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Understanding Our Genetic Inheritance

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Understanding Our Genetic Inheritance Available from the Nat ional Technical Information Service, U.S. Department of Commerce, Springfield, Virginia 22161 Price: Printed copy A05 Microfiche A01 Codes are used for pricing all publications. The code is determined by the number of pages in publication. Information pertaining to the pricing codes can be found in current issues of the following publications, which are generally available in most libraries: Energy Research Abstracts (ERA)_- Government Reports Announcements and Index (GRA and I); Scientific and Technical Abstract Reports (STAR)_- and pGblication, NTIS-PR-360 available from NTIS at the above address. Cover: Schematic representation of selected human chromosomes, the cellular structures that contain genes. Human cells contain 23 pairs of chromosomes. Alternating dark and light bands, the result of chemical staining, arc used as visible landmarks for locating genes. Lines to the right of each chromo­ some mark positions where genetic markers have been mapped. DOE/ER-0452P Understanding Our Genetic Inheritance • The U.S. Human Genome Project: The First Five Years FY 1991-1995 U.S. DEPARTMENT OF HEALTH U.S. DEPARTMENT OF ENERGY AND HUMAN SERVICES Office of Energy Research Public Health Service Office of Health and National Institutes of Health Environmental Research National Center for Human Human Genome Program Genome Research NIH Publication No. 90-1590 April 1990 i ;/ Table of Contents Executive Summary . vu Introduction . ~ . 1 Program Goals 5 Scientific Goals • • • • • • • • • • • • • • • •I • • • • • • • • • • • • • • • • • • • 9 1. Mapping and Sequencing the Human Genome . 9 Genetic Map . 10 Physical Map . 11 DNA Sequencing . 14 2. Model Organisms . 17 3. Informatics: Data Collection and Analysis 18 4. Ethical, Legal, and Social Considerations 20 5. Research Training 22 6. Technology Development 23 7. Technology Transfer . 24 Implementation 27 Administration of Research . 27 Management Systems . 27 Role of Research Centers . 27 Construction . 29 Workshops and Meetings . 29 Role of NIH and DOE . 30 National Institutes of Health . 30 U.S. Department of Energy . .. 31 Memorandum of Understanding . 31 iii I il JV Role of Other Federal Agencies . 34 National Science Foundation . 34 U.S. Department of Agriculture . 34 Howard Hughes Medical Institute . 35 International Collaboration . 35 Budget 37 Appendix 1: U.S. Department of Energy Health And Environmental Research Advisory Committee . 41 Appendix 2: National Institutes of Heal ~h Program Advisory Committee on the Human Genome . 43 Appendix 3: Joint DOE-NIH Subcommittee on the Human Genome . 45 Appendix 4: Memorandum of Understanding Between the U.S. Department of Energy and the National Institutes of Health . 47 Appendix 5: Additional Participants in the Development of the Five-Year Plan 51 Appendix 6: Joint Informatics Task Force Proposal . 53 Appendix 7: Report of the Working Group on Ethical, Legal, and Social Issues Related to Mapping and Sequencing the Human Genome . 65 Appendix 8: Joint Mapping Working Group 75 Appendix 9: Joint Informatics Task Force . 77 Appendix 10: Joint Working Group on Ethical, Legal, and Social Issues . 79 Appendix 11: Scientific Goals of the U.S. Human Genome Project . 81 Glossary 85 v VI Understanding Our Genetic Inheritance The U.S. Human Genome Project: I ;{ The First Five Years FY 1991-1995 Executive Summary The Human Genome Initiative is a worldwide research effort with the goal of analyzing the structure of humari DNA and determining the location of the estimated 100,000 human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the functioning of the human genome. The information generated by the human genome project is expected to be the source book for biomedical science in the 21st century and will be of immense benefit to the field of medicine. It will help us to understand and eventually treat many of the more than 4000 genetic diseases that afflict mankind, as well as the many multifactorial diseases in which genetic predisposition plays an important role. A centrally coordinated project focussed on specific objectives is believed to be the most efficient and least expensive way of obtaining this information. In the course of the project much new technology will be developed to facilitate a broad range of biological and biomedical research, bring down the cost of many experiments, and find application in numerous other fields. The basic data produced will be collected Vll m electronic databases that will make the information readily accessible m convenient form to all who need it. This report describes the plans for the U.S. human genome project and updates those originally prepared by the Office of Technology Assessment (OTA) and the National Research Council (NRC) in 1988. In the intervening two years, improvements in technology for almost every aspect of genomics research have taken place. As a result, more specific goals can now be set for the project. Five-year goals have been identified for the following areas, which together encompass the human genome project: o Mapping and Sequencing the Human Genome o Mapping and Sequencing the Genomes of Model Organisms o Data Collection and Distribution o Ethical, Legal, and Social Considerations o Research Training o Technology Development o Technology Transfer This plan sets out specific scientific goals to be achieved in the first five years together with the rationale for each goal. The specific goals will be reviewed annually and updated as further advances in the underlying technology occur. The plan presented here was prepared jointly by the National Institutes of Health (NIH) and the Department of Energy (DOE), the two agencies that have received funding earmarked for the human genome project. Over the past two years, these agencies have developed a highly synergistic and well-integrated approach to carrying out this initiative, as evidenced by the adoption of this common plan. The National Institutes of Health has a natural interest in the Human Genome Initiative in view of its long history of supporting research in genetics and molecular biology as an integral part of its mission to improve the health of all Americans. The Department of Energy has a long-standing program of genetic research directed at improving the ability to assess the effects of radiation and energy~related chemicals on human health. viii To achieve the scientific goals set out in this report, a number of administrative measures have been put in place. In addition, a newsletter, an electronic bulletin board, a comprehensive administrative database, and other communications tools are being set up to facilitate communication and tracking of progress. Research centers will be established to promote the collaboration of investigators from diverse disciplines on a major task of the genome program. DOE has already established three large centers in its National Laboratories and NIH will establish 10 to 20 additional centers over the next five years. The centers will become foci for collaboration with investigators at other locations and with industrial organizations that want to develop applications of the research results, thereby creating networks of interrelated projects. Meetings and workshops will be organized to bring together investigators with common research objectives and to encourage collaboration, exchange of materials and use of common starting materials or protocols wherever these are appropriate. It is expected that mapping and sequencing groups will coalesce around individual human chromosomes or around particular model organisms. NIH and DOE will continue their synergistic working relationship and will also interact closely with other interested agencies, as well as with genome mapping programs in other countries as they get organized. Close ties with industry and with the medical community have been established, and will continue to be encouraged, to ensure efficient technology transfer. The private sector is involved in this project at all levels from participation in the advisory committees to receipt of grants and contracts. The overall budget needs for the effort are still anticipated to be the same as those identified by the OTA and the NRC, namely about $200 million per year for approximately 15 years. Fiscal years 1988 to 1990 have been a period for getting organized and getting research under way. The five-year goals specified in this plan are for the period FY 1991 through FY 1995 and assume the program will rapidly reach the level of funding specified above. ix X The First Five Years FY 1991-1995 Introduction The Human Genome Initiative is a worldwide research effort that has the goal of analyzing the structure of human DNA and determining the location of all human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the functioning of the human genome. The information generated by the human genome project is expected to be the source book for biomedical science in the 21st century. It will have a profound impact on and expedite progress in a variety of biological fields, including those such as developmental biology and neurobiology, where scientists are just beginning to understand the underlying molecular mechanisms. The analysis and interpretation of the information will occupy scientists for many years to come. Thus, the maximal benefit of the human
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