Mapping and Sequencing the Human Genome (1988) / Chapter Skim
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1. Executive Summary
1. Executive Summary
Pages 1-11
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As more of our genes are mapped and their DNA sequenced, we will have an increasingly useful resource an essential data base that will facilitate research in biochemistry, physiology, cell biology, and medicine. This data base will have a major impact on health care and disease prevention as well as on our understanding of cells and organisms.
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· Important early goals of the effort should be to acquire a highresolution genetic linkage map of the human genome, a collection of ordered DNA clones, and a series of complementary physical maps of increasing resolution. The ultimate goal would be to obtain the complete nucleotide sequence of the human genome, starting from the materials in the ordered DNA clone collection.
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The Scientific Advisory Board, composed primarily of expert scientists knowledgeable in relevant fields, would provide advice not only on peer review, but also on quality control, international cooperation, coordination of efforts of the laboratories in the project, and the operations of the stock and data centers. An outline of the major issues presented in this report follows, with genome mapping, genome sequencing, the handling of information and materials, and strategies for implementation and management of a human genome project discussed in turn.
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1. Nucleo1Ides, four diNerenl ~_~~^~_~_l~ _c u~ .
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Physical maps are derived mainly from chemical measurements made on the DNA molecules that form the human genome. These maps can be of several different types and include restriction maps and ordered DNA clone collections, as well as lower resolution maps of expressed genes or anonymous (function unknown)
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Advanced technology, such as the handling of larger DNA molecules and the development of new cloning vectors for them, will expedite the preparation of such clone collections. Thus, much of the effort in the next few years should be devoted to refining existing mapping techniques and developing even more powerful new ones.' The committee believes that most support should go to groups that are attempting to map large genomes, with support for different mapping methods proceeding in parallel.
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nucleotides must be ordered; simply to print out such a DNA sequence would require nearly a million pages in a book like this. To obtain this critical resource in a timely fashion a special effort must be mounted, but, because of the high cost arid slow rate of DNA sequencing with current technology, sequencing of the entire genome should not be initiated at present.
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The facility might also be involved in the routine conversion of large human DNA fragments, cloned as artificial chromosomes, into more readily accessible bacterial virus or cosmic DNA clone collections. It may also need to fingerprint all the DNA clones by a single method to provide a standard indexing procedure.
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A human genome project of this type need not threaten the existing biological research community for several reasons. First, the money ought not be provided at the expense of currently funded biological research.
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In multidisciplinary centers, 3 to 10 research groups, each with an outstanding independent scientific director anal a different but related focus, are envisioned as sharing equipment and personnel in core facilities and collaborating to accomplish a larger goal than any single group could readily achieve on its own. These centers could efficiently coordinate the large number of different experimental and computer capabilities needed for the development of techniques as well as work out optimal strategies that produce actual mapping and sequencing data.
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· To suggest mechanisms for strict quality controls on the sequence and mapping data collected. · To promote international cooperation, serving as a liaison to projects outside the United States regardless of their funding sources.
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