Rutgers Scientists Mapping DNA Links To Complex Diseases

When completed by the end of this year, the linkage map will be published and made available free of charge to the biomedical community, according to its sponsor, the SNP Consortium. The nonprofit consortium is a collaboration of the pharmaceutical industry, several leading academic centers, a major medical research charity and other firms.

Rutgers' Laboratory of Computational Genetics in the department of genetics will analyze data provided by the consortium to create a map of the interaction among some 2,000 single nucleotide polymorphisms or SNPs. SNPs are variations in DNA that are shared by many people, says laboratory director and research professor of computational genetics Tara C. Matise.

SNPs provide a shortcut for pinpointing certain genes that may contribute to disease, says Matise, because they are easy to locate and easy to use as markers to track genes that may have an impact on genetic expression. Many SNPs lie within genes associated with a disease, while others are near such genes, she adds.

Through the work of the SNP Consortium and the sequenced map of the human genome produced earlier this year, the locations of these SNPs are known, says Matise. "But we don't have any understanding of how much they interact or recombine. And that's a key factor in tracking dysfunctional genes that may contribute to disease," Matise notes.

Such knowledge is expected to help medical researchers pinpoint the genetic differences that make one person more susceptible to a disease than another, as well as less able to benefit from therapy, the scientist says. "Understanding SNP interactions will lead to greater knowledge of disease processes, and safer, more effective therapies and medications," Matise says.

The research will be especially useful for complex diseases like heart disease, diabetes, high blood pressure, schizophrenia, bipolar disorder, alcoholism and osteoporosis, which involve many faulty genes as opposed to just one, as in cystic fibrosis and sickle cell anemia. SNPs are key agents of change among the roughly 3 billion nucleotide base pairs -- the building blocks of DNA and genes -- that make up the human genome. While 99.9 percent of the genome is identical for everyone, SNPs are among the .01 percent that account for all the racial and other physiological differences among humans.

"Nucleotides code for proteins that give people different traits, such as blue eyes instead of brown, athletic ability or artistic ability," Matise says, "traits that also include how susceptible an individual may be to certain diseases."

SNPs are valuable research tools because they are the most common and simple type of genetic variation shared among people, she adds. "They occur roughly every 1,000 base pairs along the human genome. As such, they are easy to detect and serve as genetic landmarks to help researchers navigate the genome in search of particular genes."

The SNP linkage map is being developed using one of two high performance, E-10000 Sun Microsystems computers, each with 64 processors, that are located at Rutgers Center for Advanced Information Processing (CAIP). CAIP is jointly supported by Rutgers, the New Jersey Commission on Science and Technology, and major computer and telecommunications industry firms. Rutgers has the largest 10000 configuration of any university in the United States.

The linkage map is another step toward the consortium's goal of constructing a high-density, high-quality map of SNPs throughout the human genome. The group has so far identified and mapped more than 1.5 million SNPs distributed throughout the genome.

Consortium members include the Wellcome Trust, Astra Zeneca, Aventis Pharma, Bayer AG, Bristol-Myers Squibb Company, F. Hoffman La Roche, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer Inc., Searle (now a part of Pharmacia), Motorola Inc., IBM and Amersham Pharmacia Biotech.

Other members are the Whitehead Institute for Biomedical Research, Washington University School of Medicine in St. Louis, the Wellcome Trust's Sanger Centre, Stanford Human Genome Center and Cold Spring Harbor Laboratory. Orchid BioSciences performs third-party validation and quality control for the project.