The Human Genome Project is an ambitious research effort aimed at deciphering the chemical makeup of the entire human genetic code (i.e., the genome). The primary work of the project is to develop three research tools that will allow scientists to identify genes involved in both rare and common diseases. Another project priority is to examine the ethical, legal, and social implications of new genetic technologies and to educate the public about these issues. Although it has been in existence for less than 6 years, the Human Genome Project already has produced results that are permeating basic biological research and clinical medicine. For example, researchers have successfully mapped the mouse genome, and work is well under way to develop a genetic map of the rat, a useful model for studying complex disorders such as hypertension, diabetes, and alcoholism. KEY WORDS: genome, genetic mapping; DNA; applied research; molecular genetics
The Human Genome Project is an international research project whose primary mission is to decipher the chemical sequence of the complete human genetic material (i.e., the entire genome), identify all 50,000 to 100,000 genes contained within the genome, and provide research tools to analyze all this genetic information. This ambitious project is based on the fact that the isolation and analysis of the genetic material contained in the DNA(1) (figure 1)(Figure 1 omitted) can provide scientists with powerful new approaches to understanding the development of diseases and to creating new strategies for their prevention and treatment. Nearly all human medical conditions, except physical injuries, are related to changes (i.e., mutations) in the structure and function of DNA. These disorders include the 4,000 or so heritable "Mendelian" diseases that result from mutations in a single gene; complex and common disorders that arise from heritable alterations in multiple genes; and disorders, such as many cancers, that result from DNA mutations acquired during a person's lifetime. (For more information on the genetics of alcoholism, see the articles by Goate, pp. 217-220, and Grisel and Crabbe, pp. 220-227.)
Although scientists have performed many of these tasks and experiments for decades, the Human Genome Project is unique and remarkable for the enormity of its effort. The human genome contains 3 billion DNA building blocks (i.e., nucleotides), enough to fill approximately one thousand 1,000-page telephone books if each nucleotide is represented by one letter. Given the size of the human genome, researchers must develop new methods for DNA analysis that can process large amounts of information quickly, cost-effectively, and accurately. These techniques will characterize DNA for family studies of disease, create genomic maps, determine the nucleotide sequence of genes and other large DNA fragments, identify genes, and enable extensive computer manipulations of genetic data.
Focus OF THE HUMAN GENOME PROJECT
The primary work of the Human Genome Project has been to produce three main research tools that will allow investigators to identify genes involved in normal biology as well as in both rare and common diseases. These tools are known as positional cloning (Collins 1992). These advanced techniques enable researchers to search for disease-linked genes directly in the genome without first having to identify the gene's protein product or function. (See the article by Goate, pp. 217-220.)(Article omitted) Since 1986, when researchers first found the gene for chronic granulomatous disease(2) through positional cloning, this technique has led to the isolation of considerably more than 40 disease-linked genes and will allow the identification of many more genes in the future (table 1).(Table 1 omitted)
Each of the three tools being developed by the Human Genome Project helps bring the specific gene being sought into better focus (see sidebar, pp. 192-193).(Sidebar omitted) The first of these tools, the genetic map, consists of thousands of landmarks--short, distinctive pieces of DNA--more or less evenly spaced along the chromosomes. …