Mapping and Sequencing the Human Genome (1988) / Chapter Skim
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2. Introduction
2. Introduction
Pages 12-25
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Unprecedented advances in molecular and cellular biology, in biochemistry, in genetics, and in structural biology-occurring at an accelerating rate over the past decade define this as a unique and opportune moment in our history: For the first time we can envision obtaining easy access to the complete sequence of the 3 billion nucleotides in human DNA and deciphering much of the information contained therein. Converging developments in recombinant DNA technology and genetics make obtaining a complete ordered DNA clone collection indexed to the human genetic linkage map a realistic immediate goal.
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In this way, many previously unknown human genes and proteins will become available for biochemical, physiological, and medical studies. The knowledge gained will have a major impact on health care and disease prevention; it will also raise challenging issues regarding rational, wise, and ethical uses of science and technology.
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14 C, E ~ in ~ C)
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For the information in the coding sequences of a gene to be expressed, the DNA of a gene must first be transcribed into an RNA molecule (Figure 2-31. Before the RNA strand leaves the cell's nucleus, the intron sequences are cut out of this RNA strand by a process called RNA splicing, thereby bringing the exon sequences into contiguity.
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17 DNA is a double helix: Each nucleotide on a strand of DNA has a complementary nucleotide on the other strand. The information on one DNA strand is therefore redundant to that on the other (that is because of complementary base pairing (Figure 2-2A)
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The RNA quickly undergoes a reaction called RNA splicing that removes all of its intron sequences and joins together its coding sequences (its exons)
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Such information is said to constitute a gene or genome map. Since there are 24 different DNA molecules in the human genome, a complete human gene map consists of 24 maps, each in the linear form of the DNA molecule itself.
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DNA lacking a specific restriction site yields a larger restriction fragment when cut by the enzyme than DNA containing the site; hence, the designation restriction fragment length polymorphism (REDIP)
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. The sequence of only one of the two DNA strands is given since the other one has a precisely complementary sequence The sequence should be read from left to right in sueeessive lines down the page.
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for basic biology. This is especially true because we expect a human genome project to support mapping and sequencing investigations that are carried out concurrently in other extensively studied organisms, including the Escherichia cold bacterium, the lower eucaryote Saccharomyces cerevisiae (a yeasts, the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, the mouse Mus musculus, and possibly also a plant such as maize or Arabidopsis.
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These and other implications for basic biology are discussed in greater detail in Chapter 3. EXPECTED TECHNOLOGICAL DEVELOPMENTS GENERATED BY A HUMAN GENOME PROJECT AND THEIR IMPACT ON BIOLOGICAL RESEARCH The process of mapping and sequencing the human genome is likely to have important spin-offs in the form of new technologies with broad applicability in both basic and applied biological research.
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In the committee's view, however, a mapping and sequencing project should have as its primary goal an increase in the power and range of the research potential of small groups of indivicluals. The complete nucleotide sequences of the genomes of the several organisms of major experimental interest will provide a critical reference data base for interpreting and studying the many human genes that will be discovered.
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Recombinant DNA: A Short Course.
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