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Single nucleotide polymorphisms (SNPs) are DNA sequence variations that occur when a single nucleotide (A,T,C,or G) in the genome sequence is altered. For example a SNP might change the DNA sequence AAGGCTAA to ATGGCTAA. Two of every three SNPs involve the replacement of cytosine (C) with thymine (T). SNPs occur every 100 to 300 bases along the 3-billion-base human genome. SNPs can occur in both coding (gene) and noncoding regions of the genome. Many SNPs have no effect on cell function, but scientists believe others could predispose people to disease or influence their response to a drug. Although more than 99% of human DNA sequences are the same across the population, variations in DNA sequence can have a major impact on how humans respond to disease; environmental insults such as bacteria, viruses, toxins, and chemicals; and drugs and other therapies. This makes SNPs of great value for biomedical research and for developing pharmaceutical products or medical diagnostics. SNPs are also evolutionarily stable --not changing much from generation to generation --making them easier to follow in population studies. Scientists believe SNP maps will help them identify the multiple genes associated with such complex diseases as cancer, diabetes, vascular disease, and some forms of mental illness. These associations are difficult to establish with conventional gene-hunting methods because a single altered gene may make only a small contribution to the disease. Several groups worked to find SNPs and ultimately create SNP maps of the human genome. Among these groups were the U.S. Human Genome Project (HGP) and a large group of pharmaceutical companies called the SNP Consortium or TSC project. The likelihood of duplication among the groups was small because of the estimated 3 million SNPs, and the potential payoff was high. In addition to the pharmacogenomic, diagnostic, and biomedical research implications, SNP maps are helping to identify thousands of additional markers along the genome, thus simplifying navigation of the much larger genome map generated by researchers in the HGP. Human Genome Project SNP Mapping GoalsIn 1998, as part of their last five-year plan, the DOE and NIH Human Genome Programs established goals to identify and map SNPs. These goals were as follows:
What is the SNP consortium (TSC)?In April 1999, ten large pharmaceutical companies and the U.K. Wellcome Trust philanthropy announced the establishment of a consortium headed by Arthur L. Holden to find and map 300,000 common SNPs. The goal was to generate a widely accepted, high-quality, extensive, publicly available map using SNPs as markers evenly distributed throughout the human genome. In the end, many more SNPs (1.8 million total) were discovered than planned originally. Now that the SNP discovery phase of the TSC project is essentially complete, the emphasis has shifted to studying SNPs in populations. Various TSC member laboratories are genotyping a subset of SNPs as part of the Allele Frequency Project. The goal of the TSC allele frequency/genotype project is to determine the frequency of certain SNPs in three major world populations. Who are members of the SNP consortium?The international member companies, which together committed at least $30 million, are APBiotech, AstraZeneca Group PLC, Aventis, Bayer Group AG, Bristol-Myers Squibb Co., F. Hoffmann-La Roche, Glaxo Wellcome PLC, IBM, Motorola, Novartis AG, Pfizer Inc., Searle, and SmithKline Beecham PLC. The Wellcome Trust contributed at least $14 million. Laboratories funded by these companies to identify SNPs are located at the Whitehead Institute, Sanger Centre, Washington University (St. Louis), and Stanford University. Data management and analysis take place at Cold Spring Harbor Laboratory. See Consortium Updates:
Why should private companies fund a publicly accessible genome map?The SNP consortium views its map as a way to make available an important, precompetitive, high-quality research tool that will spark innovative work throughout the research and industrial communities. The map will be a powerful research tool to enhance the understanding of disease processes and facilitate the discovery and development of safer and more effective medications. Whose DNA was analyzed to create the consortium's SNP map?The SNP consortium used DNA resources from a pool of samples obtained from 24 individuals representing several racial groups. This is a subset of the DNA reference panel for SNP identification collected by the NIH National Human Genome Research Institute. The anonymous, voluntary DNA contributions were made with informed consent specifically for this use. Are SNP data available to the public?SNP data were made available through a consortium Web site at quarterly intervals during the project's first year and at monthly intervals during the second year. SNPs also were deposited in the public dbSNP database. This cycle of releases ceased fall 2001 once the discovery phase was finished, but with the recent additions of genotype and allele frequency data, a new data dump took place in the fall of 2002. For more on human ploymorphisms, see HGVBASE (Human Genome Variation Database) - a human gene-based polymorphism database. More InformationArticles:
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