosomal region(s) linked to FLAP- known and predicted genes are identified within FLAP genetic region(s) by sequence analysis of data from the Human Genome Project. Positional candidate genes are prioritized for mutation screening according to gene expression and function that appear consistent with the FLAP phenotype and its possible disease mechanisms. 3) To identify FLAP-causing genes- Single strand conformation polymorphism (SSCP) gel analysis and direct sequencing are used to screen genomic DNA for FLAP-causing mutations. Detected mutations are further analyzed by population screening, computer analysis of the mutated sequence, and tissue in situ hybridization studies to determine the likelihood that a specific genetic mutation causes FLAP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR GENETICS OF SCHIZOPHRENIA LOCUS ON 1Q21-22 Principal Investigator & Institution: Brzustowicz, Linda M.; Associate Professor; Biological Sciences; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: (Investigator's Abstract): Schizophrenia is a serious neuropsychiatric illness estimated to affect 1.3 percent of the adult population in the United States. Family, twin and adoption studies have demonstrated that schizophrenia is predominantly genetic, with a high heritability. The complex genetics, phenotypic uncertainty, and unclear role of environmental interactions have led to the discouraged view that significant genetic linkage will not be easily obtained. None of the linkage reports published to date detail a finding of significant magnitude to serve as a starting point for positional cloning. We have recently concluded a genome-wide search for loci contributing to risk for schizophrenia, and multipoint analysis with markers from 1q21-22 have produced a maximum LOD score of 6.50 between the markers D1S1653 and D1S1679, with an estimated 75 percent of families linked to this locus. Further mapping has reduced the interval containing this gene to less than 2 Mb. We propose a project to develop a dense map of polymorphic markers within this currently defined minimum genetic region, for use in crossover and linkage disequilibrium analyses to further narrow the region containing the gene. Using sequence data from the Human Genome Project, we then plan to identify a comprehensive list of gene in the new minimum genetic region and

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systematically screen them for mutations using temperature gradient gel electrophoresis on a sample of subjects with very high (greater than 95 percent) conditional probability of linkage to 1Q21-22. Simulation studies suggest that we will have sufficient power to identify the true susceptibility gene. We plan to screen this gene for mutations in the remainder of our linkage sample and in the schizophrenia subjects in the NIMH Center for Genetics Studies sample. The identification of a gene involved in schizophrenia susceptibility will allow insight into the earliest genesis of this debilitating illness. Screening for mutations in this gene in larger, unrelated samples will allow for an estimate of the prevalence of the effect of this locus in the general population. Controlling for the effects of this gene in genetic linkage studies should increase the power to identify other susceptibility loci. Unraveling the genetics of this complex disorder will also facilitate the investigation of the environmental triggers of disease expression, and could ultimately lead to strategies to prevent the onset of clinical symptoms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBIOLOGY AND GENETICS OF AUTISM Principal Investigator & Institution: Spence, M Anne.; Professor; Pediatrics; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 28-FEB-2003 Summary: Despite years of research efforts, there is little understanding of the etiology or pathophysiology of Autistic Disorder (AD) and no treatment. Three significant developments have raised the possibility that progress can be made in unraveling the mysteries of AD: (1) morphometric analyses using MERI have shown that the brains of AD children ar larger in volume with significant differences in white matter, (2) the POMC pathway compounds B-endorphin and ACTH respond and interact differently before and after challenge in some children with AD and (3) the Human Genome Project has provided ahead of schedule a dense map of the human genome including about half of the expressed genes (ESTs). The observation that the brains of AD children are larger than normal controls has been documented by several research teams. This enlargement is localized to white matter and to the association regions of the brain. Can these findings be replicated in a newly-recruited cohort of late childhood children with AD? Using sequential MRI scan, can the effects of puberty on brain development in AD be defined? Are these findings consistent across the entire sample of AD children? Project 2: MRI is addressing these points. The observation that some children lose skills, social and/or verbal in the early course of AD is an anecdotal but consistent finding. Do these children have normal development and regress? Does a Full Autistic Regression exist separate from a Language-Only Regression? Does the neurobiological train from the MRI study differentiate these AD children with regression? Project 3: Regression will investigate a group of very young AD children and answer these questions about Autistic Regression. The first two new developments are from studies by researchers at UCI. Both the MRI and opiate findings could represent genetics differences between AD and normal children and/or within this group of children diagnosed as AD. Using the Human Genome framework and the genetic analysis expertise at UCI we can ask specifically if neurobiological differences represent the action of genes contributing to AD (several studies estimate the number of AD loci is 3-6). Are some of these half-dozen loci represented by the phenotypes of brain size? Are some of these half-dozen loci represented by the phenotypic characteristic of Autistic Regression subtypes? Project 1: Genetics is designed to answer this question. For AD, where we known so little by the underlying biology, it is essential that we pursue clues in a systematic fashion, using the

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Human Genome Project

state of our genetic knowledge as a tool. Our research provides clues on where to begin the genetics search. This grant is designed to exploit those clues to the fullest. It is unlikely that all cases, or even a large proportion of cases, of AD are purely genetic. But some AD surely is genetic, and finding those genes constitutes a critical first step towards understanding this disastrous disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETECTION

NOVEL

MICROARRAY

FOR

SNP

AND

METHYLATION

Principal Investigator & Institution: Meng, Fan; Co-Director; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-AUG-2003 Summary: (Applicant's Abstract): The main goal of this proposal is to develop new microarray-based high throughput single nucleotide polymorphism (SNP) analysis methods for the purpose of studying quantitative genetic factors underlying complex behaviors and diseases, such as individual's vulnerability for drug abuse and mental illness. Genome-wide SNP scanning has the potential to isolate the quantitative trait loci involved in complex disorders. It was estimated that a genomic region that contributes 5 percent or more to a disease could be localized to a 3 kb sequence with a SNP association analysis involving 500 individuals and 500,000 SNP markers across the whole genome. Since the Human Genome Project will soon generate the complete human genome sequence, and there are various public and private efforts to develop high-density human SNP markers, the framework required for genome-wide SNP scanning will quickly be established. However, none of the currently available SNP analysis methods can deal with such genome-wide high-density SNP scanning projects in a timely and cost-efficient manner. The proposed project aims to increase the output of a single operator to 400,000 SNP analysis per day using standard microarray laboratory equipment. The cost of SNP analysis for large-scale projects will also be reduced to around $0.01 for each SNP marker, with the exact cost depending on oligo synthesis. These goals represent an order of magnitude improvement over currently SNP analysis methods in both speed and cost. Foreseeable improvements in these methods have the potential of another 10-fold increase in throughput and further cost reduction. The new microarray array formats presented in this proposal will also be applied to a wide range of problems in functional genomics such as genomic DNA methylation analysis and differential display. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREDICTING PROTEIN FUNCTION FROM STRUCTURE Principal Investigator & Institution: Gregoret, Lydia M.; University of California Santa Cruz 1156 High St Santa Cruz, Ca 95064 Timing: Fiscal Year 2001; Project Start 12-JUL-2001; Project End 30-JUN-2006 Summary: We plan to provide bioinformatics support to the Human Genome Project, and work with the Whitehead Institute for Biomedical Research/MIT Center for Genome Research on comparisons between human and other vertebrate genomes. We will continue to supply monthly assemblies of the currently available human genome sequence, which we have provided since May 2000. Along with each assembly we will provide an integrated database of links to ESTs, mRNAs, SNPs, gene predictions, markers, isochores, contigs, gaps, clones, and homologies with other vertebrates, mapped to specific positions on the assembled genome and viewable side-by-side on the

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web through an interactive browser. This web browser will facilitate the use of the primary working draft and finished human genome data, stored by NCBI and EBI, by medical and scientific researchers worldwide. In addition to our support role, we propose to develop new methods to use comparative genomics, computational algorithms, and microarray technology to uncover the structure and function of human genes. Sequence homologies with the genes of other vertebrates, combined with EST and mRNA data, will be used to determine gene structure, alternative splicing, and regulatory motifs for human genes. Custom microarrays will be built with specific oligos designed to confirm splicing and regulation for the most medically important genes. Hidden Markov models will be built to model the domain structure of the protein products, and suggest functional classification by homology. Expression data will be combined with predicted structural features and data from external sources to produce the most comprehensive computational and experimental classification possible. The centerpiece of the proposal is a 1000 CPU computer cluster, funded jointly by Howard Hughes Medical Institute and through this award from NHGRI, which will enable us to perform the necessary genome-wide computations. Funding from the Sloan Foundation and internal funding from the UCSC campus will also provide support for the development of M.S. and Ph.D. programs in bioinformatics. The other financial component of the proposal is for staff and student support. By focusing funds from several sources, we are able to train a new generation of scientists, explore new research, and provide a vital service for the Human Genome Project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREDICTING PROTEIN STRUCTURE FROM SEQUENCE Principal Investigator & Institution: Karplus, Kevin; Professor; University of California Santa Cruz 1156 High St Santa Cruz, Ca 95064 Timing: Fiscal Year 2001; Project Start 12-JUL-2001; Project End 30-JUN-2006 Summary: We plan to provide bioinformatics support to the Human Genome Project, and work with the Whitehead Institute for Biomedical Research/MIT Center for Genome Research on comparisons between human and other vertebrate genomes. We will continue to supply monthly assemblies of the currently available human genome sequence, which we have provided since May 2000. Along with each assembly we will provide an integrated database of links to ESTs, mRNAs, SNPs, gene predictions, markers, isochores, contigs, gaps, clones, and homologies with other vertebrates, mapped to specific positions on the assembled genome and viewable side-by-side on the web through an interactive browser. This web browser will facilitate the use of the primary working draft and finished human genome data, stored by NCBI and EBI, by medical and scientific researchers worldwide. In addition to our support role, we propose to develop new methods to use comparative genomics, computational algorithms, and microarray technology to uncover the structure and function of human genes. Sequence homologies algorithms, and microarray technology to uncover the structure and function of human genes. Sequence homologies with the genes of other vertebrates, combined with EST and mRNA data, will be used to determine gene structure, alternative splicing, and regulatory motifs for human genes. Custom microarrays will be built with specific oligos designed to confirm splicing and regulation for the most medically important genes. Hidden Markov models will be built to model the domain structure of the protein products, and suggest functional classification by homology. Expression data will be combined with predicted structural features and data from external sources to produce the most comprehensive computational and experimental classification possible. The centerpiece of the proposal

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Human Genome Project

is a 1000 CPU computer cluster, funded jointly by Howard Hughes Medical Institute and through this award from NHGRI, which will enable us to perform the necessary genome-wide computations. Funding from the Sloan Foundation and internal funding from the UCSC campus will also provide support for the development of M.S. and Ph.D. programs in bioinformatics. The other financial component of the proposal is for staff and student support. By focusing funds from several sources, we are able to train a new generation of scientists, explore new research methodologies, and provide a vital service for the Human Genome Project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROBLEM-BASED ELSI/GENETICS

LEARNING

UNIT

FOR

TEACHING

Principal Investigator & Institution: Markowitz, Dina G.; Director; Environmental Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 30-JUN-2006 Summary: (provided by applicant): This project will advance the level of genetic literacy in science teachers through the development and dissemination of a curriculum unit for teaching ELSI/genetics. Professional development workshops for biology teachers will provide them with a problem-based learning unit and associated classroom resources that focus on critical thinking skills pertaining to ELSI and the Human Genome Project. Hands-on activities related to modem genetic technology and the Human Genome Project will be incorporated in this curriculum unit. This curricula will be disseminated to science teachers throughout New York State via a Biology-Chemistry Mentor Network. The key features of our proposal are: - Curricula will be developed combining problem-based learning and hands-on activities relating to ELSI/genetics - The curricula will be disseminated through the New York State Biology-Chemistry Mentor network The project design team will consist of master teachers, curriculum development specialists, teacher educators, scientists, a bio-ethicist, and a pediatric geneticist - All curricula will align with New York State science education standards and will meet specific core curriculum requirements for the Living Environment course, which is taken by all students in New York State. - Teacher workshops will focus on specific ELSI, genetic principles and modem genetic technology that will be taught in high school. Teacher participants will be assessed by their changes in knowledge, attitudes, beliefs and skills as an indicator of changes in genetic/ELSI literacy. - Program evaluation will provide continual feedback as the curricula are developed, piloted, refined, and disseminated throughout New York State. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGRAM PROJECT IN THE GENETICS OF SLE Principal Investigator & Institution: Kimberly, Robert P.; Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Epidemiologic studies strongly support a genetic basis for susceptibility to human SLE, and genetically-defined murine models of systemic lupus indicate that lupus is a complex, polygenic disease with a threshold liability for inheritance. These studies in "lupus-like" mice suggest that different genes may control different aspects of the autoimmune phenotype. Most importantly, these studies, coupled with the rapid advances in knowledge available through the human genome project, underscore the feasibility of using the tools of modem genetics in

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defining human disease susceptibility and severity. The approach to the genetics of human SLE requires a multidisciplinary, team effort. Within this Program Project, we have assembled a unique and exceptionally strong multidisciplinary team, which leverages both fundamental and clinical investigations in SLE at the host institution and at the partner institutions. Our team expertise includes mastery of the theory and techniques of modem genetic mapping (linkage and association), full appreciation of the SLE clinical phenotypes and the proven ability to recruit and maintain cohorts of SLE patients (multiplex families, simplex families, case-control and longitudinal cohorts). Uniting this expertise is a broad appreciation for the pathophysiological processes in SLE in order to facilitate the selection of candidate genes and to translate findings into meaningful, mechanism-based clinical intervention. Through our team effort, we have an unprecedented power to accelerate the pace of discovery, to replicate and narrow regions of linkage, to pursue the structure and biology of candidate genes, and to test the relevance of these discoveries to clinical phenotype in a very large, meticulously studied cohort of SLE patients. Our efforts will advance our understanding of SLE and leverage both the application of current therapy and the development of new, mechanism-based therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PSYCHOSOCIAL AND ETHICAL LITERATURE IN CANCER GENETICS Principal Investigator & Institution: Patenaude, Andrea F.; Director; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 29-SEP-2004 Summary: (provided by applicant): This application proposes the preparation of a definitive book on state-of-the art psychosocial research and ethical writing and policy relating to cancer genetics and genetic testing for cancer genes. One decade after the initiation of the Ethical, Legal, and Social Implications Program of the Human Genome and the start of the modem era in cancer genetics, this book will summarize and critique existing social science and medical literature to try to answer important questions about the human impact of genetic technology. Advances in genetics promise to catalyze a fundamental change in the practice of medicine. Genetic advances have led to new approaches to the assessment of cancer risk. The coming decades will see an explosion of information about the hereditary nature of disease susceptibility. From its inception, the Human Genome Project has recognized the enormous social ramifications of decoding the human genome. Early indications arc strong that psychosocial factors play a major role in attitudes towards and utilization of genetic technology. Social science research can provide data on which to base development of interventions to maximize the benefits of genetic research. It is crucial, however, that such interventions consider also the ethical aspects of human use of genetic technology. The goals of this project are: 1) To summarize and critique the literature from a broad spectrum of social science and genetic disciplines related to psychosocial and ethical aspects of cancer genetic testing, 2.) To make the area of psychosocial and ethical aspects of cancer genetics more approachable to new/young social science investigators, 3.) To create links and encourage future collaborative research between social scientists working in genetic testing and social scientists with specialties in relevant related areas, 4.) To encourage awareness of the work of international social scientists with regard to psychosocial aspects of cancer genetic testing, and 5.) To encourage translational integration of psychosocial research findings into the development of cancer genetics programs

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Human Genome Project

through the provision of accessible summaries of psychosocial and ethical literature for use by medical and genetic professionals who are establishing cancer genetics programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUALITY OF COMMUNICATION AFTER NEWBORN GENETIC SCREENING Principal Investigator & Institution: Farrell, Michael H.; Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Background: Newborn screening tests identify congenital diseases such as Cystic Fibrosis (CF) and Sickle Cell Hemoglobinopathy (SCH) early, but ethical concerns about comprehension and psychosocial complications ("outcomes") after heterozygous results may delay implementation of new test technologies such as from the Human Genome Project. Physicians' limited genetic knowledge and communication skills may lead to disparities in communication outcomes, especially in families with socioeconomic barriers or limited access to care. Ethics research projects should study communication services during the design of systematic programs to assess and improve communication "quality" and "outcomes" on a population scale. Specific Aims: (1) To identify attitudes and expectations for communication services among parents after positive newborn screening for CF or SCH. (2) To evaluate communication quality/competence of pediatricians before and after a randomized trial of an audit-and-feedback-style communication quality assurance intervention. (3) To identify incidence and risk factors for adverse communication outcomes after screening for CF/SCH, and determine whether feedback/support to physicians will improve outcomes. Setting/Participants: Parents of infants in New York and Wisconsin with positive screens for CF/SCH. Research Plan: The project will include (1) a targeted focus group study of parents' attitudes about communication services after newborn screening, (2) a telephone study to assess (audit) communication quality/competence and give feedback to physicians, and (3) a survey of parents of CFand SCH-heterozygous infants to determine risk factors for poor comprehension and psychosocial outcomes. Career Development Plan: The principal investigator's goal is to become an independent investigator, focusing on ways to assess and improve the quality and outcomes of communication after newborn genetic screening. He will work closely with a team of mentors, advisors, and collaborators, and pursue a master's degree in Communication Sciences and a Certificate in Bioethics. Significance: It is hypothesized that communication quality/competence and outcomes vary greatly after newborn screening, but can be improved by audit and feedback. Progress in this area will generalize to other areas of communication and help streamline the implementation of new genetic testing technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RESEARCH REMODELING

FACILITIES

IMPROVEMENT

PROGRAM

AND

Principal Investigator & Institution: Kedes, Laurence H.; Chairman and Professor; Institute for Genetic Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 1999; Project Start 30-SEP-1999; Project End 30-JUN-2004 Summary: Funds are requested for partial support of a project to build out uninhabitable shell space within the University of Southern California Institute for

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Genetic Medicine (IGM) in order to consolidate and expand the activities of a group of current faculty involved in a new interdisciplinary research program in human genetic medicine research encompassing gene therapy, genetic epidemiology and computational biology. The purpose of the proposed facility is to conduct interdisciplinary biomedical research that is of urgent national importance and that would 4employ emerging and novel technologies to directly benefit the fields of cancer and AIDS research, pediatric heritable disease and the human genome project. The expanded PHS-supported biomedical research programs that will occupy the renovated space will broaden the scope of research ad and of research training at USC by (a) promoting interdisciplinary research including research on the emerging technologies of genetic epidemiology and computational biology including research related to pediatric investigation and (b) promoting gene therapy research. Because we have a critical mass of investigators, a history of excellence, an established and deep commitment to molecular and genetic approaches to health problems, a belief in interdisciplinary research, and a rich array of resources, we believe the time if right to expand the Institute for Genetic Medicine activities in Souther California. Such an expansion of the Institute would maximize efficiency, would spark new research and would create opportunities for new research involvement from other members of our research communities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SECOND GENERATION DNA SEQUENCE MANAGEMENT TOOLS Principal Investigator & Institution: Smith, Todd M.; Geospiza, Inc. 3939 Leary Way, Nw Seattle, Wa 98107 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 29-FEB-2004 Summary: (provided by applicant): The human genome project spurred the development of high throughput technologies, especially in the area of DNA sequencing. Not only has this effort produced a draft of the human genome, it's catalyzed development of an entire industry based on DNA sequencing and genomics. Since these technologies produce enormous amounts of data they depend on bioinformatics programs for data management. Phrap, Cross_Match, RepeatMasker and Consed are four programs that played an integral role in the human genome project and became accepted as standard. However, as the technology for sequencing has evolved, so too, have the applications. These new applications include sequencing additional genomes, EST cluster analysis, and genotyping and they have highlighted the need to update standard bioinformatics programs to meet the current needs of a broader community. In this project we will re-engineer Phrap, Cross_Match and Repeat Masker to improve performance by optimizing these algorithms and developing a hierarchical data file to store and manipulate assembled sequence data. Phrap and Cross_Match will also be modified to use XML-formatted data allowing users to apply constraints to sequence assembly. Lastly, we will develop a new program to review, edit, and manipulate sequences, thus giving users unprecedented control over their data. PROPOSED COMMERCIAL APPLICATION: Phrap is widely used in industry and academia for applications involving DNA sequences. There are over 100 commercial sites that would benefit from new versions of Phrap that support incremental assemblies and utilize computer resources better. An API for Phrap will encourage application development creating additional commercialization possibilities for algorithm and application developers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Human Genome Project

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Project Title: SERUM PROTEOMIC BIOMARKER DISCOVERY IN LUNG CANCER Principal Investigator & Institution: Gillette, Michael A.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The applicant describes a five year program leading to independent translational research related to pulmonary and critical care medicine. Although trained as a neuroscientist, the investigator is motivated by clinical experience to propose a career dedicated to the development of molecular diagnostic and targeted therapeutic approaches to medicine, in particular to lung cancer and critical illness. Practical skills in functional genomics, proteomics, molecular biology, biostatistics, and machine learning will be fostered in the laboratory of Dr. Todd Golub, himself an accomplished clinical scientist with a vital independent research program. Director of Cancer Genomics at the Whitehead Institute Center for Genome Research, Dr. Golub is a pioneer and internationally recognized leader in the application of genomics approaches to cancer biology, especially classification and prognosis. This immersion will be complemented by formal instruction in genomics and computational biology, and reinforced by active advising from a team of domain experts. The proposed research plan starts from the tenet that delayed or inaccurate diagnoses can be lethal. Most lung cancer patients present with advanced disease, when the prognosis is grave; many of the critically ill can be given no better than phenomenological descriptions of their disease. The Human Genome Project and other developments in biology and technology have advanced unbiased, whole-genome discovery efforts for improved markers of disease. The principal investigator will undertake such an effort, by 1) creating datasets by mass spectrometry from serum samples of lung cancer patients and controls; 2) defining signatures of disease using machine learning approaches; and 3) identifying proteins and peptides comprising the diagnostic signatures. While the investigator hopes to develop functional lung cancer biomarkers, the methodologies are intended to be applicable throughout medicine. The combined resources of the Massachusetts General Hospital, the Dana Farber Cancer Institute, and the Whitehead Institute will be available to the applicant. These rich environments will promote the success of the serum biomarker discovery project, and the larger cultivation of the investigator towards a goal of independence and productivity in academic medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SNPS IN LUNG CANCER RISK AND THERAPEUTIC RESPONSE Principal Investigator & Institution: Petersdorf, Effie W.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Lung cancer is the greatest single cause of cancer mortality worldwide. Although environmental risk factors have been well defined, smoking prevalence has not declined. Available screening tests for early detection of lung cancer have not lowered overall morbidity and mortality from lung cancer. With the completion of the prototype sequence by the Human Genome Project, information on single nucleotide polymorphisms (SNPs) encoded in cytokine genes has become available. In particular, cytokine gene polymorphisms (CGPs) have recently been shown to be promising predictive markers in several solid tumor model systems and in stem cell transplantation. In the lung cancer model, we hypothesize that CGPs interact with inflammatory stimuli, including tobacco or asbestos exposure, to promote progression to lung cancer. If CGPs modulate risk of lung cancer, then screening tools can be

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developed to assess cancer risk and to detect high-risk patients. If CGPs correlate with outcome of lung cancer therapy, then the use of CGPs to predict response to therapy and guide clinical interventions may be feasible. These hypotheses are eminently testable in large clinical populations of cancer patients and controls for whom extensive clinical and phenotype data is available. To this end, we propose to collaborate with the CARET trial repository (NIH grant CA63673) to access blood samples from lung cancer patients and cancer-free individuals. Our application is an R21 exploratory project in response to PA-01-015 in which we will develop PCR arrays and retrospectively characterize 1,212 study individuals for a panel of 20 CGPs (Specific Aim 1). We will determine whether certain SNPs correlate with the presence of lung cancer (Specific Aim 2), and whether certain SNPs are associated with survival among lung cancer patients (Specific Aim 3). The information will be highly relevant to the design of larger confirmatory clinical studies in the future. Furthermore, the array methodology can be directly and immediately translated to high-throughput population-based testing. If CGPs can be identified as predictive risk markers or prognostic markers in lung cancer, then screening methods can be developed to screen for high-risk individuals before the development of lung cancer; furthermore, if SNPs correlate with clinical response, then use of SNPs genotyping to guide therapeutic interventions can be incorporated into the management care plan of the patient. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE HUMAN GENOME PROJECT AND HEARING LOSS Principal Investigator & Institution: Sorkin, Donna L.; Vice President; Ag Bell Assn for Deaf & Hard of Hearing Assn for Deaf and Hard of Hearing Washington, Dc 20007 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2002 Summary: (provided by applicant): This proposal seeks funding for a stand- alone conference for approximately 600 people on "The Human Genome Project and Hearing Loss" to be convened July 27-28, 2001 in Bethesda, Maryland. The conference would be similar in approach to AG Bell's first scientific symposium at the association's biennial convention in July 2000, which was conducted with NIH support. Last year's symposium, "Biotechnology and the Cochlea," was organized to appeal to an audience of consumers and professionals with an interest in the science of hearing but not necessarily a scientific background. The symposium was an enormous success, drawing nearly 1400 participants including parents, professionals who work hearing-impaired children, and adults with hearing loss. The convention reviews indicated that this was, by far, the most popular session at the AG Bell Convention. The two presentations on genetics at the Symposium were particularly well received with speakers literally inundated with questions, both during and after the symposium. In addition to spurring interest in ongoing science research among the community of non-scientists, the symposium had the wonderful result of encouraging participating scientists to become involved in AG Bell. One speaker, Dr. Heidi Relim of Harvard Medical School, has since authored an article on Connexin 26 testing which will be published in the November/December 2000 issue of Volta Voices, AG Bell's popular magazine. Other collaborations have also developed. This proposal for a research symposium would provide a unique opportunity for this interested group of consumers and professionals to learn about the most recent genetics research. Dr. Francis Collins, Director of the Human Genome Institute, has committed to open the conference on Friday evening, July 27. Dr. James Battey, Director of NIDCD, will provide an overview of NIH-related research as one of the speakers on Saturday morning, July 28, and five other speakers will address specific topics in the area of genetics such as identifying genes and

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Human Genome Project

mechanisms for syndromic and nonsyndromic hearing loss, genetic testing, and genebased therapies for hair cell regeneration. Following the Saturday morning presentations, we will assign speakers to smaller rooms in the hotel to allow one-on-one exchange with the conference participants. Products will include a brochure announcing the symposium for dissemination beyond AG Bell's members (the conference will be heavily publicized in Volta Voices), a proceedings document with summaries of each speakers' remarks, and captioned videos. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE KNOWLEDGEBASE

UNIPROT

PROTEIN

SEQUENCE

AND

FUNCTION

Principal Investigator & Institution: Apweiler, Rolf; European Bioinformatics Institute Wellcome Trust Genome Campus Cambridge, Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant) Bioinformatics infrastructural activities are crucial to modern biological research. Complete and up-to-date databases of biological knowledge are vital for the increasingly information-dependent biological and biotechnological research. With the recent accumulation of genome sequences for many organisms, most notably the draft human sequence, attention is now turning to the identification and function of proteins encoded by these genomes. With the increasing volume and variety of protein sequences and functional information, a central database of protein sequence and function will provide a cornerstone for a wide range of scientists active in modern biological research, and here especially in the field of proteomics. Currently, several databases exist with different coverage of protein sequences and with various types of information annotated. A central resource is necessary to ensure that scientists receive rich and non-redundant information at a single location, and this is what the UniProt project wants to achieve by joining the forces of the SWISS-PROT, TrEMBL and PIR protein database activities The broad, long-term objective of the United Protein Databases (UniProt) can be summarized as the creation, maintenance and provision of a stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces. The work will be built upon solid foundations laid by the three UniProt consortium members, SWlSSPROT and TrEMBL at the European Bioinformatics Institute (EBI) and the Swiss Institute of Bioinformatics (SIB), and the Protein Information Resource (PIR) at Georgetown University Medical Center. UniProt will facilitate development of preventive and curative strategies for health maintenance by allowing researchers to integrate the enormous amount of data from the Human Genome Project and from structural and functional genomics and proteomics projects to understand the genetic and biological mechanisms causing human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WORKSHOP ON NONHUMAN PRIMATE GENOMICS Principal Investigator & Institution: Morton, William R.; Director; National Primate Research Ctr; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 22-JAN-2001; Project End 21-JAN-2002 Summary: This grant application seeks to create a " Workshop on Non-human Primate Genomics", to be held January 22-23, 2001 in Seattle Washington. This workshop will bring together representatives from each of the eight regional Primate Research Centers, as well as prominent experts in the genome based technologies, to address the impact of

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the human Genome Project and associated technologies on non-human primate research. The goal of this workshop is to assess the current state of primate genetics and to make recommendation to the National Center for Research Resources (NCRR) as to the resources that should be put in place to best enable genome related non-human primate research. The workshop will be scheduled over a two-day period. Presentations from representatives of the eight RPRC's as well as the experts in the field of genetics will precede grope discussions and breakout sessions to summarize findings and formulate recommendations. The recent joint announcement by Celera and the federally funded Human Genome Project that the human genome sequence is nearly complete ushers in a new era for primate biology. Since this represents the first time that a primate genome has been sequenced to near completion, it is important that the Regional Primate Centers reflect on this accomplishment and assess what opportunities the human sequence provides for those doing research with non-human primates. In addition to the near completion of the human genome sequence, the past 10 years have witnessed the development of a number of genome based technologies, including DNA arrays, rapid genotyping methods, and proteomics, which have fundamentally changed the nature of human biomedical research. How these technologies can be used to develop resources to better enable non-human primate research needs to be addressed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “human genome project” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for human genome project in the PubMed Central database: •

How is the Human Genome Project Doing, and What Have we Learned so Far? by Guyer MS, Collins FS.; 1995 Nov 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40527

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The Human Genome Project. by Olson MV.; 1993 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46506

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The Human Genome Project: ethical and social implications. by Murray TH, Livny E.; 1995 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=225990

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Translating the genetic library: the goals, methods, and applications of the Human Genome Project. by Keleher C.; 1993 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=225788

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with human genome project, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “human genome project” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for human genome project (hyperlinks lead to article summaries): •

A “quality-first” credo for the Human Genome Project. Author(s): Olson M, Green P. Source: Genome Research. 1998 May; 8(5): 414-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9582184&dopt=Abstract

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A highly complex organization of the regulatory region of the human CYP19 (aromatase) gene revealed by the Human Genome Project. Author(s): Sebastian S, Bulun SE. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 October; 86(10): 4600-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600509&dopt=Abstract

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A history of the Human Genome Project. Author(s): Roberts L, Davenport RJ, Pennisi E, Marshall E. Source: Science. 2001 February 16; 291(5507): 1195. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11233436&dopt=Abstract

6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A new dimension for the human genome project: towards comprehensive expression maps. Author(s): Strachan T, Abitbol M, Davidson D, Beckmann JS. Source: Nature Genetics. 1997 June; 16(2): 126-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9171823&dopt=Abstract

•

A new five-year plan for the U.S. Human Genome Project. Author(s): Collins F, Galas D. Source: Science. 1993 October 1; 262(5130): 43-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8211127&dopt=Abstract

•

A second Human Genome Project? Author(s): Long R. Source: Nature Biotechnology. 1998 September; 16(9): 793. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743089&dopt=Abstract

•

ABCs of molecular cardiology and the impact of the Human Genome Project on clinical cardiology. Author(s): Singh R, Pislaru SV, Simari RD. Source: Cardiology in Review. 2002 January-February; 10(1): 24-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790266&dopt=Abstract

•

Advances in the Human Genome Project. A review. Author(s): Kelavkar U, Shah K. Source: Molecular Biology Reports. 1998 January; 25(1): 27-43. Review. Erratum In: Mol Biol Rep 1999 August; 26(3): 215. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9540065&dopt=Abstract

•

An evaluation of the Ethical, Legal and Social Implications program of the U.S. Human Genome Project. Author(s): Jin J. Source: Princet J Bioeth. 2000 Spring; 3(1): 35-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936136&dopt=Abstract

•

An independent perspective on the Human Genome Project. Author(s): Koonin SE. Source: Science. 1998 January 2; 279(5347): 36-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9441408&dopt=Abstract

42

Human Genome Project

•

An overview of the Human Genome Project and its implications for women. Author(s): Mahowald MB. Source: Women's Health Issues : Official Publication of the Jacobs Institute of Women's Health. 1997 July-August; 7(4): 206-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9283271&dopt=Abstract

•

And the monster is--us? Ethical, legal, and social issues of the Human Genome Project. Author(s): Raskin S. Source: Md Med. 2000 Autumn; 1(4): 23-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11147453&dopt=Abstract

•

Aristotle and the human genome project. Author(s): Wildner M. Source: Lancet. 2000 October 14; 356(9238): 1360. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11073058&dopt=Abstract

•

ASHG human genome committee report. The human genome project: implications for human genetics. Author(s): Caskey CT, Worton RG. Source: American Journal of Human Genetics. 1991 September; 49(3): 687-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1882846&dopt=Abstract

•

Assessing mapping progress in the Human Genome Project. Author(s): Cox DR, Green ED, Lander ES, Cohen D, Myers RM. Source: Science. 1994 September 30; 265(5181): 2031-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8091223&dopt=Abstract

•

Assessing the quality of the DNA sequence from the Human Genome Project. Author(s): Felsenfeld A, Peterson J, Schloss J, Guyer M. Source: Genome Research. 1999 January; 9(1): 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9927479&dopt=Abstract

•

Asthma and the human genome project: summary of the 45th Annual Thomas L. Petty Aspen Lung Conference. Author(s): Drazen JM. Source: Chest. 2003 March; 123(3 Suppl): 447S-9S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629033&dopt=Abstract

Studies

43

•

Bench-to-bedside review: fulfilling promises of the Human Genome Project. Author(s): Chiche JD, Cariou A, Mira JP. Source: Critical Care (London, England). 2002 June; 6(3): 212-5. Epub 2002 March 20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133180&dopt=Abstract

•

Call for a worldwide survey of human genetic diversity: a vanishing opportunity for the Human Genome Project. Author(s): Cavalli-Sforza LL, Wilson AC, Cantor CR, Cook-Deegan RM, King MC. Source: Genomics. 1991 October; 11(2): 490-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1769670&dopt=Abstract

•

Can the human genome project be saved from its critics. and itself? Author(s): Leder P. Source: Cell. 1990 October 5; 63(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2208273&dopt=Abstract

•

cDNA analyses in the human genome project. Author(s): Matsubara K, Okubo K. Source: Gene. 1993 December 15; 135(1-2): 265-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8276268&dopt=Abstract

•

Co-chairman's remarks: Jim Watson: the double helix, messenger RNA and the Human Genome Project--a personal view. Author(s): Gros F. Source: Gene. 1993 December 15; 135(1-2): 305-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8276273&dopt=Abstract

•

Co-chairman's remarks: the human genome project and cancer. Author(s): Dulbecco R. Source: Gene. 1993 December 15; 135(1-2): 259-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8276266&dopt=Abstract

•

Commercial implications of the Human Genome Project. Author(s): Evans GA. Source: Trends in Biotechnology. 1996 May; 14(5): 143-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8645445&dopt=Abstract

44

Human Genome Project

•

Commercial molecular diagnostics in the U.S.: The Human Genome Project to the clinical laboratory. Author(s): Amos J, Patnaik M. Source: Human Mutation. 2002 April; 19(4): 324-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11933187&dopt=Abstract

•

Comparative genomics: the key to understanding the Human Genome Project. Author(s): Clark MS. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. 1999 February; 21(2): 121-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10193186&dopt=Abstract

•

Complementary DNA sequencing: expressed sequence tags and human genome project. Author(s): Adams MD, Kelley JM, Gocayne JD, Dubnick M, Polymeropoulos MH, Xiao H, Merril CR, Wu A, Olde B, Moreno RF, et al. Source: Science. 1991 June 21; 252(5013): 1651-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2047873&dopt=Abstract

•

Cracking the code: how will the Human Genome Project affect life as we know it? Author(s): Chew M. Source: The Medical Journal of Australia. 2000 December 4-18; 173(11-12): 590. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11379497&dopt=Abstract

•

Data disclosure in the human genome project. Author(s): Dunham I. Source: Molecular Medicine Today. 1998 August; 4(8): 335-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9755451&dopt=Abstract

•

Dental implications of the Human Genome Project. Author(s): Hamilton J. Source: J Calif Dent Assoc. 2001 January; 29(1): 35-47. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11323870&dopt=Abstract

•

Discussing HUGO: the German debate on the ethical implications of the Human Genome Project. Author(s): Boshammer S, Kayss M, Runtenberg C, Ach JS. Source: The Journal of Medicine and Philosophy. 1998 June; 23(3): 324-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9736194&dopt=Abstract

Studies

45

•

Divining and altering the future: implications from the Human Genome Project. Author(s): Lin JH. Source: Jama : the Journal of the American Medical Association. 1998 November 4; 280(17): 1532. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9809737&dopt=Abstract

•

DoE still involved in the Human Genome Project. Department of Energy. Author(s): Decker JF. Source: Nature. 2000 March 16; 404(6775): 222. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10749187&dopt=Abstract

•

Drug discovery of the future: the implications of the human genome project. Author(s): Reiss T. Source: Trends in Biotechnology. 2001 December; 19(12): 496-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11711192&dopt=Abstract

•

Effect of the human genome project on the practice of adolescent medicine. Author(s): Toriello HV. Source: Adolescent Medicine (Philadelphia, Pa.). 2002 June; 13(2): 201-12, V. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986031&dopt=Abstract

•

Ethical issues raised by the Human Genome Project. Author(s): Smith JE. Source: Am J Hosp Pharm. 1993 September; 50(9): 1945-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8135246&dopt=Abstract

•

Ethical, legal and social issues surrounding the human genome project. Author(s): Mowat D. Source: Internal Medicine Journal. 2002 March; 32(3): 89-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885849&dopt=Abstract

•

Ethics and the human genome project. Author(s): Paske GH. Source: Kans Med. 1995 Summer; 96(2): 58, 57. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7500596&dopt=Abstract

•

Ethics and the Human Genome Project. Author(s): Durfy SJ. Source: Archives of Pathology & Laboratory Medicine. 1993 May; 117(5): 466-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8489332&dopt=Abstract

46

Human Genome Project

•

Ethics, technology, and the human genome project. Author(s): Brody H. Source: J Clin Ethics. 1991 Winter; 2(4): 278-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1804398&dopt=Abstract

•

Eugenics and the Human Genome Project. Author(s): Hubbard R. Source: Genewatch. 2000 July; 13(3): 7-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814102&dopt=Abstract

•

Family physicians' perspectives on genetics and the human genome project. Author(s): Fetters MD, Doukas DJ, Phan KL. Source: Clinical Genetics. 1999 July; 56(1): 28-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466414&dopt=Abstract

•

First moves of the USSR Human Genome Project. Author(s): Bayev AA. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1991 January; 5(1): 70-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1991588&dopt=Abstract

•

Five stages of the Human Genome Project. Author(s): Strohman RC. Source: Nature Biotechnology. 1999 February; 17(2): 112. Erratum In: Nat Biotechnol 1999 April; 17(4): 314. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10052331&dopt=Abstract

•

From Mendel to the Human Genome Project: the implications for nurse education. Author(s): Burton H, Stewart A. Source: Nurse Education Today. 2003 July; 23(5): 380-5; Discussion 386-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831804&dopt=Abstract

•

Fruits of human genome project and private venture, and their impact on life science. Author(s): Ikekawa A, Ikekawa S. Source: Yakugaku Zasshi. Journal of the Pharmaceutical Society of Japan. 2001 December; 121(12): 845-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766401&dopt=Abstract

•

Gaps in the Human Genome Project. Author(s): Roach JC, Siegel AF, van den Engh G, Trask B, Hood L. Source: Nature. 1999 October 28; 401(6756): 843-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10553897&dopt=Abstract

Studies

47

•

Genetic landmarks through philately: the Human Genome Project and the new millennium. Author(s): Galenzoski K, Chudley A. Source: Clinical Genetics. 2001 June; 59(6): 393-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11453970&dopt=Abstract

•

Geneticists discuss ethics of human genome project. Author(s): Bosch X. Source: Lancet. 1998 October 31; 352(9138): 1448. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9808003&dopt=Abstract

•

Geneticizing disability: the Human Genome Project and the commodification of self. Author(s): Fitzgerald J. Source: Issues in Law & Medicine. 1998 Fall; 14(2): 147-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9807243&dopt=Abstract

•

Genetics and ethics. Is the ministry prepared to answer ethical questions raised by the Human Genome Project? Author(s): O'Rourke KD. Source: Health Progress (Saint Louis, Mo.). 2001 March-April; 82(2): 28-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299877&dopt=Abstract

•

Genetics and ethics. Issues and implications of the Human Genome Project. Author(s): Hamel R. Source: Health Progress (Saint Louis, Mo.). 2001 March-April; 82(2): 22-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299875&dopt=Abstract

•

Genetics infuses new life into human physiology: implications of the human genome project for anesthesiology and perioperative medicine. Author(s): Schwinn DA, Booth JV. Source: Anesthesiology. 2002 February; 96(2): 261-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818753&dopt=Abstract

•

Genomic medicine: the sorcerer's new broom? The limitations of the human genome project. Author(s): Coulter I. Source: The Western Journal of Medicine. 2001 December; 175(6): 424-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11733442&dopt=Abstract

48

Human Genome Project

•

Genotoxicology and risk assessment in the era of the human genome project. Author(s): Vorce RL, Stemmer PM. Source: Journal of Toxicology. Clinical Toxicology. 1996; 34(5): 521-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8800191&dopt=Abstract

•

Genotype-phenotype correlations with personality traits of healthcare professionals: a new use for the Human Genome Project. Author(s): Philpot CR. Source: The Medical Journal of Australia. 2002 June 17; 176(12): 620. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437013&dopt=Abstract

•

Genotype-phenotype correlations with personality traits of healthcare professionals: a new use for the Human Genome Project. Author(s): Brown L. Source: The Medical Journal of Australia. 2002 June 17; 176(12): 620; Author Reply 620. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064966&dopt=Abstract

•

Genotype-phenotype correlations with personality traits of healthcare professionals: a new use for the Human Genome Project. Author(s): Fitzgerald DA, Isaacs D. Source: The Medical Journal of Australia. 2002 April 1; 176(7): 339-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12013329&dopt=Abstract

•

High performance computing for the human genome project. Author(s): Bohm K. Source: Computer Methods and Programs in Biomedicine. 1995 February; 46(2): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7796579&dopt=Abstract

•

Homosexuality and the human genome project: private and public choices. Author(s): Gabard DL. Source: Journal of Homosexuality. 1999; 37(1): 25-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10203068&dopt=Abstract

•

How analytical chemists saved the human genome project.or at least gave it a helping hand. Author(s): Zubritsky E. Source: Analytical Chemistry. 2002 January 1; 74(1): 23A-26A. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795801&dopt=Abstract

Studies

49

•

How human geneticists in US view commercialization of the Human Genome Project. Author(s): Rabino I. Source: Nature Genetics. 2001 September; 29(1): 15-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528382&dopt=Abstract

•

How is the Human Genome Project doing, and what have we learned so far? Author(s): Guyer MS, Collins FS. Source: Proceedings of the National Academy of Sciences of the United States of America. 1995 November 21; 92(24): 10841-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7479895&dopt=Abstract

•

How much use is the Human Genome Project? Author(s): Hadden S. Source: Nature. 2000 April 6; 404(6778): 541-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10766213&dopt=Abstract

•

How will the human genome project change cardiovascular medicine? Author(s): Komajda M, Charron P. Source: Heart (British Cardiac Society). 2001 August; 86(2): 123-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454817&dopt=Abstract

•

How will the Human Genome Project improve our quality of life? Author(s): Cantor CR. Source: Nature Biotechnology. 1998 March; 16(3): 212-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9527989&dopt=Abstract

•

Human genome diversity: what about the other human genome project? Author(s): Greely HT. Source: Nature Reviews. Genetics. 2001 March; 2(3): 222-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256074&dopt=Abstract

•

Human Genome Project aims to finish 'working draft' next year. Author(s): Wadman M. Source: Nature. 1999 March 18; 398(6724): 177. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10094029&dopt=Abstract

•

Human Genome Project and cancer: the ethical implications for clinical practice. Author(s): Bassford TL, Hauck L. Source: Semin Oncol Nurs. 1993 August; 9(3): 134-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8210778&dopt=Abstract

50

Human Genome Project

•

Human Genome Project and cystic fibrosis--a symbiotic relationship. Author(s): Tolstoi LG, Smith CL. Source: Journal of the American Dietetic Association. 1999 November; 99(11): 1421-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10570680&dopt=Abstract

•

Human genome project and mutation research: a mating that needs to happen. Author(s): Carrano AV. Source: Environmental and Molecular Mutagenesis. 1994; 23 Suppl 24: 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8162907&dopt=Abstract

•

Human Genome Project and pharmacogenomics--implications for pharmacy. Author(s): Carrico JM. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 2000 January-February; 40(1): 115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10665260&dopt=Abstract

•

Human genome project Europe. Author(s): Williamson AR, Dykes CW, Romanos M, Bailey D. Source: Trends in Pharmacological Sciences. 1997 September; 18(9): 303-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9345844&dopt=Abstract

•

Human genome project to complete ahead of schedule. Author(s): Berger A. Source: Bmj (Clinical Research Ed.). 1998 September 26; 317(7162): 834. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9786691&dopt=Abstract

•

Human genome project. Author(s): Roberts PJ. Source: Ann Chir Gynaecol. 2001; 90(1): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336366&dopt=Abstract

•

Human genome project. Author(s): Shapiro LJ. Source: The Western Journal of Medicine. 1993 February; 158(2): 181. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8434472&dopt=Abstract

•

Human Genome Project. Author(s): Sawicki MP, Samara G, Hurwitz M, Passaro E Jr. Source: American Journal of Surgery. 1993 February; 165(2): 258-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8427408&dopt=Abstract

Studies

51

•

Human Genome Project. Author(s): O'Connor NK. Source: The Journal of Family Practice. 1993 January; 36(1): 14-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8419496&dopt=Abstract

•

Human genome project. Author(s): Ross DW. Source: Archives of Pathology & Laboratory Medicine. 1990 October; 114(10): 1084. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2222152&dopt=Abstract

•

Human genome project. Author(s): Johnson VP. Source: S D J Med. 1992 June; 45(6): 161-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1502543&dopt=Abstract

•

Human Genome Project. Author(s): Durfy SJ. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 1991 September-October; 82(5): 357. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1768999&dopt=Abstract

•

Human Genome Project. And the gene number is.? Author(s): Pennisi E. Source: Science. 2000 May 19; 288(5469): 1146-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10841722&dopt=Abstract

•

Human Genome Project. Chromosome 21 done, phase two begun. Author(s): Pennisi E. Source: Science. 2000 May 12; 288(5468): 939. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10841703&dopt=Abstract

•

Human genome project. Commercial firms win U.S. sequencing funds. Author(s): Marshall E. Source: Science. 1999 July 16; 285(5426): 310. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10438288&dopt=Abstract

•

Human genome project. Emphasis turns from mapping to large-scale sequencing. Author(s): Marshall E. Source: Science. 1995 June 2; 268(5215): 1270-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7761844&dopt=Abstract

52

Human Genome Project

•

Human genome project. Genome institute wrestles mightily with its future. Author(s): Pennisi E. Source: Science. 2002 November 29; 298(5599): 1694-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459558&dopt=Abstract

•

Human genome project. New office for HUGO in Soviet Union. Author(s): Aldhous P. Source: Nature. 1991 June 27; 351(6329): 683. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2062358&dopt=Abstract

•

Human Genome Project. Sequencers endorse plan for a draft in 1 year. Author(s): Marshall E. Source: Science. 1999 May 28; 284(5419): 1439, 1441. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10383314&dopt=Abstract

•

Human genome project. Sequencers split over data release. Author(s): Kahn P. Source: Science. 1996 March 29; 271(5257): 1798-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8596944&dopt=Abstract

•

Human genome project. Still room for HUGO? Author(s): Anderson C, Aldhous P. Source: Nature. 1992 January 2; 355(6355): 4-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1731199&dopt=Abstract

•

Human genome project. The honeymoon is over. Author(s): Anderson GC. Source: Nature. 1990 July 26; 346(6282): 309. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2374602&dopt=Abstract

•

Human genome project. Tit for tat on patents? Author(s): Aldhous P. Source: Nature. 1991 October 31; 353(6347): 785. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1944543&dopt=Abstract

•

Human genome project. Variation is now the theme. Author(s): Goodfellow PN. Source: Nature. 1992 October 29; 359(6398): 777-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1359422&dopt=Abstract

Studies

53

•

Human Genome Project: data quality. Author(s): Green P. Source: Science. 1998 February 20; 279(5354): 1115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9508680&dopt=Abstract

•

Human genome project: implications for medical science. Author(s): Karunanayake EH. Source: Ceylon Med J. 1999 December; 44(4): 151-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895263&dopt=Abstract

•

Human genome project: Italian contribution. Future directions. Author(s): Dulbecco R. Source: Journal of Cellular Physiology. 1997 November; 173(2): 140-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9365512&dopt=Abstract

•

Human Genome Project: Mapping the way ahead. Author(s): Little P. Source: Nature. 1992 October 1; 359(6394): 367-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1406946&dopt=Abstract

•

Human genome project: past, present, future. Author(s): Weissenbach J. Source: Ernst Schering Res Found Workshop. 2002; (36): 1-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859560&dopt=Abstract

•

Human genome project: pharmacogenomics and drug development. Author(s): Ganguly NK, Bano R, Seth SD. Source: Indian J Exp Biol. 2001 October; 39(10): 955-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883519&dopt=Abstract

•

Human genome project: who will pay? Author(s): Siekevitz P. Source: Science. 1989 December 8; 246(4935): 1236. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2588001&dopt=Abstract

•

Human leucocyte differentiation antigens and the human genome project. Author(s): Zola H. Source: J Biol Regul Homeost Agents. 2001 October-December; 15(4): 384-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11860229&dopt=Abstract

54

Human Genome Project

•

Impact of Human Genome Project on biological sciences. Author(s): Arundhati. Source: Indian J Physiol Pharmacol. 2000 April; 44(2): 121-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10846624&dopt=Abstract

•

Impact of human genome project on medical practice. Author(s): Joshi VR. Source: J Assoc Physicians India. 2002 June; 50: 856; Author Reply 856-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12240869&dopt=Abstract

•

Impact of human genome project on medical practice. Author(s): Sridhar GR. Source: J Assoc Physicians India. 2001 October; 49: 995-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11848333&dopt=Abstract

•

Impact of Human Genome Project on medical practice. Author(s): Lele RD. Source: J Assoc Physicians India. 2001 October; 49: 959-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11848325&dopt=Abstract

•

Impact of the Human Genome Project on epidemiologic research. Author(s): Ellsworth DL, Hallman DM, Boerwinkle E. Source: Epidemiologic Reviews. 1997; 19(1): 3-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9360897&dopt=Abstract

•

Impact of the human genome project on medical practice. Author(s): Rossiter BJ, Caskey CT. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 1995 January; 2(1): 14-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7834449&dopt=Abstract

•

Impact of the human genome project on pediatric endocrinology. Author(s): Polychronakos C. Source: Hormone Research. 2003; 59(2): 55-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589108&dopt=Abstract

•

Impact of the Human Genome Project on the clinical management of sporadic cancers. Author(s): Fey MF. Source: The Lancet Oncology. 2002 June; 3(6): 349-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107022&dopt=Abstract

Studies

55

•

Impact of the human genome project on the principles for classification and nomenclature of 5-HT receptors. Author(s): Hoyer D, Humphrey PA, Barnard EA. Source: Annals of the New York Academy of Sciences. 1998 December 15; 861: 230-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9928260&dopt=Abstract

•

Implication of human genome project for pediatric practice. Author(s): Verma IC. Source: Indian Pediatrics. 2003 July; 40(7): 607-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881615&dopt=Abstract

•

Implications for nursing of the Human Genome Project. Author(s): Munro CL. Source: Neonatal Netw. 1999 April; 18(3): 7-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10418432&dopt=Abstract

•

Implications of the human genome project for clinical neurosurgery. Author(s): Cantor CR. Source: Clin Neurosurg. 1991; 37: 173-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2009686&dopt=Abstract

•

Implications of the Human Genome Project for obstetrics and gynecology. Author(s): Schimpf MO, Domino SE. Source: Obstetrical & Gynecological Survey. 2001 July; 56(7): 437-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435952&dopt=Abstract

•

Implications of the human genome project for the identification of genetic risk of coronary heart disease and its prevention in children. Author(s): Cullen P, Funke H. Source: Nutr Metab Cardiovasc Dis. 2001 October; 11 Suppl 5: 45-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063776&dopt=Abstract

•

Implications of the human genome project for understanding gene-environment interactions. Author(s): Velazquez A, Bourges H. Source: Nutrition Reviews. 1999 May; 57(5 Pt 2): S39-41; Discussion S41-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10391024&dopt=Abstract

•

Information metaphors and the human genome project. Author(s): Fogle T. Source: Perspectives in Biology and Medicine. 1995 Summer; 38(4): 535-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7659486&dopt=Abstract

56

Human Genome Project

•

Interest in the human genome project reaches new heights. Author(s): Palca J. Source: Nature. 1987 February 19-25; 325(6106): 651. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3821856&dopt=Abstract

•

International protection of genetic information: the progression of the Human Genome Project and the current framework of human rights doctrines. Author(s): Tauer JE. Source: Denver J Int Law Policy. 2001 Summer-Fall; 29(3-4): 209-37. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769121&dopt=Abstract

•

Introducing 'cancer genetics report' as a new section in JJCO: dawn of postsequencing age of human genome project. Author(s): Yoshida T. Source: Japanese Journal of Clinical Oncology. 1999 October; 29(10): 457-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10645797&dopt=Abstract

•

Introduction to the post-Human Genome Project era, a target for interactions between polygenic and/or multiphenotypical components in cancer control in South America. Author(s): Iscovich J. Source: Cadernos De Saude Publica / Ministerio Da Saude, Fundacao Oswaldo Cruz, Escola Nacional De Saude Publica. 1998; 14 Suppl 3: 15-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9819461&dopt=Abstract

•

James Watson to head NIH human genome project. Author(s): Palca J. Source: Nature. 1988 September 15; 335(6187): 193. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3045567&dopt=Abstract

•

Japan's human genome project takes shape. Author(s): Swinbanks D. Source: Nature. 1991 June 20; 351(6328): 593. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2052075&dopt=Abstract

•

Joe Doupe Young Investigators Award. The Human Genome Project: tools for the identification of disease genes. Author(s): Hudson TJ. Source: Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. 1998 December; 21(6): 267-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9885761&dopt=Abstract

Studies

57

•

LIMS and the Human Genome Project. Author(s): Hunkapiller T, Hood L. Source: Biotechnology (N Y). 1991 December; 9(12): 1344-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1367767&dopt=Abstract

•

Major events in the U.S. Human Genome Project and related projects. Author(s): U.S. Department of Energy Office of Science, Office of Biological and Environmental Research. Source: Md Med. 2000 Autumn; 1(4): 16-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11147452&dopt=Abstract

•

Managing all those bytes: the Human Genome Project. Author(s): Cuticchia AJ, Chipperfield MA, Porter CJ, Kearns W, Pearson PL. Source: Science. 1993 October 1; 262(5130): 47-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8211128&dopt=Abstract

•

Mapmakers--progress in the human genome project. Author(s): Spurr NK. Source: Biochemical Society Transactions. 1996 February; 24(1): 285-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8674688&dopt=Abstract

•

Medical and ethical consequences of the human genome project. Author(s): Collins FS. Source: J Clin Ethics. 1991 Winter; 2(4): 260-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1804396&dopt=Abstract

•

Medical genetics and the Human Genome Project: a historical review. Author(s): Haq MM. Source: Tex Med. 1993 March; 89(3): 68-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8451744&dopt=Abstract

•

Medical genetics, the human genome project and public health. Author(s): Bobrow M, Grimbaldeston AH. Source: Journal of Epidemiology and Community Health. 2000 September; 54(9): 645-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942439&dopt=Abstract

•

Micro-anatomo politics: mapping the Human Genome Project. Author(s): Flower MJ, Heath D. Source: Culture, Medicine and Psychiatry. 1993 March; 17(1): 27-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8354070&dopt=Abstract

58

Human Genome Project

•

Milestone or genomania? The relevance of the Human Genome Project to biological aging and the age-related diseases. Author(s): Blumenthal HT. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2001 September; 56(9): M529-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11524444&dopt=Abstract

•

Milestones in the Human Genome Project: genesis to postgenome. Author(s): Trent RJ. Source: The Medical Journal of Australia. 2000 December 4-18; 173(11-12): 591-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11379498&dopt=Abstract

•

Molecular medicine: a primer for clinicians. Part XIII: The human genome project and the practice of medicine. Author(s): Lindahl R. Source: S D J Med. 2001 October; 54(10): 405-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668890&dopt=Abstract

•

National Academy looks at human genome project, sees progress. Author(s): Lewin R. Source: Science. 1987 February 13; 235(4790): 747-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3468626&dopt=Abstract

•

Network-based informatics support of research collaborations in the Human Genome Project and the Human Brain Project. Author(s): Miller PL, Nadkarni PM, Kucherlapati R, Krauter KS, Kidd KK, Ward DC, Shepherd GM, Berkowicz D. Source: Medinfo. 1995; 8 Pt 2: 1541-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8591495&dopt=Abstract

•

New goals for the U.S. Human Genome Project: 1998-2003. Author(s): Collins FS, Patrinos A, Jordan E, Chakravarti A, Gesteland R, Walters L. Source: Science. 1998 October 23; 282(5389): 682-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9784121&dopt=Abstract

•

NHLBI genomics initiatives : looking beyond the human genome project. Author(s): Lenfant C. Source: Circulation. 2000 February 8; 101(5): 468-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10662740&dopt=Abstract

Studies

59

•

Nuts and bolts of psychiatric genetics: building on the Human Genome Project. Author(s): Evans KL, Muir WJ, Blackwood DH, Porteous DJ. Source: Trends in Genetics : Tig. 2001 January; 17(1): 35-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11163920&dopt=Abstract

•

Opportunities for population-based studies of complex genetic disorders after the human genome project. Author(s): Vaessen N, van Duijn CM. Source: Epidemiology (Cambridge, Mass.). 2001 May; 12(3): 360-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11337607&dopt=Abstract

•

Orchestrating the Human Genome Project. Author(s): Cantor CR. Source: Science. 1990 April 6; 248(4951): 49-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2181666&dopt=Abstract

•

Overview of the human genome project in Japan. Author(s): Sakaki Y. Source: Jpn J Hum Genet. 1996 June; 41(2): 239-42. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8771988&dopt=Abstract

•

Patenting cDNA 1993: efforts and happenings (Human Genome Project; NIH: US PTO; onco-mouse; European Patents). Author(s): Zinder ND. Source: Gene. 1993 December 15; 135(1-2): 295-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8276271&dopt=Abstract

•

Patenting genes. J. Craig Venter and the Human Genome Project. Author(s): Rowe PM. Source: Molecular Medicine Today. 1995 April; 1(1): 12-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415131&dopt=Abstract

•

Patents and the human genome project--new claims for old? Author(s): Gilbert PX, Walter C. Source: Trends in Biotechnology. 2001 February; 19(2): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164553&dopt=Abstract

•

Pharmacogenetic applications of the Human Genome project. Author(s): Liggett SB. Source: Nature Medicine. 2001 March; 7(3): 281-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231618&dopt=Abstract

60

Human Genome Project

•

Policy implications of the Human Genome Project for women. Author(s): Cassel CK. Source: Women's Health Issues : Official Publication of the Jacobs Institute of Women's Health. 1997 July-August; 7(4): 225-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9283275&dopt=Abstract

•

Presient's page: the human genome project: implications for cardiologists and their patients. Author(s): Beller GA. Source: Journal of the American College of Cardiology. 2000 July; 36(1): 295-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10898450&dopt=Abstract

•

Primary care and the human genome project. Into the breach. Author(s): Doukas DJ. Source: Archives of Family Medicine. 1993 November; 2(11): 1179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8124493&dopt=Abstract

•

Private venture galvanizes public effort on Human Genome Project. Author(s): Stephenson J. Source: Jama : the Journal of the American Medical Association. 1998 June 24; 279(24): 1933, 1935. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9643842&dopt=Abstract

•

Promotion of the human genome project. Author(s): Billings PR. Source: Science. 1990 November 23; 250(4984): 1071. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2251496&dopt=Abstract

•

Reflections on mental retardation and eugenics, old and new: Mensa and the Human Genome Project. Author(s): Smith JD. Source: Mental Retardation. 1994 June; 32(3): 234-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8084276&dopt=Abstract

•

Relevance of the Human Genome Project to inherited metabolic disease. Author(s): Burn J. Source: Journal of Inherited Metabolic Disease. 1994; 17(4): 421-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7967492&dopt=Abstract

Studies

61

•

Religious leaders' attitudes and beliefs about genetics research and the Human Genome Project. Author(s): Phan KL, Doukas DJ, Fetters MD. Source: J Clin Ethics. 1995 Fall; 6(3): 237-46. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8605386&dopt=Abstract

•

Richard Wooster on cancer and the Human Genome Project (interview by Ezzie Hutchinson). Author(s): Wooster R. Source: The Lancet Oncology. 2001 March; 2(3): 176-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902570&dopt=Abstract

•

Robotics and the human genome project. New robotic-based systems automate the replication of cloned DNA libraries. Author(s): Uber DC. Source: Biotechnology (N Y). 1994 January; 12(1): 80-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7764330&dopt=Abstract

•

Scientific commentary: the scientific foundations and medical and social prospects of the Human Genome Project. Author(s): Lander ES. Source: The Journal of Law, Medicine & Ethics : a Journal of the American Society of Law, Medicine & Ethics. 1998 Fall; 26(3): 184-8, 178. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11066875&dopt=Abstract

•

Scientists unveil the next step in the human genome project. Author(s): Gottlieb S. Source: Bmj (Clinical Research Ed.). 2002 November 9; 325(7372): 1056. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428602&dopt=Abstract

•

Screening workers for genetic hypersusceptibility: potential ethical, legal, and social implications from the Human Genome Project. Author(s): Wicks AC, Sever LE, Harty R, Gajewski SW, Marcus-Smith M. Source: Journal of Health and Human Services Administration. 1999 Summer; 22(1): 11632. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10848187&dopt=Abstract

•

Searching for the Holy Grail: the Human Genome Project and its implications. Author(s): Morse A. Source: J Law Health. 1998-99; 13(2): 219-56. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10947395&dopt=Abstract

62

Human Genome Project

•

Segmental duplications: organization and impact within the current human genome project assembly. Author(s): Bailey JA, Yavor AM, Massa HF, Trask BJ, Eichler EE. Source: Genome Research. 2001 June; 11(6): 1005-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11381028&dopt=Abstract

•

Shattuck lecture--medical and societal consequences of the Human Genome Project. Author(s): Collins FS. Source: The New England Journal of Medicine. 1999 July 1; 341(1): 28-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10387940&dopt=Abstract

•

Sickle cell screening policies as portent: how will the human genome project affect public sector genetic services? Author(s): Phoenix DD, Lybrook SM, Trottier RW, Hodgin FC, Crandall LA. Source: Journal of the National Medical Association. 1995 November; 87(11): 807-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8907815&dopt=Abstract

•

Social and medical consequences of the Human Genome Project. 20-21 February 1999, Landesmuseum fur Technik und Arbeit, Mannheim, Germany. Author(s): Keilbart M. Source: Functional & Integrative Genomics. 2000 September; 1(2): 140-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11793229&dopt=Abstract

•

Social attitudes and the Human Genome Project: ethical implications. Author(s): Rodriguez E. Source: Linacre Q. 2000 February; 67(1): 28-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199283&dopt=Abstract

•

Societal and medical consequences of the Human Genome Project. Inter-disciplinary approaches to human genetics. Author(s): Keilbart M. Source: Functional & Integrative Genomics. 2000 September; 1(2): 146-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11793231&dopt=Abstract

•

Solving the insurance/genetic fair/unfair discrimination dilemma in light of the Human Genome Project. Author(s): Holmes EM. Source: Ky Law J. 1996; 85(3): 503-664. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11863023&dopt=Abstract

Studies

63

•

Some ethical implications of the Human Genome Project. Author(s): Epstein CJ. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 2000 May-June; 2(3): 193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256665&dopt=Abstract

•

Some thoughts on the Human Genome Project. Author(s): Danks DM. Source: The Medical Journal of Australia. 1990 May 7; 152(9): 488-9. Erratum In: Med J Aust 1990 June 18; 152(12): 676. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2381341&dopt=Abstract

•

Structural genomics: beyond the human genome project. Author(s): Burley SK, Almo SC, Bonanno JB, Capel M, Chance MR, Gaasterland T, Lin D, Sali A, Studier FW, Swaminathan S. Source: Nature Genetics. 1999 October; 23(2): 151-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10508510&dopt=Abstract

•

Summary: The Human Genome Project, an agenda for science and society. Author(s): Richardson WC. Source: Bull N Y Acad Med. 1992 January-February; 68(1): 162-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1555022&dopt=Abstract

•

Susceptibility genes and neurological disorders: learning the right lessons from the human genome project. Author(s): Grodin MA, Laurie GT. Source: Archives of Neurology. 2000 November; 57(11): 1569-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11074788&dopt=Abstract

•

Teaching about the human genome project. Author(s): Baumiller RC. Source: American Journal of Human Genetics. 1991 August; 49(2): 501-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1867211&dopt=Abstract

•

The “Asilomar process” and the Human Genome Project. Author(s): Kaback MM. Source: Perspectives in Biology and Medicine. 2001 Spring; 44(2): 230-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370157&dopt=Abstract

64

Human Genome Project

•

The clinical impact of the Human Genome Project: inherited variants in cancer care. Author(s): Hopkinson I, Mackay J. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002; 13 Suppl 4: 105-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401674&dopt=Abstract

•

The double helix revisited. The man who launched the Human Genome Project celebrates its success. Author(s): Watson J. Source: Time. 2000 July 3; 156(1): 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11009719&dopt=Abstract

•

The ethical implications of the Human Genome Project for the workplace. Author(s): Brady T. Source: Int J Appl Philos. 1995 Summer; 10(1): 47-56. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902192&dopt=Abstract

•

The Human Genome Project (HGP). Author(s): Peakall D, Shugart L. Source: Ecotoxicology (London, England). 2002 February; 11(1): 7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895016&dopt=Abstract

•

The Human Genome Project after a decade: policy issues. Author(s): Burris J, Cook-Deegan R, Alberts B. Source: Nature Genetics. 1998 December; 20(4): 333-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9843203&dopt=Abstract

•

The human genome project aims for 2003. Author(s): Goodman L. Source: Genome Research. 1998 October; 8(10): 997-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9799787&dopt=Abstract

•

The Human Genome Project and bioethics. Author(s): Juengst ET. Source: Kennedy Institute of Ethics Journal. 1991 March; 1(1): 71-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10113820&dopt=Abstract

•

The Human Genome Project and breast cancer. Author(s): Olopade OI. Source: Women's Health Issues : Official Publication of the Jacobs Institute of Women's Health. 1997 July-August; 7(4): 209-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9283272&dopt=Abstract

Studies

65

•

The human genome project and clinical medicine. Author(s): Rossiter BJ, Caskey CT. Source: Oncology (Huntingt). 1992 November; 6(11): 61-8, 71; Discussion 71, 75-6. Review. Erratum In: Oncology (Huntingt) 1993 January; 7(1): 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1445778&dopt=Abstract

•

The Human Genome Project and clinical medicine. Author(s): McKusick VA. Source: Hosp Pract (Off Ed). 1991 October 15; 26(10): 15-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1918193&dopt=Abstract

•

The Human Genome Project and clinical medicine: adenomatous polyposis coli and the Marfan syndrome as examples. Author(s): McKusick VA. Source: Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1993 July-August; 34(4): 2436. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8213153&dopt=Abstract

•

The Human Genome Project and eugenic concerns. Author(s): Garver KL, Garver B. Source: American Journal of Human Genetics. 1994 January; 54(1): 148-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8279465&dopt=Abstract

•

The Human Genome Project and eugenics: identifying the impact on individuals with mental retardation. Author(s): Kuna J. Source: Mental Retardation. 2001 April; 39(2): 158-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340967&dopt=Abstract

•

The Human Genome Project and eye disease: clinical implications. Author(s): Wiggs JL. Source: Archives of Ophthalmology. 2001 November; 119(11): 1710-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709025&dopt=Abstract

•

The Human Genome Project and gene therapy: a genetic counselor's perspective. Author(s): Rice E. Source: The Journal of Perinatal & Neonatal Nursing. 1998 December; 12(3): 16-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326430&dopt=Abstract

66

Human Genome Project

•

The Human Genome Project and genome variation. Author(s): Cotton RG. Source: Internal Medicine Journal. 2002 July; 32(7): 285-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088344&dopt=Abstract

•

The Human Genome Project and health behavior and health education research. Author(s): Sorenson JR, Cheuvront B. Source: Health Education Research. 1993 December; 8(4): 589-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10146565&dopt=Abstract

•

The Human Genome Project and health care's high-tech future. Author(s): Coile RC Jr. Source: Russ Coile's Health Trends. 2000 November; 13(1): 1, 4-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11155657&dopt=Abstract

•

The human genome project and international health. Author(s): Watson JD, Cook-Deegan RM. Source: Jama : the Journal of the American Medical Association. 1990 June 27; 263(24): 3322-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2348545&dopt=Abstract

•

The human genome project and its impact on psychiatry. Author(s): Cowan WM, Kopnisky KL, Hyman SE. Source: Annual Review of Neuroscience. 2002; 25: 1-50. Epub 2002 January 22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052903&dopt=Abstract

•

The human genome project and its implications. Author(s): Mahajan VS, Chauhan SS. Source: Trop Gastroenterol. 2001 October-December; 22(4): 177-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11963320&dopt=Abstract

•

The human genome project and medical genetics. Author(s): Harper PS. Source: Journal of Medical Genetics. 1992 January; 29(1): 1-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1552535&dopt=Abstract

•

The human genome project and molecular anthropology. Author(s): Stoneking M. Source: Genome Research. 1997 February; 7(2): 87-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9049626&dopt=Abstract

Studies

67

•

The Human Genome Project and public perception: truth and consequences. Author(s): Pelias MZ, Markward NJ. Source: Emory Law J. 2000 Summer; 49(3): 837-58. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645564&dopt=Abstract

•

The Human Genome Project and the courts: gene therapy and beyond. Author(s): Mehlman MJ. Source: Judicature. 1999 November-December; 83(3): 124-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737163&dopt=Abstract

•

The Human Genome Project and the future of diagnostics, treatment and prevention. Author(s): van Ommen GJ. Source: Journal of Inherited Metabolic Disease. 2002 May; 25(3): 183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137226&dopt=Abstract

•

The human genome project and the future of diagnostics, treatment, and prevention. Author(s): van Ommen GJ, Bakker E, den Dunnen JT. Source: Lancet. 1999 July; 354 Suppl 1: Si5-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437848&dopt=Abstract

•

The human genome project and the future of medicine. Author(s): Collins FS. Source: Annals of the New York Academy of Sciences. 1999 June 30; 882: 42-55; Discussion 56-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10415885&dopt=Abstract

•

The Human Genome Project and the future of medicine. Author(s): Guyer MS, Collins FS. Source: Am J Dis Child. 1993 November; 147(11): 1145-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8237907&dopt=Abstract

•

The Human Genome Project and the role of genetics in health care. Author(s): van Ommen GJ. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 1998 August; 36(8): 515-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9806451&dopt=Abstract

•

The Human Genome Project and the social contract: a law policy approach. Author(s): Byk C. Source: The Journal of Medicine and Philosophy. 1992 August; 17(4): 371-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1431656&dopt=Abstract

68

Human Genome Project

•

The Human Genome Project and women. Author(s): Mahowald MB. Source: Women's Health Issues : Official Publication of the Jacobs Institute of Women's Health. 1997 July-August; 7(4): 204-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9283270&dopt=Abstract

•

The human genome project as social policy: implications for clinical medicine. Author(s): Annas GJ. Source: Bull N Y Acad Med. 1992 January-February; 68(1): 126-34. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1555019&dopt=Abstract

•

The Human Genome Project in the dock. Author(s): Kirby M. Source: The Medical Journal of Australia. 2000 December 4-18; 173(11-12): 599-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11379501&dopt=Abstract

•

The human genome project is complete. How do we develop a handle for the pump? Author(s): Little J, Khoury MJ, Bradley L, Clyne M, Gwinn M, Lin B, Lindegren ML, Yoon P. Source: American Journal of Epidemiology. 2003 April 15; 157(8): 667-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697570&dopt=Abstract

•

The Human Genome Project promises insights into aging. Author(s): Gordon J. Source: Geriatrics. 1989 November; 44(11): 89-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2806921&dopt=Abstract

•

The Human Genome Project relevant to genetics education in high school. Author(s): McInerney JD. Source: American Journal of Human Genetics. 1993 January; 52(1): 235-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8434600&dopt=Abstract

•

The Human Genome Project reveals a continuous transfer of large mitochondrial fragments to the nucleus. Author(s): Mourier T, Hansen AJ, Willerslev E, Arctander P. Source: Molecular Biology and Evolution. 2001 September; 18(9): 1833-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11504863&dopt=Abstract

Studies

69

•

The Human Genome Project. Author(s): Klug A. Source: Iubmb Life. 2001 January; 51(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419689&dopt=Abstract

•

The Human Genome Project. Author(s): Sinha S, Chattopadhyay P. Source: Natl Med J India. 2000 July-August; 13(4): 169-73. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11002681&dopt=Abstract

•

The Human Genome Project. Author(s): Lanchbury JS. Source: British Journal of Rheumatology. 1998 February; 37(2): 119-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9569063&dopt=Abstract

•

The human genome project. Author(s): Bodmer WF. Source: Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion. 1994 April; Suppl: 3-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7886305&dopt=Abstract

•

The human genome project. Author(s): Rossiter BJ, Caskey CT. Source: Clinical Obstetrics and Gynecology. 1993 September; 36(3): 466-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8104748&dopt=Abstract

•

The human genome project. Author(s): Olson MV. Source: Proceedings of the National Academy of Sciences of the United States of America. 1993 May 15; 90(10): 4338-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8506271&dopt=Abstract

•

The Human Genome Project. Author(s): Crawford MH. Source: Human Biology; an International Record of Research. 1990 August; 62(4): Iii-Iv. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2210712&dopt=Abstract

•

The Human Genome Project. Author(s): Sillence D. Source: The Medical Journal of Australia. 1990 May 7; 152(9): 486-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2381340&dopt=Abstract

70

Human Genome Project

•

The human genome project. Author(s): Fabrizio T. Source: Nord Med. 1990; 105(1): 16-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2300435&dopt=Abstract

•

The human genome project. Author(s): Aschheim E. Source: Jama : the Journal of the American Medical Association. 1992 February 5; 267(5): 653. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1731125&dopt=Abstract

•

The human genome project. Author(s): Rosenberg LE. Source: Bull N Y Acad Med. 1992 January-February; 68(1): 113-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1555017&dopt=Abstract

•

The human genome project. Author(s): Fontelo PA. Source: Archives of Pathology & Laboratory Medicine. 1991 May; 115(5): 426-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2021307&dopt=Abstract

•

The Human Genome Project. Author(s): Peters KF, Hadley DW. Source: Cancer Nursing. 1997 February; 20(1): 62-71, Quiz 72-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9033151&dopt=Abstract

•

The Human Genome Project. History, goals, and progress to date. Author(s): Engel LW. Source: Archives of Pathology & Laboratory Medicine. 1993 May; 117(5): 459-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8489331&dopt=Abstract

•

The human genome project. Prospects and implications for clinical medicine. Author(s): Green ED, Waterston RH. Source: Jama : the Journal of the American Medical Association. 1991 October 9; 266(14): 1966-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1895475&dopt=Abstract

Studies

71

•

The human genome project. Purpose and potential. Author(s): Caskey CT, Rossiter BJ. Source: The Journal of Pharmacy and Pharmacology. 1992 February; 44 Suppl 1: 198-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1348284&dopt=Abstract

•

The Human Genome Project. Recent genetic advances will have far-reaching implications for Catholic health care. Author(s): Reilly PR. Source: Health Progress (Saint Louis, Mo.). 2001 March-April; 82(2): 24-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299876&dopt=Abstract

•

The Human Genome Project. Revealing the shared inheritance of all humankind. Author(s): Collins FS, Mansoura MK. Source: Cancer. 2001 January 1; 91(1 Suppl): 221-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11148583&dopt=Abstract

•

The human genome project: a DOE perspective. Author(s): Barnhart BJ. Source: Basic Life Sci. 1988; 46: 161-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3223870&dopt=Abstract

•

The human genome project: a dream becoming a reality. Author(s): Haddad FF, Yeatman TJ, Shivers SC, Reintgen DS. Source: Surgery. 1999 June; 125(6): 575-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372021&dopt=Abstract

•

The human genome project: a false dawn?. Interview by Judy Jones. Author(s): Zimmern RL. Source: Bmj (Clinical Research Ed.). 1999 November 13; 319(7220): 1282. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10559036&dopt=Abstract

•

The Human Genome Project: a generation's psyche and a society's revolution. Author(s): Cooper DL. Source: Molecular Diagnosis : a Journal Devoted to the Understanding of Human Disease Through the Clinical Application of Molecular Biology. 2000 June; 5(2): 87-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11066009&dopt=Abstract

•

The human genome project: a historical perspective. Author(s): Mundy C. Source: Pharmacogenomics. 2001 February; 2(1): 37-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11258196&dopt=Abstract

72

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•

The Human Genome Project: a paradigm for information management in the life sciences. Author(s): Pearson ML, Soll D. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1991 January; 5(1): 35-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1991581&dopt=Abstract

•

The Human Genome Project: a player's perspective. Author(s): Olson MV. Source: Journal of Molecular Biology. 2002 June 14; 319(4): 931-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079320&dopt=Abstract

•

The Human Genome Project: a public good. Author(s): Hudson K. Source: Health Matrix (Cleveland, Ohio : 1991). 2002 Summer; 12(2): 367-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430360&dopt=Abstract

•

The Human Genome Project: an update. Author(s): Peters KF, Menaker TJ, Wilson PL, Hadley DW. Source: Cancer Nursing. 2001 August; 24(4): 287-92; Quiz 292-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502037&dopt=Abstract

•

The Human Genome Project: answers closer than you think? Author(s): Forsdyke DR. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1990 November; 4(14): 3261. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2227217&dopt=Abstract

•

The Human Genome Project: applications in the diagnosis and treatment of neurologic disease. Author(s): Evans GA. Source: Archives of Neurology. 1998 October; 55(10): 1287-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9779654&dopt=Abstract

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The Human Genome Project: creating an infrastructure for biology and medicine. Author(s): Yager TD, Nickerson DA, Hood LE. Source: Trends in Biochemical Sciences. 1991 December; 16(12): 454, 456, 458 Passim. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1781022&dopt=Abstract

Studies

73

•

The Human Genome Project: ethical and legal considerations for neuroscience nurses. Author(s): Tazbir J. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 2001 August; 33(4): 180-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497069&dopt=Abstract

•

The Human Genome Project: ethical and social implications. Author(s): Murray TH, Livny E. Source: Bulletin of the Medical Library Association. 1995 January; 83(1): 14-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7703933&dopt=Abstract

•

The human genome project: exploring its progress and successes and the ethical, legal, and social implications. Author(s): Zneimer SM. Source: Clin Leadersh Manag Rev. 2002 May-June; 16(3): 151-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046269&dopt=Abstract

•

The Human Genome Project: for better or for worse? Author(s): Dawson K, Singer P. Source: The Medical Journal of Australia. 1990 May 7; 152(9): 484-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2381339&dopt=Abstract

•

The Human Genome Project: from mapping to sequencing. Author(s): Weissenbach J. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 1998 August; 36(8): 511-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9806450&dopt=Abstract

•

The human genome project: has blind reductionism gone too far? Author(s): Tauber AI, Sarkar S. Source: Perspectives in Biology and Medicine. 1992 Winter; 35(2): 220-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1557300&dopt=Abstract

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The Human Genome Project: how do we protect Australians? Author(s): Stott Despoja N. Source: The Medical Journal of Australia. 2000 December 4-18; 173(11-12): 596-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11379500&dopt=Abstract

74

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•

The Human Genome Project: impact on obstetrics and gynecology. Author(s): Elias S. Source: Obstetrical & Gynecological Survey. 1993 July; 48(7): 441-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8355923&dopt=Abstract

•

The Human Genome Project: implications for nursing. Author(s): Lessick M, Williams J. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 1994 February; 3(1): 49-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8124379&dopt=Abstract

•

The human genome project: implications for the endocrinologist. Author(s): Francke U. Source: J Pediatr Endocrinol Metab. 2001; 14 Suppl 6: 1395-408. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837493&dopt=Abstract

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The Human Genome Project: implications for the practicing obstetrician. Author(s): Sachs BP, Korf B. Source: Obstetrics and Gynecology. 1993 March; 81(3): 458-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8437805&dopt=Abstract

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The Human Genome Project: implications for the treatment of musculoskeletal disease. Author(s): Jaffurs D, Evans CH. Source: J Am Acad Orthop Surg. 1998 January-February; 6(1): 1-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9692936&dopt=Abstract

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The Human Genome Project: interaction of the physical sciences with biology. Author(s): Patrinos AA. Source: The Journal of Law, Medicine & Ethics : a Journal of the American Society of Law, Medicine & Ethics. 2000 Winter; 28(4 Suppl): 54-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11244845&dopt=Abstract

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The Human Genome Project: issues and ethics. Author(s): Kopala B. Source: Mcn. the American Journal of Maternal Child Nursing. 1997 January-February; 22(1): 9-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9002683&dopt=Abstract

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The human genome project: its implications in clinical medicine. Author(s): Lele RD. Source: J Assoc Physicians India. 2003 April; 51: 373-80. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723652&dopt=Abstract

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The Human Genome Project: lessons from large-scale biology. Author(s): Collins FS, Morgan M, Patrinos A. Source: Science. 2003 April 11; 300(5617): 286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690187&dopt=Abstract

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The Human Genome Project: misguided science policy. Author(s): Rechsteiner MC. Source: Trends in Biochemical Sciences. 1991 December; 16(12): 455, 457, 459. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1781023&dopt=Abstract

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The Human Genome Project: nursing must get on board. Author(s): Gottlieb LN. Source: The Canadian Journal of Nursing Research = Revue Canadienne De Recherche En Sciences Infirmieres. 1998 Fall; 30(3): 3-6. English, French. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10030181&dopt=Abstract

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The human genome project: past, present, and future. Author(s): Watson JD. Source: Science. 1990 April 6; 248(4951): 44-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2181665&dopt=Abstract

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The Human Genome Project: promise versus reality. Author(s): Ayala FJ. Source: Law Hum Genome Rev. 1998 July-December; (9): 23-34. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10335333&dopt=Abstract

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The human genome project: prospects and politics. Author(s): Silverman PH. Source: Am Biotechnol Lab. 1990 April; 8(5): 4, 6, 8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1366415&dopt=Abstract

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The Human Genome Project: reaching the finish line. Author(s): Waterston R, Sulston JE. Source: Science. 1998 October 2; 282(5386): 53-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9786797&dopt=Abstract

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The Human Genome Project: the central ethical challenge. Author(s): Pellegrino ED. Source: St Thomas Law Rev. 2001 Summer; 13(4): 815-25. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661542&dopt=Abstract

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The Human Genome Project: the next decade. Author(s): Gardiner RM. Source: Archives of Disease in Childhood. 2002 June; 86(6): 389-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023162&dopt=Abstract

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The Human Genome Project: under an international ethical microscope. Author(s): Knoppers BM, Chadwick R. Source: Science. 1994 September 30; 265(5181): 2035-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8091225&dopt=Abstract

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The Human Genome Project: view from the Department of Energy. Author(s): Patrinos A, Drell DW. Source: J Am Med Womens Assoc. 1997 Winter; 52(1): 8-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9033165&dopt=Abstract

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The Human Genome Project: view from the National Institutes of Health. Author(s): Fink L, Collins FS. Source: J Am Med Womens Assoc. 1997 Winter; 52(1): 4-7, 15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9033164&dopt=Abstract

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The human genome project: what impact on basic research? Author(s): Johnson RS. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1987 December; 1(6): 502-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3479371&dopt=Abstract

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The human genome project: what's in it for the pediatric gastroenterologist? Author(s): Walker WA. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 September; 31(3): 218. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997360&dopt=Abstract

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The Human Genome Project--an overview. Author(s): Bentley DR. Source: Medicinal Research Reviews. 2000 May; 20(3): 189-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10797463&dopt=Abstract

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The Human Genome Project--does South Africa have a role to play? Author(s): Jenkins T. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1991 December 7; 80(11-12): 536-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1745935&dopt=Abstract

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The Human Genome Project--promise and problems. Author(s): Kirby M. Source: J Contemp Health Law Policy. 1994 Fall; 11(1): 1-21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10142389&dopt=Abstract

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The human genome project--some implications of extensive “reverse genetic” medicine. Author(s): Friedmann T. Source: American Journal of Human Genetics. 1990 March; 46(3): 407-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2309696&dopt=Abstract

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The human genome project--what will we do with it? Author(s): Steele R. Source: Can Oncol Nurs J. 2000 Summer; 10(3): 91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11894280&dopt=Abstract

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The ideology of the human genome project. Author(s): Tauber AI, Sarkar S. Source: Journal of the Royal Society of Medicine. 1993 September; 86(9): 537-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8410895&dopt=Abstract

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The impact of the Human Genome Project on medical genetics. Author(s): Williams SJ, Hayward NK. Source: Trends in Molecular Medicine. 2001 May; 7(5): 229-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11325635&dopt=Abstract

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The implications of the Human Genome Project for family practice. Author(s): Whittaker LA. Source: The Journal of Family Practice. 1992 September; 35(3): 294-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517727&dopt=Abstract

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The key is in the genes, or is it.? With the human genome project completed, the question is 'what comes next'? Author(s): Moore A. Source: Embo Reports. 2000 August; 1(2): 100-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11265744&dopt=Abstract

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The molecular dissection of human diseases after the human genome project. Author(s): Peltonen L. Source: The Pharmacogenomics Journal. 2001; 1(1): 5-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913727&dopt=Abstract

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The new biology enters the generalist pediatrician's office: lessons from the Human Genome Project. Author(s): McCabe ER. Source: Pediatrics in Review / American Academy of Pediatrics. 1999 September; 20(9): 314-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10473662&dopt=Abstract

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The origin and implications of the Human Genome Project: scientific overview. Author(s): Dietrich WF. Source: Natl Cathol Bioeth Q. 2001 Winter; 1(4): 489-95. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854559&dopt=Abstract

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The power of public access: the human genome project and the scientific process. Author(s): Quackenbush J. Source: Nature Genetics. 2001 September; 29(1): 4-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528377&dopt=Abstract

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The role of the human genome project in disease prevention. Author(s): Gottesman MM, Collins FS. Source: Preventive Medicine. 1994 September; 23(5): 591-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7845920&dopt=Abstract

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The study of neural tube defects after the Human Genome Project and folic acid fortification of foods. Author(s): Graf WD, Oleinik OE. Source: European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery. [et Al] = Zeitschrift Fur Kinderchirurgie. 2000 December; 10 Suppl 1: 9-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214847&dopt=Abstract

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Thoughts on the relationship of the human genome project to neurology. Author(s): Bird TD. Source: Archives of Neurology. 2001 November; 58(11): 1764-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708981&dopt=Abstract

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Translating the genetic library: the goals, methods, and applications of the Human Genome Project. Author(s): Keleher C. Source: Bulletin of the Medical Library Association. 1993 July; 81(3): 274-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8374581&dopt=Abstract

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UNESCO program for the human genome project. Author(s): Grisolia S. Source: Genomics. 1991 February; 9(2): 404-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2004791&dopt=Abstract

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Update on the Human Genome Project. Author(s): Dizikes GJ. Source: Clin Lab Med. 1995 December; 15(4): 973-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8838234&dopt=Abstract

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Usefulness of the Human Genome Project. Author(s): Weis JH. Source: Science. 1990 June 29; 248(4963): 1595. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2363043&dopt=Abstract

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Waiting for the working draft from the human genome project. A huge achievement, but not of immediate medical use. Author(s): Cardon LR, Watkins H. Source: Bmj (Clinical Research Ed.). 2000 May 6; 320(7244): 1223-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10797018&dopt=Abstract

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WebWise: navigating the Human Genome Project. Author(s): Pruitt KD. Source: Genome Research. 1997 November; 7(11): 1038-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9371738&dopt=Abstract

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WebWise: web sites of the Human Genome Project. Author(s): Pruitt KD. Source: Genome Research. 1998 November; 8(11): 1109-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9847075&dopt=Abstract

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What does the human genome project mean for medicine? Author(s): Kennedy MA. Source: N Z Med J. 2001 April 27; 114(1130): 190-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11396670&dopt=Abstract

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What the human genome project will not tell us: the role of micro-organisms in disease. Author(s): Raza A. Source: Leukemia Research. 2001 February; 25(2): 179-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166834&dopt=Abstract

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When the human genome project and state street collide. Author(s): Locke SD, Kalow DA. Source: Nature Biotechnology. 2000 September; 18(9): 1009-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10973226&dopt=Abstract

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Who will lead human genome project? Author(s): Ebbert E. Source: Nature. 1988 May 5; 333(6168): 7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3362209&dopt=Abstract

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Why genetics competency is a must. The Human Genome Project. Author(s): Saver C. Source: Imprint. 1999 April-May; 46(3): 44-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382450&dopt=Abstract

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CHAPTER 2. NUTRITION AND HUMAN GENOME PROJECT Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and human genome project.

Finding Nutrition Studies on Human Genome Project The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “human genome project” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “human genome project” (or a synonym): •

CPGA: a prototype for analysis of the sequence-structure-function relationship on the Human Genome Project. Source: Liebman, M.N. Brugge, A.L. Computers and DNA the proceedings of the Interface between Computation Science and Nucleic Acid Sequencing Workshop, held December 12 to 16, 1988 in Santa Fe, New Mexico / edited by George I Bell, Thomas G Marr. Redwood City, Calif. : Addison-Wesley Pub. Co., 1990. page 183-202. ISBN: 020151561X

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Human Genome Project and cystic fibrosis--a symbiotic relationship. Author(s): Department of Biomedical Engineering, Boston University, Mass., USA. Source: Tolstoi, L G Smith, C L J-Am-Diet-Assoc. 1999 November; 99(11): 1421-7 00028223

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Implications of the human genome project for understanding gene-environment interactions. Author(s): Unidad de Genetica de la Nutricion, Universidad Nacional Autonoma de Mexico, Mexico, D.F. Source: Velazquez, A Bourges, H Nutr-Revolume 1999 May; 57(5 Pt 2): S39-41; discussion S41-2 0029-6643

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The study of neural tube defects after the Human Genome Project and folic acid fortification of foods. Author(s): Department of Pediatrics, University of Washington, School of Medicine, Seattle, USA. [email protected] Source: Graf, W D Oleinik, O E Eur-J-Pediatr-Surg. 2000 December; 10 Suppl 19-12 09397248

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND HUMAN GENOME PROJECT Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to human genome project. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to human genome project and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “human genome project” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to human genome project: •

“Playing God” and germline intervention. Author(s): Peters T. Source: The Journal of Medicine and Philosophy. 1995 August; 20(4): 365-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8568437&dopt=Abstract

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Bio-medical technology: of the kingdom or of the cosmos? Author(s): Breck J. Source: St Vladmirs Theol Q. 1988; 32(1): 5-26. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11659731&dopt=Abstract

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Charting the map of life. Author(s): Schmidt CW.

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Source: Environmental Health Perspectives. 2001 January; 109(1): A24-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11171541&dopt=Abstract •

Chemical dissection and the ethics of preclinical science. Author(s): McPhate G. Source: Vesalius. 1997 June; 3(1): 46-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11619422&dopt=Abstract

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Christians and the Genome Project. Scripture can help us chart a moral path through the new genetic sciences. Author(s): Verhey A. Source: Health Progress (Saint Louis, Mo.). 2002 July-August; 83(4): 12-8, 58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12141077&dopt=Abstract

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Commerce and genetic diagnostics. Author(s): Silverman PH. Source: The Hastings Center Report. 1995 May-June; 25(3 Suppl): S15-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11654185&dopt=Abstract

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Confocal laser scanning microscopy and 3-D reconstructions of neuronal structures in human brain cortex. Author(s): Belichenko PV, Dahlstrom A. Source: Neuroimage. 1995 September; 2(3): 201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9343603&dopt=Abstract

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Decoding the human genome: second thoughts. Author(s): Dossey L. Source: Alternative Therapies in Health and Medicine. 2000 September; 6(5): 10-4, 63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979157&dopt=Abstract

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Draft report to annual and central conferences, Dec 1990: an invitation to explore a frontier. Author(s): United Methodist Church. Genetic Science Task Force. Source: Engage Soc Action. 1991 January; 4(1): 17-27. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11659313&dopt=Abstract

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Environmental genome project: a positive sequence of events. Author(s): Booker SM. Source: Environmental Health Perspectives. 2001 January; 109(1): A22-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11171540&dopt=Abstract

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European Parliament on genetics. Author(s): European Parliament. Source: Bull Med Ethics. 1990 April; No. 57: 8-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11659240&dopt=Abstract

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Examining the past, present, and future of clinical genetics. Author(s): Gordon H. Source: Minn Med. 1992 May; 75(5): 11-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1593991&dopt=Abstract

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Foreword: law, medicine and socially responsible research. Author(s): Holmes-Farley SR, Grodin MA. Source: American Journal of Law & Medicine. 1998; 24(2-3): 153-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9702270&dopt=Abstract

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Frontiers of genetic research: science and religion. Author(s): Friend W. Source: Origins. 1995 January 19; 24(31): 522-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11659914&dopt=Abstract

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Genetic discrimination: perspectives of consumers. Author(s): Lapham EV, Kozma C, Weiss JO. Source: Science. 1996 October 25; 274(5287): 621-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8849455&dopt=Abstract

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Genetics and cardiac anomalies: the heart of the matter. Author(s): Prasad C, Chudley AE. Source: Indian J Pediatr. 2002 April; 69(4): 321-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12019554&dopt=Abstract

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Genetics and ethics. Is the ministry prepared to answer ethical questions raised by the Human Genome Project? Author(s): O'Rourke KD. Source: Health Progress (Saint Louis, Mo.). 2001 March-April; 82(2): 28-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299877&dopt=Abstract

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Genetics and ethics. Issues and implications of the Human Genome Project. Author(s): Hamel R. Source: Health Progress (Saint Louis, Mo.). 2001 March-April; 82(2): 22-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299875&dopt=Abstract

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Jurisprudence and genetics. Law governing the new technologies should be grounded in a moral vision. Author(s): Kaveny MC. Source: Health Progress (Saint Louis, Mo.). 2001 March-April; 82(2): 43-7, 78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299880&dopt=Abstract

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Little People of America: position statement on genetic discoveries in dwarfism (1996). Author(s): Ricker R. Source: Genetic Resour. 1997; 11(1): 29. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12731507&dopt=Abstract

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Medical ethics in the European Community. Author(s): Riis P. Source: Journal of Medical Ethics. 1993 March; 19(1): 7-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8459444&dopt=Abstract

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Medical provision in the twenty-first century. Author(s): Shan Y, Busia K. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 2002 April; 8(2): 193-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006127&dopt=Abstract

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Neurosciences - A neurosurgeon's perspective. Author(s): Abraham J. Source: Neurology India. 1999 March; 47(1): 3-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10339700&dopt=Abstract

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New center a stroke of gene-ius. Author(s): Greene LA. Source: Environmental Health Perspectives. 2001 January; 109(1): A22-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11171539&dopt=Abstract

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Noninvasive gene delivery to the liver by mechanical massage. Author(s): Liu F, Huang L. Source: Hepatology (Baltimore, Md.). 2002 June; 35(6): 1314-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12029616&dopt=Abstract

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On the 50th anniversary of solving the structure of DNA. Author(s): Samson LD.

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Source: Environmental Health Perspectives. 2003 May; 111(6): A329-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790141&dopt=Abstract •

Patenting DNA and amino acid sequences--an Australian perspective. Author(s): Keays D. Source: Health Law J. 1999; 7: 69-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11066370&dopt=Abstract

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Reading maps of the genes: interpreting the spatiality of genetic knowledge. Author(s): Hall E. Source: Health & Place. 2003 June; 9(2): 151-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753798&dopt=Abstract

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Religion and the human genome. Author(s): Cole-Turner R. Source: Journal of Religion and Health. 1992 Summer; 31(2): 161-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11659480&dopt=Abstract

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Religious leaders' attitudes and beliefs about genetics research and the Human Genome Project. Author(s): Phan KL, Doukas DJ, Fetters MD. Source: J Clin Ethics. 1995 Fall; 6(3): 237-46. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8605386&dopt=Abstract

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Tailored genes: IVF, genetic engineering, and eugenics. Author(s): Ewing CM. Source: Reprod Genet Eng. 1988; 1(1): 31-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11650379&dopt=Abstract

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Technology. Part II: New opportunities for health care? Author(s): Reeder L. Source: Integr Healthc Rep. 1999 November; : 1-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10915296&dopt=Abstract

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The challenge of genetics. Author(s): Place MD. Source: Health Progress (Saint Louis, Mo.). 2001 March-April; 82(2): 6-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299883&dopt=Abstract

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The dignity and vocation of the human person. A Christian bioethical vision. Author(s): George F.

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Source: Health Progress (Saint Louis, Mo.). 2001 March-April; 82(2): 60-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299884&dopt=Abstract •

The fullness of life. Integrating patient care, teaching, and research. Author(s): Sulmasy DP. Source: Health Progress (Saint Louis, Mo.). 1993 January-February; 74(1): 76-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10123577&dopt=Abstract

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The gene politics of the European Community. Author(s): Goerlich A, Krannich M. Source: Reprod Genet Eng. 1989; 2(3): 201-18. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11652004&dopt=Abstract

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The Human Genome Project. Recent genetic advances will have far-reaching implications for Catholic health care. Author(s): Reilly PR. Source: Health Progress (Saint Louis, Mo.). 2001 March-April; 82(2): 24-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299876&dopt=Abstract

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The way it is, is not the way it will be. Author(s): Flower J. Source: Health Forum Journal. 1999 July-August; 42(4): 16-22, 24, 26-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10539015&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON HUMAN GENOME PROJECT Overview In this chapter, we will give you a bibliography on recent dissertations relating to human genome project. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “human genome project” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on human genome project, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Human Genome Project ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to human genome project. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

A Map of Life: an Epistemological Study of the Human Genome Project by Leal, Belita (Maria Isabel), PhD from Rice University, 1999, 360 pages http://wwwlib.umi.com/dissertations/fullcit/9928552

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Canadian Newspaper Coverage of the Human Genome Project by Ayed, Nahlah; Ma from The University of Manitoba (Canada), 2002, 131 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76888

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The Ethics of Genetic Technology: Knowledge, the Common Good, and Healing. the Case of the Human Genome Project by Vicini, Andrea; PhD from Boston College, 2000, 399 pages http://wwwlib.umi.com/dissertations/fullcit/9995940

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The Impact of Teacher Participation in a Workshop on Genetics: Effect on Teacher Preparedness and Confidence and Student Achievement (human Genome Project) by Ayers-Knetter, Rebecca Lynn, PhD from University of Kansas, 1995, 164 pages http://wwwlib.umi.com/dissertations/fullcit/9609562

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The Political Economy of Large-scale Science: the Emergence of the Human Genome Project by Loeppky, Rodney David; PhD from York University (Canada), 2002, 327 pages http://wwwlib.umi.com/dissertations/fullcit/NQ75197

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The Politics of Feeling Good: Splicing the Human Genome Project and Nuclear Power by Marcus, Lawrence Douglas, PhD from Washington University, 1994, 352 pages http://wwwlib.umi.com/dissertations/fullcit/9523282

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. PATENTS ON HUMAN GENOME PROJECT Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “human genome project” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on human genome project, we have not necessarily excluded non-medical patents in this bibliography.

Patent Applications on Human Genome Project As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to human genome project:

8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm. 9 This has been a common practice outside the United States prior to December 2000.

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DNA pooling methods for quantitative traits using unrelated populations or sib pairs Inventor(s): Bader, Joel S.; (Stamford, CT), Bansal, Aruna; (Branford, CT), Sham, Pak; (London, GB) Correspondence: Mintz, Levin, Cohn, Ferris,; Glovsky And Popeo, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20030044821 Date filed: April 22, 2002 Abstract: Identifying the genetic determinants for disease and disease predisposition remains one of the outstanding goals of the human genome project. When large patient populations are available, genetic approaches using single nucleotide polymorphism markers have the potential to identify relevant genes directly. While individual genotyping is the most powerful method for establishing association, determining allele frequencies in DNA pooled on the basis of phenotypic value can also reveal association at a much-reduced cost. Here we analyze pooling methods to establish association between a genetic polymorphism and a quantitative phenotype. Exact results are provided for the statistical power for a number of pooling designs where the phenotype is described by a variance components model and the fraction of the population pooled is optimized to minimize the population requirements. For low to moderate sibling phenotypic correlation, unrelated populations are more powerful than sib pair populations with an equal number of individuals; for sibling phenotypic correlations above 75%, however, designs selecting the sib pairs with the greatest phenotype difference become more powerful. For sibling phenotype correlations below 75%, pooling extreme unrelated individuals is the most powerful design for sib pair populations. The optimal pooling fractions for each design are constant over a wide range of parameters. These results for quantitative phenotypes differ from those reported for qualitative phenotypes, for which unrelated populations are more powerful than sib pairs and concordant designs are more powerful than discordant, and have immediate relevance to ongoing association studies and anticipated whole-genome scans. Excerpt(s): This application claims priority to U.S. Ser. No. 09/932,480, filed Aug. 17, 2001; U.S. Ser. No. 60/226,465 filed Aug. 18, 2000 [Cura 396], and to U.S. Ser. No. 60/230,580 filed Sep. 5, 2000 [Cura 396A], both of which are incorporated herein by reference in their entireties. The complex diseases that present the greatest challenge to modem medicine, including cancer, cardiovascular disease, and metabolic disorders, arise through the interplay of numerous genetic and environmental factors. One of the primary goals of the human genome project is to assist in the risk-assessment, prevention, detection, and treatment of these complex disorders by identifying the genetic components. Disentangling the genetic and environmental factors requires carefully designed studies. One approach is to study highly homogenous populations (Nillson and Rose 1999; Rabinow, 1999; Frank 2000). A recognized drawback of this approach, however, is that disease-associated markers or causative alleles found in an isolated population might not be relevant for a larger population. An attractive alternative is to use well-matched case-control studies of a more diverse population. A second alternative is to study siblings, inherently matched for environmental effects. Even with a well-matched sample set, the genetic factors contributing to an aberrant phenotype may be difficult to determine. Traditional linkage analysis methods identify physical regions of DNA whose inheritance pattern correlates with the inheritance of a particular trait (Liu 1997; Sham 1997, Ott 1999). These regions may contain millions of nucleotides and tens to hundreds of genes, and identifying the causative mutation or a

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tightly linked marker is still a challenge. A more recent approach is to use a sufficiently dense marker set to identify causative changes directly. Single nucleotide polymorphisms, or SNPs, can provide such a marker set (Cargill et al. 1999). These are typically bi-allelic markers with linkage disequilibrium extending an estimated 10,000 to 100,000 nucleotides in heterogeneous human populations (Kruglyak 1999; Collins et al. 2000). Tens to hundreds of thousands of these closely spaced markers are required for a complete scan of the 3 billion nucleotides in the human genome. Because each SNP constitutes a separate test, the significance threshold must be adjusted for multiple hypotheses (p-value.about.10.sup.-8) to identify statistically meaningful associations. Consequently, hundreds to thousands of individuals are required for association studies (Risch and Merikangas 1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

NOVEL METHOD FOR THE PRESELECTION OF SHOTGUN CLONES OF THE GENOME OR A PORTION THEREOF OF AN ORGANISM Inventor(s): CAHILL, DOLORES; (BERLIN, DE), FRANCIS, FIONA; (PARIS, FR), HENNIG, STEFFEN; (BERLIN, DE), LEHRACH, HANS; (BERLIN, DE), POUSTKA, ANNEMARIE; (HEIDELBERG, DE), RADELOF, UWE; (KLEINMACHNOW, DE), SERANSKI, PETER; (HEIDELBERG, DE), STEINFATH, MATTHIAS; (BERLIN, DE) Correspondence: Fish & Richardson, PC; 4350 LA Jolla Village Drive; Suite 500; San Diego; CA; 92122; US Patent Application Number: 20020012911 Date filed: March 26, 1999 Excerpt(s): This specification cites a number of published references. All these references are Incorporated herein by reference. The present invention relates to a method for the preselection of shotgun clones, e.g., cosmids, PACs, BACs, etc. of a genome of an organism, or of parts of the genome of an organism that significantly reduces the time and workload associated with the further processing of shotgun clones, for example, In sequencing projects such as the human genome project. The invention relies on a combination of steps including the transfer of shotgun clones to a carrier, e.g., nylon membrane, glass chip, etc. where the clones bind, preferably hybridize to a set of specifically selected probes, e.g., DNA oligonucleotides, PNA oligonucleotides or pools of DNA or/and PNA oligonucleotides, further antibodies, fragments or derivatives thereof which are labeled or unlabeled. Each probe of said set interacts to 1 to 99% (ideally 50%) of all shotgun clones (nucleic acid fragments) in all investigated shotgun libraries. Clones that are characterized as being divergent as a result of the binding experiment in all likelihood represent different parts of the genome or of the investigated part of the genome. The preselection for such divergent clones will reduce the number of redundant analysis of, e.g., DNA sequences. Since the foundation of the Human Genome Organisation (HUGO) in McKsuick V. A., Genomics 5(2) (1989), 385 less then 5 percent of the human genome has been sequenced (Beck S., http:l/www.ebl.ac.uk/-sterklgen- ome-MOT/ (1998)). Completion of the project until 2005 will therefore require either appropriate increases in funding or the use of new methods (3,4). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with human genome project, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “human genome project” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on human genome project. You can also use this procedure to view pending patent applications concerning human genome project. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON HUMAN GENOME PROJECT Overview This chapter provides bibliographic book references relating to human genome project. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on human genome project include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “human genome project” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on human genome project: •

Cleft Lip and Palate: From Origin to Treatment Source: New York, NY: Oxford University Press, Inc. 2002. 536 p. Contact: Available from Oxford University Press. Customer Service Department, 2001 Evans Road, Cary, NC 27513. (800) 445-9714. Fax (919) 677-1303. E-mail: [email protected]. Website: www.oup-usa.org. PRICE: $125.00 plus shipping and handling. ISBN: 0195139062. Summary: Cleft lip with or without cleft palate and isolated cleft palate, collectively termed oral clefts, are the second most common birth defects among newborns. This textbook on cleft lip and palate covers a broach range of theoretical, experimental, and clinical topics and is written by experts in the fields of craniofacial development, biomedical sciences, genetics, epidemiology, and public health. The text includes 42 chapters in six sections: basic embryology, clinical features, epidemiology, genetics,

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treatment, and public health issues. Specific topics include the orofacial examination, classification, syndromes with orofacial clefting, epidemiology, birth defects surveillance systems, international perspective on oral clefts, maternal nutrition, environmental risk factors, the Human Genome Project, twin studies, patient care team, infant feeding, stage of cleft lip and palate reconstruction, evaluation and management of speech and language disorders, pediatric dental care, the role of the orthodontist, genetic counseling, psychological care of children with cleft lip and palate in the family, international surgical missions, prevention of oral clefts (folic acid and multivitamin supplements), personal and societal implications of oral clefts, insurance and coverage of care, ethical issues, and translating research findings into public health action. Each chapter concludes with a list of references and the text concludes with a directory of Internet resources, a glossary of terms, and a subject index.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “human genome project” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “human genome project” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “human genome project” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A very human adventure : the story and implications of the Human Genome Project by Tom Levi; ISBN: 1897636008; http://www.amazon.com/exec/obidos/ASIN/1897636008/icongroupinterna

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Adam, Eve, and the Genome: The Human Genome Project and Theology (Theology and the Sciences) by Susan B. Thistlethwaite (Editor); ISBN: 0800636147; http://www.amazon.com/exec/obidos/ASIN/0800636147/icongroupinterna

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Bibliography ethical legal & social implications of the Human Genome Project (SuDoc E 1.19:0543 T) by Michael S. Yesley; ISBN: B00010D73G; http://www.amazon.com/exec/obidos/ASIN/B00010D73G/icongroupinterna

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Code of Codes: Scientific and Social Issues in the Human Genome Project by Daniel J. Kevles (Editor), Leroy Hood (Editor) (1993); ISBN: 0674136462; http://www.amazon.com/exec/obidos/ASIN/0674136462/icongroupinterna

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Controlling Our Destinies: Historical, Philosophical, Ethical, and Theological Perspectives on the Human Genome Project (Studies in Science and the Humanities from the Reilly Center for Science, tEchnology, and Values, V. 5) by Phillip R. Sloan (Editor) (2000); ISBN: 0268008205; http://www.amazon.com/exec/obidos/ASIN/0268008205/icongroupinterna

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Department of Energy's human genome project issues arising from research : hearing before the Subcommittee on Energy of the Committee on Science, Space, and Technology, House of Representatives, One Hundred Third Congress, second session, October 4, 1994 (SuDoc Y 4.SCI 2:103/173); ISBN: 0160470382; http://www.amazon.com/exec/obidos/ASIN/0160470382/icongroupinterna

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Designing genetic information policy : the need for an independent policy review of the ethical, legal, and social implications of the human genome project : sixteenth report (SuDoc Y 1.1/8:102-478) by U.S. Congressional Budget Office; ISBN: B000109SCU; http://www.amazon.com/exec/obidos/ASIN/B000109SCU/icongroupinterna

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ELSI bibliography ethical, legal, & social implications of the Human Genome Project : 1994 supplement (Sept. 1, 1994) (SuDoc E 1.19:0591/994/SUPP.) by Michael S. Yesley; ISBN: B00010PI8I; http://www.amazon.com/exec/obidos/ASIN/B00010PI8I/icongroupinterna

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Evolution of Sameness and Difference: Perspectives on the Human Genome Project by Stanley Shostak; ISBN: 905702540X; http://www.amazon.com/exec/obidos/ASIN/905702540X/icongroupinterna

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Exons, Introns, and Talking Genes: The Science Behind the Human Genome Project by Christopher Wills; ISBN: 0465021697; http://www.amazon.com/exec/obidos/ASIN/0465021697/icongroupinterna

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Federal technology transfer and the Human Genome Project :; ISBN: 0160482917; http://www.amazon.com/exec/obidos/ASIN/0160482917/icongroupinterna

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Genomics: The Science and Technology Behind the Human Genome Project by Charles R. Cantor (Author), Cassandra L. Smith (Author); ISBN: 0471599085; http://www.amazon.com/exec/obidos/ASIN/0471599085/icongroupinterna

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Guide to the Human Genome Project: Technologies, People, and Institutions (Chemical Heritage Foundation Publication, No. 11) by Susan L. Speaker, et al (1993); ISBN: 0941901106; http://www.amazon.com/exec/obidos/ASIN/0941901106/icongroupinterna

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Human Genome Project by McCun (1992); ISBN: 0865961344; http://www.amazon.com/exec/obidos/ASIN/0865961344/icongroupinterna

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Human Genome Project: Hearing Before the Committee on Science, U.S. House of Representatives by Ken Calvert (Editor) (2000); ISBN: 0756720877; http://www.amazon.com/exec/obidos/ASIN/0756720877/icongroupinterna

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Justice and the Human Genome Project by Timothy F. Murphy (Editor), Marc A. Lappe (Editor); ISBN: 0520083636; http://www.amazon.com/exec/obidos/ASIN/0520083636/icongroupinterna

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Mapping Genetics: An Exploration in Science, Ethics, and Faith: The Human Genome Project As a Case Study by Roger Lincoln Shinn (1996); ISBN: 1559211725; http://www.amazon.com/exec/obidos/ASIN/1559211725/icongroupinterna

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Mapping our genes : federal genome projects : How vast? How fast? : transcript of workshop, "Issues of Collaboration for Human Genome Projects," June 26, 1987 (SuDoc Y 3.T 22/2:2 G 28/3/trans.-2); ISBN: B000108KDS; http://www.amazon.com/exec/obidos/ASIN/B000108KDS/icongroupinterna

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Mapping the Code : The Human Genome Project and the Choices of Modern Science by Joel L. Davis (Author); ISBN: 0471503835; http://www.amazon.com/exec/obidos/ASIN/0471503835/icongroupinterna

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Perilous Knowledge: The Human Genome Project and Its Implications by Tom Wilkie; ISBN: 057117051X; http://www.amazon.com/exec/obidos/ASIN/057117051X/icongroupinterna

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Perspectives on Properties of the Human Genome Project : Advances in Genetics by F. Scott Kieff (Author) (2003); ISBN: 0120176505; http://www.amazon.com/exec/obidos/ASIN/0120176505/icongroupinterna

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Plain Talk About the Human Genome Project: A Tuskegee University Conference on Its Promise and Perils. and Matters of Race by Edward Smith (Editor), et al (1997); ISBN: 1891196014; http://www.amazon.com/exec/obidos/ASIN/1891196014/icongroupinterna

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President's Cancer Panel Meeting the human genome project and disease prediction (SuDoc HE 20.3152:P 92/5/995) by U.S. Dept of Health and Human Services; ISBN: B00010XU6A; http://www.amazon.com/exec/obidos/ASIN/B00010XU6A/icongroupinterna

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The Book of Man: The Human Genome Project and the Quest to Discover Our Genetic Heritage by Walter Bodmer, Robin McKie (Contributor) (1997); ISBN: 0195114876; http://www.amazon.com/exec/obidos/ASIN/0195114876/icongroupinterna

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The Chronology of Science: From Stonehenge to the Human Genome Project by Lisa Rosner (Editor) (2002); ISBN: 1576079546; http://www.amazon.com/exec/obidos/ASIN/1576079546/icongroupinterna

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The Human Genome Project by Daryl MacEr (Editor) (2004); ISBN: 0762303980; http://www.amazon.com/exec/obidos/ASIN/0762303980/icongroupinterna

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The Human Genome Project by Marianne Postiglione (Editor), Robert A. Brungs (1993); ISBN: 0962543160; http://www.amazon.com/exec/obidos/ASIN/0962543160/icongroupinterna

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The Human Genome Project (Library of Future Medicine) by James Toriello; ISBN: 0823936716; http://www.amazon.com/exec/obidos/ASIN/0823936716/icongroupinterna

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The human genome project : hearing before the Subcommittee on Energy Research and Development of the Committee on Energy and Natural Resources, United States Senate, One Hundred First Congress, second session on the human genome project, July 11, 1990 (SuDoc Y 4.En 2:S.hrg.101-894); ISBN: B0001041AE; http://www.amazon.com/exec/obidos/ASIN/B0001041AE/icongroupinterna

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The Human Genome Project and Minority Communities: Ethical, Social, and Political Dilemmas by Raymond A. Zilinskas (Author), Peter J. Balint (Author) (2000); ISBN: 0275969614; http://www.amazon.com/exec/obidos/ASIN/0275969614/icongroupinterna

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The Human Genome Project and the Future of Health Care (Medical Ethics Series) by Thomas H. Murray (Editor), et al (1996); ISBN: 0253332133; http://www.amazon.com/exec/obidos/ASIN/0253332133/icongroupinterna

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The Human Genome Project: Cracking the Code Within Us by Elizabeth L. Marshall; ISBN: 0531158330; http://www.amazon.com/exec/obidos/ASIN/0531158330/icongroupinterna

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The Human Genome Project: Cracking the Genetic Code of Life by Thomas F. Lee; ISBN: 0306439654; http://www.amazon.com/exec/obidos/ASIN/0306439654/icongroupinterna

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The Human Genome Project: Deciphering the Blueprint of Heredity by Necia Grant Cooper (Editor) (1994); ISBN: 0935702296; http://www.amazon.com/exec/obidos/ASIN/0935702296/icongroupinterna

•

The Human Genome Project: What Does Decoding DNA Mean for Us? (Issues in Focus) by Kevin Alexander Boon (2002); ISBN: 0766016854; http://www.amazon.com/exec/obidos/ASIN/0766016854/icongroupinterna

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The Infinite Mind: The Human Genome Project and the Brain by Lichtenstein Creative Media Inc. (1999); ISBN: 1888064552; http://www.amazon.com/exec/obidos/ASIN/1888064552/icongroupinterna

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The New Genetics: The Human Genome Project & Its Impact (Grand Rounds Pr Ser.) by Leon Jaroff; ISBN: 0962474576; http://www.amazon.com/exec/obidos/ASIN/0962474576/icongroupinterna

•

Understanding our genetic inheritance : the U.S. Human Genome Project : the first five years, FY 1991-1995 (SuDoc E 1.19:0452 P) by U.S. Dept of Energy; ISBN: B000109JV0; http://www.amazon.com/exec/obidos/ASIN/B000109JV0/icongroupinterna

•

Understanding The Human Genome Project by Michael A. Palladino (Author); ISBN: 0805367748; http://www.amazon.com/exec/obidos/ASIN/0805367748/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “human genome project” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •

Bibliography--ethical, legal, and social implications of the Human Genome Project Author: Yesley, Michael S.,; Year: 1992; Washington, D.C.: U.S. Dept. of Energy, Office of Energy Research; Springfield, VA: Available from the National Technical Information Service, U.S. Dept. of Commerce, [1992]

•

Understanding our genetic inheritance: the U.S. Human Genome Project: the first five years, FY 1991-1995. Author: National Center for Human Genome Research (U.S.); Year: 1989; [Bethesda, Md.]: U.S. Dept. of Health and

10

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Chapters on Human Genome Project In order to find chapters that specifically relate to human genome project, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and human genome project using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “human genome project” (or synonyms) into the “For these words:” box.

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CHAPTER 7. MULTIMEDIA ON HUMAN GENOME PROJECT Overview In this chapter, we show you how to keep current on multimedia sources of information on human genome project. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Bibliography: Multimedia on Human Genome Project The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in human genome project (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on human genome project: •

From the double helix to the Human Genome Project [videorecording] Source: Medical Arts and Photography Branch; Year: 1998; Format: Videorecording; [Bethesda, Md.: National Institutes of Health, 1998]

•

The Human Genome Project [electronic resource]: science, law, and social change in the 21st century Source: Whitehead Policy Symposium; Year: 1998; Format: Electronic resource; [Cambridge, Mass.]: Whitehead Institute for Biomedical Research; [Boston, Mass.]: American Society of Law, Medicine & Ethics, c1998

•

The human genome project [kit]: exploring our molecular selves Source: produced by National Human Genome Research Institute, National Institutes of Health; Year: 2001; Format: Kit; [Bethesda, Md.]: National Institutes of Health, [2001?]

•

The Human Genome Project [videorecording] Source: a production of the Stanford Alumni Association and the Stanford Centennial Operating Committee; Year: 1991; Format: Videorecording; Stanford, CA: Stanford Alumni Association, c1991

•

The Human Genome Project [videorecording] Source: a production of the National Center for Human Genome Research, U.S. Department of Health and Human Services; Year: 1989; Format: Videorecording; [Bethesda, Md.]: The Center, [1989?]

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The Human Genome Project [videorecording]: problems and prospects Source: Charles Cantor; Year: 1988; Format: Videorecording; [Bethesda, MD]: National Library of Medicine, 1988

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The Human Genome Project [videorecording]: what are we hoping to learn? Source: Eric Lander; Year: 1988; Format: Videorecording; [Bethesda, MD]: National Library of Medicine, 1988

•

The societal implications of the Human Genome Project [videorecording] Source: produced by Armed Forces Institute of Pathology and American Registry of Pathology; Year: 1993; Format: Videorecording; Washington, D.C.: The Institute, [1993]

•

Understanding our genetic inheritance [electronic resource]: the U.S. Human Genome Project, the first five years: fiscal years 1991-1995. Year: 2000; Format: Electronic resource; [Bethesda, Md.?]: National

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CHAPTER 8. PERIODICALS AND NEWS ON HUMAN GENOME PROJECT Overview In this chapter, we suggest a number of news sources and present various periodicals that cover human genome project.

News Services and Press Releases One of the simplest ways of tracking press releases on human genome project is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “human genome project” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to human genome project. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “human genome project” (or synonyms). The following was recently listed in this archive for human genome project: •

Human genome project completed Source: Reuters Industry Breifing Date: April 14, 2003

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Human Genome Project director peers into the future Source: Reuters Industry Breifing Date: January 19, 2001

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"Human Genome Project of cell signaling" launched Source: Reuters Health eLine Date: September 22, 2000

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Scientists launch the "Human Genome Project of cell signaling" Source: Reuters Industry Breifing Date: September 21, 2000

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Human Genome Project still on track to finish map of genome by 2003 Source: Reuters Health eLine Date: September 12, 2000

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Human Genome Project still on track to complete final map of genome by 2003 Source: Reuters Industry Breifing Date: September 12, 2000

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Human Genome Project, SNP Consortium collaborate Source: Reuters Health eLine Date: July 12, 2000

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Human Genome Project, SNP Consortium collaborate on new genetic markers Source: Reuters Industry Breifing Date: July 12, 2000

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Celera sequences entire human genome; Human Genome Project not far behind Source: Reuters Industry Breifing Date: June 27, 2000

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Human Genome Project director calls for immediate legislation on genomics Source: Reuters Medical News Date: June 07, 2000

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Human Genome Project is opening new avenues of genomics research Source: Reuters Medical News Date: April 10, 2000

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Human Genome Project two thirds complete Source: Reuters Medical News Date: March 31, 2000

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Human Genome Project in the home-stretch Source: Reuters Health eLine Date: March 30, 2000 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine.

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Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “human genome project” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “human genome project” (or synonyms). If you know the name of a company that is relevant to human genome project, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “human genome project” (or synonyms).

Newsletters on Human Genome Project Find newsletters on human genome project using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “human genome project.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “human genome project” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

Human Genome Project Progress Source: GIG Newsletter. Gluten Intolerance Group of North America Newsletter. 17(2): 4-5. April-June 1993.

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Contact: Available from Gluten Intolerance Group of North America. P.O. Box 23053, Seattle, WA 98102. (206) 325-6980. Summary: This Gluten Intolerance Group (GIG) newsletter article condenses information from a recent report from the Human Genome Project of the National Center for Human Genome Research (NCHGR). The article describes the scientific aims of the Human Genome Project; the activities of the NCHGR; outreach programs of human genome centers; the nine genome centers of the NCHGR; and projects of these centers that might be of particular interest to members of GIG. The introduction notes that, since celiac sprue and dermatitis herpetiformis are genetic disorders, any information gleaned about the gene(s) that code for these disorders will help determine cause and perhaps provide information for treatment and cure.

Academic Periodicals covering Human Genome Project Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to human genome project. In addition to these sources, you can search for articles covering human genome project that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

11

These publications are typically written by one or more of the various NIH Institutes.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

12

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.

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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “human genome project” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 3401 606 261 5 6 4279

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “human genome project” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

15

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

19 Adapted 20

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on human genome project can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to human genome project. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to human genome project. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “human genome project”:

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•

Other guides Cloning http://www.nlm.nih.gov/medlineplus/cloning.html Genes and Gene Therapy http://www.nlm.nih.gov/medlineplus/genesandgenetherapy.html Genetic Disorders http://www.nlm.nih.gov/medlineplus/geneticdisorders.html Genetic Testing/Counseling http://www.nlm.nih.gov/medlineplus/genetictestingcounseling.html Huntington's Disease http://www.nlm.nih.gov/medlineplus/huntingtonsdisease.html

Within the health topic page dedicated to human genome project, the following was listed: •

General/Overviews Gene Therapy Source: Dept. of Energy http://www.ornl.gov/TechResources/Human_Genome/medicine/genetherapy.ht ml Introduction to Genetics and Genetic Testing Source: Nemours Foundation http://kidshealth.org/parent/system/medical/genetics.html JAMA Patient Page: Genetics Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZZCI25TTC&s ub_cat=202

•

Specific Conditions/Aspects Cloning Source: Dept. of Energy http://www.ornl.gov/sci/techresources/Human_Genome/elsi/cloning.shtml Genes and Populations Source: National Institute of General Medical Sciences http://www.nigms.nih.gov/news/science_ed/genepop/faq.html Human Gene Therapy: Harsh Lessons, High Hopes Source: Food and Drug Administration http://www.fda.gov/fdac/features/2000/500_gene.html Medicine and the New Genetics: Gene Testing, Pharmacogenomics, and Gene Therapy Source: Dept. of Energy, Human Genome Project http://www.ornl.gov/TechResources/Human_Genome/publicat/primer2001/6.ht ml

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Your Genes, Your Choices: Exploring the Issues Raised by Genetic Research Source: American Association for the Advancement of Science, Dept. of Energy http://www.ornl.gov/TechResources/Human_Genome/publicat/genechoice/ind ex.html •

Children Gene Therapy and Your Child Source: Nemours Foundation http://kidshealth.org/parent/system/medical/gene_therapy.html What is a Gene? Source: Nemours Foundation http://kidshealth.org/kid/talk/qa/what_is_gene.html You and Your Genes: Making It in a Tough Environment Source: National Institute of Environmental Health Sciences http://www.niehs.nih.gov/oc/factsheets/genes/home.htm

•

From the National Institutes of Health Frequently Asked Questions about Genetics Source: National Human Genome Research Institute http://www.genome.gov/page.cfm?pageID=10001191 Genetics Home Reference Source: National Library of Medicine http://ghr.nlm.nih.gov/ Human Genome Project Source: National Human Genome Research Institute http://www.genome.gov/page.cfm?pageID=10001694 Questions and Answers about Gene Therapy Source: National Cancer Institute http://cis.nci.nih.gov/fact/7_18.htm

•

Journals/Newsletter Genomics Weekly Update Source: Centers for Disease Control and Prevention http://www.cdc.gov/genomics/update/current.htm

•

Latest News Beyond Genes: Scientists Venture Deeper Into the Human Genome Source: 10/09/2003, National Human Genome Research Institute http://www.nih.gov/news/pr/oct2003/nhgri-09.htm Gene Found As Definitive Cause of Heart Attacks Source: 11/28/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14880 .html

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Gene Mutation Causes Arthritis in Mice Source: 11/26/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14873 .html More News on Genes and Gene Therapy http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/alphanews_g.html#G enesandGeneTherapy Study Links Genetic, Non-inherited Breast Cancer Source: 11/25/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14834 .html •

Law and Policy Genetics Privacy and Legislation Source: Dept. of Energy http://www.ornl.gov/TechResources/Human_Genome/elsi/legislat.html Human Gene Therapy and the Role of the Food and Drug Administration Source: Food and Drug Administration http://www.fda.gov/cber/infosheets/genezn.htm Issues in Genetics and Health Source: National Human Genome Research Institute http://www.genome.gov/page.cfm?pageID=10001740

•

Organizations GeneTests Source: Children's Health Care System, Seattle http://www.genetests.org/ Human Genome Project Information Source: Dept. of Energy http://www.ornl.gov/TechResources/Human_Genome/home.html National Human Genome Research Institute http://www.genome.gov/ National Reference Center for Bioethics Literature http://www.georgetown.edu/research/nrcbl/nrc/

•

Research Beyond Genes: Scientists Venture Deeper Into the Human Genome Source: National Human Genome Research Institute http://www.nih.gov/news/pr/oct2003/nhgri-09.htm Facts about Genome Sequencing Source: Dept. of Energy http://www.ornl.gov/TechResources/Human_Genome/faq/seqfacts.html Functional and Comparative Genomics Source: Dept. of Energy http://www.ornl.gov/TechResources/Human_Genome/faq/compgen.html

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Gene Therapy to Treat Angina Appears Safe Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3000956 Mouse Genome and the Measure of Man Source: National Human Genome Research Institute http://www.genome.gov/page.cfm?pageID=10005831 Mutations in DNA Mismatch Repair Genes Source: American College of Physicians http://www.annals.org/cgi/content/full/138/7/I-53 New Bioinformatics Tool Will Help Design Cancer Drugs Source: National Cancer Institute http://www.cancer.gov/newscenter/weinstein Newly Identified Tumor Suppressor Cooperates with p53 to Protect Mice against Tumors Source: National Cancer Institute http://www.nih.gov/news/pr/aug2003/nci-07.htm NHGRI Study May Help Scientists Design Safer Methods for Gene Therapy Source: National Human Genome Research Institute http://www.nih.gov/news/pr/jun2003/nhgri-12.htm Only Two Genes Needed to Form Heads in Model Organism Embryos Source: National Institute of General Medical Sciences http://www.nigms.nih.gov/news/releases/brief_solnica-krezel.html Progress Made in Sequencing of Model Organisms' Genomes Source: National Human Genome Research Institute http://www.nih.gov/news/pr/may2003/nhgri-20.htm Research Brief: A Protein to Tie Up Loose Ends Source: National Institute of General Medical Sciences http://www.nigms.nih.gov/news/releases/brief_lieber.html Researchers Discover Use of Novel Mechanism Preserves Y Chromosome Genes Source: National Human Genome Research Institute http://www.nih.gov/news/pr/jun2003/nhgri-18.htm Scientists Glimpse Cellular Machines at Work Inside Living Cells Source: National Cancer Institute http://www.cancer.gov/newscenter/pressreleases/machines Scientists Pinpoint Gene Influencing Age-at-Onset Parkinsonâ€™s Source: National Institute on Aging http://www.nia.nih.gov/news/pr/2003/1021b.htm

of

Alzheimerâ€™s,

SNP (Single Nucleotide Polymorphisms) Source: Dept. of Energy http://www.ornl.gov/TechResources/Human_Genome/faq/snps.html Study Finds Direction of Enzymes Affects DNA Repair Source: National Institute of Environmental Health Sciences http://www.niehs.nih.gov/oc/news/wilsdna.htm

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•

Teenagers Basics on Genes and Genetic Disorders Source: Nemours Foundation http://kidshealth.org/teen/your_body/health_basics/genes_genetic_disorders.ht ml

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on human genome project. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Brain Concepts: Genes and the Brain Source: Washington, DC: Society for Neuroscience. 1992. 4 p. Contact: Society for Neuroscience. 11 Dupont Circle, NW, Suite 500, Washington, DC 20036. (202) 462-6688. PRICE: 50 cents each, sent in eight title bundles, $4.00. Summary: This fact sheet discusses the role of genetic research in the identification and development of potential therapies for brain diseases and explains the Human Genome Project. Scientists have identified 20 neurological disorders and the chromosomal location of the defect in 50 to 100 of them. Gene mapping has led to the localization on chromosome 21 of the gene coding the beta amyloid precursor, the protein that is cut abnormally to form the smaller peptide, beta amyloid. It is this peptide that accumulates in plaques in Alzheimer's disease. New molecular genetic technology has allowed the development of animal models of genetic diseases that help scientists better understand many brain disorders. Potential therapies to the brain are being generated through genetic engineering techniques. This fact sheet highlights additional scientific advancements, such as the development of immortalized neurons and the cloning and sequencing of genes resulting in new treatments such as the rational drug design. Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:

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From Maps to Medicine: About the Human Genome Research Project Summary: The Human Genome Project is an ambitious effort to understand the hereditary instructions that make each of us unique. Source: National Human Genome Research Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1011

•

Human Genome Project: Exploring our Molecular Selves Summary: A free multimedia kit for use as an educational tool for high school students and the general public. Source: National Human Genome Research Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6055 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to human genome project. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to human genome project. By consulting all of

126 Human Genome Project

associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with human genome project. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about human genome project. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “human genome project” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “human genome project”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “human genome project” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “human genome project” (or a synonym) into the search box, and click “Submit Query.”

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129

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

22

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

23

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

134 Human Genome Project

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

135

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

137

HUMAN GENOME PROJECT DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abductor: A muscle that draws a part away from the median line. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Adenomatous Polyposis Coli: An autosomal dominant polyposis syndrome in which the colon contains few to thousands of adenomatous polyps, often occurring by age 15 to 25. [NIH]

Adolescent Medicine: A branch of medicine pertaining to the diagnosis and treatment of diseases occurring during the period beginning with puberty until the cessation of somatic growth. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH]

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Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]

Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthesiology: A specialty concerned with the study of anesthetics and anesthesia. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH]

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Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Anthropology: The science devoted to the comparative study of man. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Aqueous: Having to do with water. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH]

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Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Articular: Of or pertaining to a joint. [EU] Artificial Organs: Devices intended to replace non-functioning organs. They may be temporary or permanent. Since they are intended always to function as the natural organs they are replacing, they should be differentiated from prostheses and implants and specific types of prostheses which, though also replacements for body parts, are frequently cosmetic (artificial eye) as well as functional (artificial limbs). [NIH] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Asbestosis: A lung disorder caused by constant inhalation of asbestos particles. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]

Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biological Sciences: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from biology, one of its subdivisions, concerned

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specifically with the origin and life processes of living organisms. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Calcium: A basic element found in nearly all organized tissues. It is a member of the

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alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are

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made up of one or more cells. [NIH] Cell Division: The fission of a cell. [NIH] Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Segregation: The orderly segregation of chromosomes during meiosis or mitosis. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH]

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Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials

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including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or

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treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cosmids: Plasmids containing at least one cos (cohesive-end site) of phage lambda. They are used as cloning vehicles for the study of aberrant eukaryotic structural genes and also as genetic vectors for introducing the nucleic acid of transforming viruses into cultured cells. [NIH]

Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Critical Illness: A disease or state in which death is possible or imminent. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH]

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Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dilatation: The act of dilating. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Dissection: Cutting up of an organism for study. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the

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extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]

Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location

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of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]

Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinologist: A doctor that specializes in diagnosing and treating hormone disorders. [NIH]

Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]

Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Estrogen: One of the two female sex hormones. [NIH] Eugenic: Tending to improve the genetic qualities of future generations. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expressed Sequence Tags: Sequence tags derived from cDNAs. Expressed sequence tags (ESTs) are partial DNA sequences from clones. [NIH] Extracellular: Outside a cell or cells. [EU]

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Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Practice: A medical specialty concerned with the provision of continuing, comprehensive primary health care for the entire family. [NIH] Fat: Total lipids including phospholipids. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal Neoplasms: Tumors or cancer of the gastrointestinal system. [NIH]

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Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Order: The sequential location of genes on a chromosome. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetic Vectors: Any DNA molecule capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from plasmids, bacteriophages or viruses. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain genetic markers to facilitate their selective recognition. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH]

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Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH]

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Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Genome Project: A coordinated effort of researchers to map and sequence the human genome. [NIH] Human Rights: The rights of the individual to cultural, social, economic, and educational opportunities as provided by society, e.g., right to work, right to education, and right to social security. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type

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IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Immersion: The placing of a body or a part thereof into a liquid. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

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Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

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Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Lod: The lowest analyte content which, if actually present, will be detected with reasonable statistical certainty and can be identified according to the identification criteria of the method. If both accuracy and precision are constant over a concentration range. [NIH] Lod Score: The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds." [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen,

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thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those

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persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motivations: The most compelling inner determinants of human behavior; also called drives, urges, impulses, needs, wants, tensions, and willful cravings. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH]

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NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurosurgeon: A doctor who specializes in surgery on the brain, spine, and other parts of the nervous system. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]

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Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oncogenes: Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have prefix "v-" before the gene symbol; cellular oncogenes (protooncogenes) have the prefix "c-" before the gene symbol. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orderly: A male hospital attendant. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parturition: The act or process of given birth to a child. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Care Team: Care of patients by a multidisciplinary team usually organized under the leadership of a physician; each member of the team has specific responsibilities and the

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whole team contributes to the care of the patient. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pediatric Gastroenterologist: A doctor who treats children with digestive diseases. [NIH] Pelvic: Pertaining to the pelvis. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Philately: Study of stamps or postal markings. It usually refers to the design and commemorative aspects of the stamp. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of

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organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU]

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Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Problem-Based Learning: Instructional use of examples or cases to teach using problemsolving skills and critical thinking. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU]

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Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Public Sector: The area of a nation's economy that is tax-supported and under government control. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

P-value: A statistics term. A measure of probability that a difference between groups during an experiment happened by chance. For example, a p-value of .01 (p = .01) means there is a 1 in 100 chance the result occurred by chance. The lower the p-value, the more likely it is that the difference between groups was caused by treatment. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH]

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Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Robotics: The application of electronic, computerized control systems to mechanical devices designed to perform human functions. Formerly restricted to industry, but nowadays applied to artificial organs controlled by bionic (bioelectronic) devices, like automated insulin pumps and other prostheses. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Scrapie: A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called prions. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and

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their contained allelomorphic gene pairs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencer: Device that reads off the order of nucleotides in a cloned gene. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Social Change: Social process whereby the values, attitudes, or institutions of society, such as education, family, religion, and industry become modified. It includes both the natural process and action programs initiated by members of the community. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU]

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Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stridor: The loud, harsh, vibrating sound produced by partial obstruction of the larynx or trachea. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may

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be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Technology Transfer: Spread and adoption of inventions and techniques from one geographic area to another, from one discipline to another, or from one sector of the economy to another. For example, improvements in medical equipment may be transferred from industrial countries to developing countries, advances arising from aerospace engineering may be applied to equipment for persons with disabilities, and innovations in science arising from government research are made available to private enterprise. [NIH] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Testicular: Pertaining to a testis. [EU] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances

Dictionary 169

usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tracheostomy: Surgical formation of an opening into the trachea through the neck, or the opening so created. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translating: Conversion from one language to another language. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary

170 Human Genome Project

artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH]

171

INDEX A Abductor, 28, 137 Aberrant, 96, 137, 146 Acute myelogenous leukemia, 15, 137 Acute myeloid leukemia, 137 Acute nonlymphocytic leukemia, 137 Adenomatous Polyposis Coli, 65, 137 Adolescent Medicine, 45, 137 Adrenergic, 137, 148, 149, 168 Adverse Effect, 137, 166 Aggressiveness, 12, 137 Agonist, 137, 148 Airway, 26, 28, 137 Airway Obstruction, 28, 137 Algorithms, 10, 12, 21, 26, 31, 35, 137, 141 Alleles, 16, 96, 137, 156 Alternative medicine, 109, 137 Alternative Splicing, 10, 21, 26, 31, 138, 163 Amino Acid Motifs, 138, 145 Amino Acid Sequence, 89, 138, 139, 145, 149, 151 Amino Acids, 138, 145, 151, 161, 162, 163 Amplification, 11, 19, 138 Amyloid, 124, 138 Anal, 12, 138 Analgesic, 138, 149 Analogous, 138, 148, 169 Androgens, 138, 139 Anemia, 15, 22, 138, 150 Anesthesia, 137, 138 Anesthesiology, 47, 138 Anesthetics, 138, 149 Animal model, 5, 9, 124, 138 Anisotropy, 139, 150 Annealing, 139, 162 Anomalies, 9, 87, 139 Anthrax, 11, 139 Anthropology, 14, 66, 139 Antibacterial, 139, 167 Antibiotic, 139, 167 Antibodies, 97, 139, 140, 162 Antibody, 139, 144, 150, 153, 154 Antigen, 139, 144, 150, 153, 154 Antiviral, 139, 161 Anus, 138, 139 Apolipoproteins, 139, 156 Aqueous, 139, 140

Aromatase, 40, 139 Arterial, 139, 143, 153, 163 Arteries, 139, 140, 141, 146, 156, 158 Arterioles, 140, 141, 142 Articular, 17, 140 Artificial Organs, 140, 165 Asbestos, 36, 140 Asbestosis, 140 Assay, 5, 24, 25, 140 Autoantibodies, 140, 147 Axonal, 8, 140 B Bacillus, 139, 140 Bacteria, 139, 140, 158, 167 Bacterium, 140, 144 Basal Ganglia, 140, 141 Base, 6, 7, 16, 33, 140, 147, 151, 155 Behavioral Symptoms, 20, 140 Beta-pleated, 138, 140 Bile, 140, 156, 167 Biochemical, 16, 23, 57, 72, 75, 137, 140 Biochemical reactions, 23, 140 Biological Sciences, 28, 54, 58, 140 Biomarkers, 26, 36, 141 Biophysics, 140, 141 Biotechnology, 13, 17, 37, 39, 40, 41, 43, 45, 46, 49, 57, 59, 61, 80, 103, 109, 115, 141 Bladder, 141, 159, 163, 169 Blood pressure, 141, 142, 153, 158 Blood vessel, 141, 142, 143, 156, 157, 166, 168, 169 Blot, 15, 141 Body Fluids, 141, 169 Bone Marrow, 15, 137, 141, 154, 156, 158, 166, 167 Bone scan, 141, 165 Bowel, 138, 141, 155, 159 Brain Diseases, 124, 141 Branch, 105, 133, 137, 141, 157, 160, 164, 167, 168 Bronchi, 141, 149, 169 Bronchial, 26, 141 Buccal, 141, 156 Bullous, 141, 147 C Calcium, 140, 141, 144 Callus, 142, 148 Capillary, 7, 23, 142, 170

172 Human Genome Project

Carbohydrate, 142, 166 Carcinogen, 27, 142 Carcinogenesis, 27, 142, 143 Carcinogenic, 142, 155, 163, 167 Cardiac, 49, 87, 142, 149, 158, 167 Cardiology, 41, 60, 142 Cardiovascular, 49, 96, 142 Cardiovascular disease, 96, 142 Case report, 142, 143 Case series, 142, 143 Case-Control Studies, 96, 142 Catecholamine, 142, 147 Causality, 24, 142 Cell Division, 140, 143, 152, 157, 158, 161, 165 Cell Polarity, 5, 143 Cell proliferation, 143, 160 Cell Transplantation, 143 Central Nervous System, 141, 143, 147, 151, 158 Cerebellum, 141, 143 Cerebral, 140, 141, 143, 148, 149, 150 Cerebrovascular, 142, 143 Character, 143, 147 Chemoprevention, 27, 143 Chemopreventive, 26, 143 Cholesterol, 18, 140, 143, 146, 148, 153, 156, 167 Cholesterol Esters, 143, 156 Chromosomal, 8, 19, 28, 124, 138, 143 Chromosome, 5, 6, 9, 20, 51, 123, 124, 143, 151, 156, 165 Chromosome Segregation, 5, 143 Chronic, 143, 147, 154, 168 Chylomicrons, 143, 156 CIS, 121, 143 Cleft Palate, 99, 143 Clinical Medicine, 65, 68, 70, 75, 143, 162 Clinical study, 19, 143 Clinical trial, 4, 27, 115, 143, 144, 164 Clone, 15, 25, 144 Cloning, 10, 15, 19, 28, 120, 124, 141, 144, 146 Cluster Analysis, 35, 144 Coenzyme, 144, 150 Cofactor, 144, 163 Collagen, 144, 150 Colloidal, 144, 148 Colorectal, 24, 144 Colorectal Cancer, 24, 144 Competency, 80, 144 Complement, 144, 145, 151, 157

Complementary and alternative medicine, 85, 91, 145 Complementary medicine, 85, 145 Complementation, 15, 145 Computational Biology, 35, 36, 115, 145 Computed tomography, 145, 165 Computer Simulation, 12, 145 Computerized axial tomography, 145, 165 Connective Tissue, 141, 144, 145, 150, 165 Consensus Sequence, 23, 138, 145 Conserved Sequence, 138, 145 Contraindications, ii, 145 Coronary, 18, 55, 142, 146, 158 Coronary heart disease, 55, 142, 146 Coronary Thrombosis, 146, 158 Cortex, 86, 141, 146, 150 Cortical, 11, 146 Cosmids, 97, 146 Critical Care, 36, 43, 146 Critical Illness, 36, 146 Crossing-over, 146, 164 Cultured cells, 146 Curative, 38, 146, 168 Cutaneous, 139, 146, 156 Cytochrome, 139, 146 Cytokine, 36, 146 D Data Collection, 5, 146, 150 Databases, Bibliographic, 115, 146 Degenerative, 8, 147 Deletion, 9, 15, 147 Denaturation, 147, 162 Dendrites, 147, 159 Density, 9, 30, 147, 148, 156, 160 Dental Care, 100, 147 Dentists, 3, 147 Dermatitis, 110, 147 Dermatitis Herpetiformis, 110, 147 Developing Countries, 147, 168 Dextroamphetamine, 147, 158 Diagnostic procedure, 95, 109, 147 Digestion, 140, 141, 147, 155, 156 Dilatation, 147, 163 Diploid, 145, 147, 162 Direct, iii, 6, 15, 28, 143, 147, 148, 164 Discrimination, 25, 62, 87, 147 Disease Susceptibility, 16, 33, 147 Dissection, 78, 86, 147 Distal, 8, 140, 147, 163 Dopamine, 27, 147 Drive, ii, vi, 23, 81, 148 Drug Design, 124, 148

Index 173

Drug Interactions, 148 Dwarfism, 88, 148 Dyes, 138, 148 Dyslipidemia, 18, 148 E Efficacy, 26, 148 Electrons, 140, 148, 155, 164 Electrophoresis, 9, 23, 29, 148 Embryo, 5, 148, 150, 163 Embryogenesis, 5, 148 Embryology, 99, 148 Encephalocele, 148, 159 Endemic, 149, 167 Endocrine System, 149 Endocrinologist, 74, 149 Endocrinology, 40, 54, 149, 152 Endorphin, 29, 149 Environmental Health, 86, 88, 89, 114, 116, 121, 123, 149 Enzymatic, 142, 145, 149, 162 Enzyme, 139, 144, 148, 149, 158, 162, 164, 170 Epidemic, 149, 167 Epinephrine, 137, 147, 149, 159, 169 Epithelial, 27, 149 Epithelial Cells, 27, 149 Epithelium, 26, 149 Erythrocytes, 138, 141, 149 Estrogen, 139, 149 Eugenic, 65, 149 Eukaryotic Cells, 149, 154 Exogenous, 149, 151, 161 Exon, 138, 149 Expressed Sequence Tags, 11, 13, 44, 149 Extracellular, 138, 145, 149, 150 Extracellular Matrix, 145, 150 Extrapyramidal, 148, 150 F Family Planning, 115, 150 Family Practice, 51, 77, 150 Fat, 141, 146, 150, 156, 165, 166 Febrile, 150, 167 Fetal Development, 150, 159 Fetus, 150, 161, 162, 163 Fibroblasts, 17, 150 Fibrosis, 34, 50, 82, 150 Fissure, 143, 150 Fluorescence, 9, 19, 25, 150 Fluorescence Polarization, 25, 150 Focus Groups, 6, 150 Folate, 150 Fold, 18, 23, 30, 150

Folic Acid, 78, 82, 100, 150 Fungi, 150, 152, 158, 170 G Gastrointestinal, 140, 149, 150, 169 Gastrointestinal Neoplasms, 140, 150 Gene Expression, 9, 12, 17, 28, 151 Gene Order, 20, 151 Gene Targeting, 16, 151 Genetic Code, 102, 151, 160 Genetic Counseling, 20, 100, 151 Genetic Engineering, 10, 89, 124, 141, 144, 151 Genetic Markers, 9, 12, 108, 151 Genetic Screening, 3, 34, 151 Genetic testing, 4, 10, 13, 20, 33, 34, 38, 151, 162 Genetic Vectors, 146, 151 Genital, 151, 152 Genomics, 4, 5, 6, 9, 10, 14, 15, 21, 26, 30, 31, 35, 36, 38, 43, 44, 58, 62, 63, 79, 97, 101, 108, 121, 122, 151 Genotype, 6, 12, 15, 48, 151, 161 Gland, 151, 160, 163, 165, 167 Glutamic Acid, 150, 151 Goats, 151, 165 Governing Board, 152, 162 Gp120, 152, 161 Grade, 14, 152 Graft, 4, 152, 153, 154 Graft Rejection, 152, 154 Granulocytes, 152, 155, 170 Grasses, 150, 152 Growth, 137, 138, 139, 143, 147, 148, 150, 152, 157, 159, 160, 161 Growth factors, 152, 160 Gynecology, 55, 69, 74, 152 H Haplotypes, 12, 20, 152 Health Behavior, 66, 152 Health Education, 21, 66, 152 Health Status, 152 Heart attack, 142, 152 Hemoglobin, 138, 149, 152 Hemorrhage, 153, 168 Hereditary, 28, 33, 125, 153 Heredity, 103, 151, 153 Heritability, 28, 153 Heterogeneity, 8, 12, 153 Homeostasis, 18, 153 Homogeneous, 25, 153 Homologous, 20, 137, 146, 151, 153, 163, 165

174 Human Genome Project

Hormone, 54, 148, 149, 153, 155, 165 Host, 33, 151, 153, 154 Human Rights, 153 Hybrid, 24, 144, 153 Hybridization, 9, 15, 18, 153 Hydrogen, 140, 142, 147, 153, 158, 160 Hydrophobic, 153, 156 Hypercholesterolemia, 148, 153 Hyperlipidemia, 18, 148, 153 Hypersensitivity, 153, 165 Hypertension, 142, 153 Hypertriglyceridemia, 148, 153 Hypothalamus, 141, 154 I Id, 83, 90, 125, 132, 134, 154 Immersion, 36, 154 Immune system, 154, 157, 170 Immunization, 154 Immunologic, 154, 157 Immunosuppressive, 154 Immunosuppressive therapy, 154 Immunotherapy, 12, 154 Impairment, 154, 157 In situ, 9, 28, 154 In Situ Hybridization, 9, 28, 154 In vitro, 154, 162 In vivo, 5, 154 Incubation, 16, 154 Indicative, 100, 154, 160, 169 Infarction, 146, 154, 158 Infection, 4, 16, 139, 154, 156, 165, 168, 170 Inflammation, 147, 150, 155, 165 Ingestion, 139, 155 Initiation, 26, 33, 155, 169 Inotropic, 148, 155 Insight, 18, 29, 155 Insulin, 155, 165 Internal Medicine, 25, 45, 66, 149, 155 Interstitial, 9, 155 Intestine, 141, 144, 153, 155 Intracellular, 143, 154, 155 Ions, 140, 153, 155 J Joint, 23, 39, 140, 155, 168 K Kb, 30, 114, 155 L Language Disorders, 100, 155 Large Intestine, 144, 155, 164 Laryngeal, 28, 155 Larynx, 155, 167, 169 Latent, 155, 162

Lesion, 155, 156 Lethal, 36, 155 Leucocyte, 53, 155 Leukemia, 80, 156 Leukocytes, 141, 152, 156 Library Services, 132, 156 Ligament, 156, 163 Linkage, 6, 8, 12, 15, 18, 19, 27, 28, 33, 96, 151, 156 Linkage Disequilibrium, 12, 27, 28, 97, 156 Lip, 99, 156 Lipid, 139, 155, 156 Lipoprotein, 18, 148, 156 Liver, 88, 140, 150, 156, 165 Liver scan, 156, 165 Localization, 124, 156 Localized, 29, 30, 154, 156, 161 Locomotor, 156, 165 Lod, 6, 156 Lod Score, 6, 156 Low-density lipoprotein, 148, 156 Lupus, 32, 156 Lymphatic, 154, 156, 166 Lymphatic system, 156, 166 Lymphoid, 139, 155, 157 Lymphokines, 157 M Macrophage, 17, 157 Macrophage Activation, 17, 157 Magnetic Resonance Imaging, 157, 165 Major Histocompatibility Complex, 152, 157 Malignancy, 6, 15, 157 Malignant, 9, 157 Manifest, 140, 157 Mediate, 148, 157 MEDLINE, 115, 157 Megaloblastic, 150, 157 Meiosis, 143, 157 Membrane, 97, 143, 145, 149, 150, 152, 155, 157, 158, 161, 162, 169 Mental Disorders, 157, 164 Mental Health, iv, 4, 22, 114, 116, 157, 164 Mental Retardation, 8, 60, 65, 157 Mentors, 34, 157 Metabolic disorder, 96, 158 Metaphase, 18, 158 Methylphenidate, 27, 158 MI, 135, 158 Micro-organism, 80, 158 Microscopy, 5, 86, 158 Migration, 157, 158

Index 175

Mitosis, 143, 158 Modeling, 12, 22, 148, 158 Modification, 151, 158, 164 Molecule, 16, 139, 140, 144, 151, 152, 158, 160, 164 Monitor, 7, 158, 159 Morphological, 148, 158 Morphology, 157, 158 Motivations, 24, 158 Mucosa, 156, 158 Myelin, 158, 166 Myelogenous, 158 Myocardium, 158 N Narcolepsy, 147, 158 NCI, 1, 26, 113, 121, 123, 143, 159 Necrosis, 154, 158, 159 Need, 3, 7, 9, 16, 19, 22, 24, 35, 99, 101, 104, 109, 126, 159 Neoplastic, 159, 160 Nerve, 8, 137, 138, 140, 147, 159, 167, 169 Nervous System, 143, 159, 165, 168 Networks, 17, 22, 24, 159 Neural, 78, 82, 138, 149, 159 Neural tube defects, 78, 82, 159 Neurologic, 72, 149, 159 Neurology, 8, 63, 72, 78, 88, 159 Neuronal, 86, 159 Neurons, 124, 147, 159, 168 Neurosurgeon, 88, 159 Neurosurgery, 55, 159 Norepinephrine, 137, 147, 159 Nuclear, 20, 94, 140, 148, 149, 159, 160, 168 Nuclei, 148, 151, 157, 158, 159 Nucleic acid, 97, 146, 151, 153, 154, 160, 163 Nucleic Acid Hybridization, 153, 160 Nucleus, 68, 149, 157, 160, 167 O Obstetrics, 55, 69, 74, 160 Oligo, 30, 160 Oncogenes, 18, 26, 160, 163 Opacity, 147, 160 Oral Health, 4, 160 Orderly, 143, 160 Orofacial, 100, 160 Ovaries, 139, 160, 166 P Palate, 99, 143, 160 Palliative, 160, 168 Pancreas, 141, 155, 160, 169 Paralysis, 28, 160

Parturition, 160 Pathogen, 154, 160 Pathogenesis, 15, 160 Pathologic, 141, 146, 153, 160 Pathophysiology, 29, 160 Patient Care Team, 100, 160 Patient Education, 124, 130, 132, 135, 161 Pediatric Gastroenterologist, 76, 161 Pelvic, 161, 163 Peptide, 124, 161, 162, 163 Peptide T, 124, 161 Perception, 67, 161 Periodontal disease, 4, 161 Perioperative, 47, 161 Peripheral blood, 17, 161 Pharmacokinetics, 148, 161 Pharmacologic, 138, 161, 169 Phenotype, 5, 8, 15, 17, 28, 32, 37, 48, 96, 145, 161 Philately, 47, 161 Phospholipids, 150, 156, 161 Physiologic, 137, 150, 161, 164 Physiology, 11, 47, 53, 140, 142, 149, 152, 161 Placenta, 139, 161, 164 Plants, 140, 158, 159, 161, 169 Plasma, 18, 139, 143, 152, 162, 166 Plasma cells, 139, 162 Polymerase, 11, 162 Polymerase Chain Reaction, 11, 162 Polymorphic, 8, 28, 162 Polymorphism, 6, 16, 20, 25, 27, 28, 30, 96, 162 Polypeptide, 138, 144, 145, 153, 162, 163 Polyposis, 137, 144, 162 Posterior, 138, 143, 160, 162 Practice Guidelines, 116, 162 Precancerous, 143, 162 Precipitating Factors, 142, 162 Preclinical, 86, 162 Precursor, 124, 147, 149, 159, 162, 169 Predisposition, 15, 96, 162, 168 Prenatal, 15, 148, 151, 162, 163 Prenatal Diagnosis, 15, 163 Prevalence, 8, 22, 29, 36, 163 Prion, 16, 163 Probe, 9, 97, 163 Problem-Based Learning, 32, 163 Progression, 6, 19, 26, 36, 56, 138, 163 Promoter, 26, 163 Prone, 9, 163 Prostate, 11, 141, 163, 169

176 Human Genome Project

Protein C, 138, 139, 156, 163 Protein Conformation, 138, 163 Protein Isoforms, 138, 163 Protein Kinases, 160, 163 Protein S, 38, 103, 141, 145, 151, 163 Proteins, 5, 7, 24, 27, 36, 38, 138, 139, 141, 143, 144, 153, 158, 161, 162, 163, 166, 168, 169 Proto-Oncogenes, 160, 163 Proximal, 147, 163 Pruritic, 147, 163 Pruritus, 163, 165 Psychiatric, 19, 27, 59, 157, 163 Psychiatry, 6, 19, 30, 57, 66, 163, 164 Puberty, 29, 137, 164 Public Health, 19, 51, 57, 99, 116, 164 Public Policy, 13, 115, 164 Public Sector, 62, 164 Publishing, 39, 164 Puerperium, 160, 164 Pulmonary, 36, 141, 164, 169 Pulse, 9, 158, 164 P-value, 97, 164 Q Quality of Life, 49, 164 R Race, 13, 25, 102, 158, 164 Radiation, 150, 164, 165, 170 Radioactive, 141, 153, 156, 159, 164, 165 Randomized, 34, 148, 164 Receptor, 27, 139, 148, 152, 161, 164 Recombination, 20, 151, 164 Rectum, 139, 144, 155, 163, 164 Recurrence, 143, 164 Reductase, 139, 164 Refer, 1, 141, 144, 150, 156, 164 Refraction, 139, 165, 167 Regeneration, 38, 165 Regimen, 148, 165 Research Design, 27, 165 Respiration, 158, 165 Rheumatic Diseases, 17, 165 Rheumatism, 165 Rheumatoid, 17, 165 Rheumatoid arthritis, 17, 165 Risk factor, 34, 36, 100, 142, 165 Risk patient, 37, 165 Robotics, 23, 61, 165 S Scans, 5, 12, 96, 165 Schizophrenia, 28, 165 Scrapie, 16, 165

Screening, 4, 6, 7, 8, 10, 15, 25, 28, 29, 34, 36, 61, 62, 144, 151, 165 Secretion, 148, 165, 166 Segregation, 18, 143, 164, 165 Semen, 163, 166 Sensory loss, 8, 166 Sequence Analysis, 28, 166 Sequence Homology, 161, 166 Sequencer, 23, 166 Sequencing, 6, 7, 13, 15, 18, 23, 24, 25, 28, 35, 44, 51, 56, 73, 82, 97, 122, 123, 124, 162, 166 Serum, 36, 144, 156, 166 Sex Characteristics, 138, 164, 166 Side effect, 137, 166, 169 Signs and Symptoms, 4, 166 Skeletal, 8, 138, 148, 166 Skeleton, 155, 166 Skull, 148, 159, 166 Social Change, 105, 166 Social Environment, 164, 166 Social Work, 19, 20, 166 Soft tissue, 141, 166 Solid tumor, 36, 166 Somatic, 137, 148, 157, 158, 166 Specialist, 126, 167 Species, 140, 143, 145, 149, 153, 157, 158, 164, 166, 167, 169, 170 Spectrum, 15, 33, 167 Sperm, 138, 143, 167 Spina bifida, 159, 167 Spinal cord, 143, 159, 167, 168 Sporadic, 54, 167 Sprue, 110, 167 Sputum, 27, 167 Staging, 165, 167 Stem cell transplantation, 36, 167 Stem Cells, 167 Steroid, 139, 167 Stimulant, 147, 158, 167 Stimulus, 148, 167, 168 Strand, 28, 162, 167 Stress, 142, 162, 165, 167 Stridor, 28, 167 Stroke, 88, 114, 142, 167 Subacute, 154, 168 Subclinical, 154, 168 Support group, 20, 168 Sympathetic Nervous System, 159, 168 Sympathomimetic, 147, 148, 149, 159, 168 Symphysis, 163, 168 Systemic, 4, 17, 32, 141, 149, 154, 168

Index 177

Systemic disease, 4, 168 T Technology Transfer, 13, 101, 168 Temperament, 19, 168 Testicular, 139, 168 Thalamus, 141, 168 Therapeutics, 168 Thermal, 139, 140, 162, 168 Threonine, 161, 168 Threshold, 32, 97, 153, 168 Thrombosis, 163, 168 Toxic, iv, 152, 161, 168, 169 Toxicity, 148, 169 Toxicology, 48, 116, 169 Toxins, 139, 154, 169 Trachea, 141, 155, 167, 169 Tracheostomy, 28, 169 Transcription Factors, 160, 169 Transfection, 141, 169 Transgenes, 16, 169 Translating, 15, 40, 79, 100, 169 Translational, 6, 33, 36, 169 Transmitter, 147, 159, 169 Tuberculosis, 156, 169 Tumor marker, 141, 169

Tumor suppressor gene, 18, 26, 169 Tyrosine, 147, 169 U Unconscious, 138, 154, 169 Urethra, 163, 169 V Vascular, 154, 161, 169 Vasodilator, 148, 169 Vein, 159, 169 Venous, 163, 169 Ventricle, 154, 164, 168, 169 Venules, 141, 142, 170 Vesicular, 147, 170 Veterinary Medicine, 115, 170 Virus, 151, 152, 170 Vitro, 170 Vivo, 5, 170 W White blood cell, 139, 156, 157, 162, 170 X Xenograft, 138, 170 X-ray, 145, 150, 159, 165, 170 Y Yeasts, 150, 161, 170

178 Human Genome Project

Index 179

180 Human Genome Project

Human Genome Project - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Human Immunodeficiency Virus - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Human Papilloma Virus - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Influenza A - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Facial Paralysis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Wine - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Breast Augmentation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lipomas - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Barbiturates - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Cephalexin - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lymphedema - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Vaginitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Feet - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Glioblastoma Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Female Infertility - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Living Will - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Benzene - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Marburg Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Erythema Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Human Genome Project - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Human Immunodeficiency Virus - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Human Papilloma Virus - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Influenza A - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Facial Paralysis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Wine - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Breast Augmentation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lipomas - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Barbiturates - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Cephalexin - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lymphedema - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Vaginitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Feet - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Glioblastoma Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Female Infertility - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Living Will - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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