Mapping and Sequencing the Human Genome -- Copyright -- Preface -- Contents -- MAPPING AND SEQUENCING THE HUMAN GENOME -- 1 Executive Summary -- GENOME MAPPING -- GENOME SEQUENCING -- INFORMATION AND MATERIALS HANDLING -- IMPLEMENTATION STRATEGIES -- MANAGEMENT STRATEGY -- 2 Introduction -- GENOMES, GENES, AND GENOMIC MAPS -- Genomes Consist of DNA Molecules That Contain Many Genes -- The Human Genome Is Composed of 24 Different Types of DNA Molecules -- The Human Genome Can Be Mapped in Many Different Ways -- MEDICAL IMPLICATIONS OF DETAILED HUMAN GENOME MAPS -- IMPLICATIONS FOR BASIC BIOLOGY -- EXPECTED GECHNOLOGICAL DEVELOPMENTS GENERATED BY A HUMAN GENOME PROJECT AND THEIR IMPACT ON BIOLOGICAL RESEARCH -- IMPACT ON THE RESEARCH BY SMALL GROUPS -- REFERENCES -- 3 Implications for Medicine and Science -- MEDICAL USES -- A Map of the Human Genome Will Greatly Facilitate the Identification of Specific Disease Genes -- Disease Genes Promise to Provide Important Insights into Human Biology -- Specific Medical Applications -- Toward an Understanding of Cancer -- IMPLICATIONS FOR BASIC BIOLOGY -- What Aspects of Genome Organization Are Important for Genome Function? -- Many New Human Genes and Proteins Will Be Identified -- How Do Organisms Evolve? -- References -- 4 Mapping -- Early Cytological Mapping Efforts Depended on Examining Chromosomes Under the Light Microscope -- The Current Revolution in Genome Mapping Is Based on the Use of Recombinant-DNA Techniques -- FUNDAMENTALS OF GENOME MAPPING -- Physical Maps Describe Chromosomal DNA Molecules, Whereas Genetic Linkage Maps Describe Patterns of Inheritance -- The Development of Ordered Collections of DNA Clones Is an Important -- Both Physical and Genetic Linkage Maps Can Be Constructed with Various Degrees of Resolution and Connectivity -- GENETIC LINKAGE MAPPING.

Restriction Fragment Length Polymorphisms Are Convenient Landmarks for Genetic Linkage Mapping -- Genetic Linkage Mapping Requires the Study of Many People in Large Family Groups -- RFLPs Are Useful for Interrelating Physical and Genetic Linkage Maps -- A Reference RFLP Map for the Human Would Be a Critical Tool for Studying Inherited Diseases -- MAKING PHYSICAL MAPS -- Medium-Resolution Mapping of Restriction Sites Is Facilitated by New Methods of Preparing and Separating Large DNA Molecules -- High-Resolution Mapping of Restriction Sites Will Require the Use of Ordered Collections of DNA Clones -- Fingerprinting Methods Can Be Used to Order DNA Clones -- The Optimal Method for Preparing Ordered Collections of DNA Clones Is Not Yet Clear -- IMMEDIATE APPLICATIONS OF CHROMOSOME MAPS -- CONCLUSIONS AND RECOMMENDATIONS -- Recent Breakthroughs Have Set the Stage for Large-Scale Mapping -- Different Mapping Methods Should Proceed in Parallel -- The Improvement of Physical Mapping Techniques Should Be Closely Coupled to Actual Attempts to Map Large Genomes -- Specific Improvements That Will Facilitate Map Construction and Usefulness Can Be Identified -- REFERENCES -- 5 Sequencing -- WHY SEQUENCE THE ENTIRE HUMAN GENOME? -- CURRENT TECHNOLOGY IN DNA SEQUENCING: CHEMICAL AND ENZYMATIC METHODS -- THE DIFFICULTY OF DETERMINING THE SEQUENCE OF THE HUMAN GENOME WITH CURRENT TECHNOLOGY -- THE ACCURACY OF DNA SEQUENCING -- EMERGING AND FUTURE TECHNOLOGY -- OPTIONS AND RECOMMENDATIONS -- The Project Should Begin with Two Kinds of Studies -- To Derive the Full Benefit of the Human Genome Sequence Will Require Many New Tools, Including a Comprehensive Database… -- DNA Sequence Determinations Require Quality Control -- REFERENCES -- 6 The Collection, Analysis, and Distribution of Information and Materials -- PRESENT INFORMATION-HANDLING ORGANIZATIONS -- GenBank/EMBL.

Mendelian Inheritance in Man -- Human Gene Mapping Library -- Centre d'Etude du Polymorphisme Humain -- MAPPING DATA BASES REQUIRED FOR A HUMAN GENOME PROJECT -- The Collaborative Facilities Needed To Generate an RFLP Map Must Be Expanded -- All Human Map Data Should Be Accessible from a Single Data Base -- A Material Collection and Distribution Facility for Ordered Sets of Cloned DNA Fragments Will Be an Important First Stage in… -- A DNA SEQUENCE DATA BANK DEDICATED TO A HUMAN GENOME PROJECT -- A Concerted Initiative Aimed at Determining the Sequence of the Human Genome Will Generate Large Amounts of DNA Sequence Data -- All Data Must Be Entered Electronically or Magnetically -- An Initial Analysis Should Be Performed by a Central Facility -- An Example of an Initial Sequence Analysis -- Establishing an Efficient Computer Network -- The Need for Research on Data Analysis -- The Estimated Cost -- CONCLUSIONS -- REFERENCES -- 7 Implementation and Management Strategies -- FUNDING A HUMAN GENOME PROJECT -- Projects with the Potential to Make Substantial Technological Improvements in Genome Analysis Should Receive Top Priority -- Both Small Research Laboratories and Larger Multidisciplinary Centers Should Be Encouraged -- The Establishment of a Single Large Production Center is Not Advisable at Present -- Decisions for Funding Should Be Made by Peer Review -- The Human Genome Project Requires New and Distinctive Funding of About 200 Million per Year -- Mapping Efforts Should Be Accelerated and Coordinated -- The Sequencing Effort Should Evolve and Grow with Time -- International Collaboration on the Project Is Desirable -- MANAGING A HUMAN GENOME PROJECT -- Three Possible Organizational Plans -- Organizational Plan A: A Lead Agency and a Scientific Advisory Board -- Organizational Plan B: An Interagency Committee and Scientific Advisory Board.

Organizational Plan C: Interagency Committee, Administrative Agency, and Scientific Advisory Board -- REFERENCE -- 8 Implications for Society -- COMMERCIAL AND LEGAL IMPLICATIONS -- ETHICAL AND SOCIAL IMPLICATIONS -- Conducting a Genome Mapping and Sequencing Project -- Interpreting the Medical Implications of Genetic Information -- The Use and Abuse of a Complete Genome Map -- REFERENCES -- Appendix A Glossary -- Appendix B Curricula Vitae of Committee Members -- Appendix C Invited Speakers at Committee Meetings -- Index.