SNP Discovery

Program Description

The NIEHS Environmental Genome Project is a multidisciplinary, collaborative effort focused on examining the relationships between environmental exposures, inter-individual sequence variation in human genes and disease risk in U.S. populations. As a cornerstone of the EGP, NIEHS contracted with the University of Washington to sequence a panel of human samples in order to identify SNPs (single nucleotide polymorphisms) in over 600 environmentally responsive genes. The NIEHS has focused on studying the biological significance of the genetic variants in DNA repair, cell cycle control, drug metabolizing enzymes, apoptosis, and differentiation, and signal transduction mechanisms responsible for the regulation of other classes of genes. All this information is available in the GeneSNPs database created for the NIEHS EGP by the University of Utah. Ultimately, the project will provide dense genetic maps of human genes that can be used to evaluate the interplay of genetic variation and environmental exposures on human disease risk. Understanding these interactions will contribute to the understanding of human diseases resulting from exposure to environmental agents.

Program Contact Elizabeth A. Maull, Ph.D. maull@niehs.nih.gov

Contractor - SNP Discovery Deborah A. Nickerson, Ph.D. University of Washington Identification of Single Nucleotide Polymorphisms (SNPs) in Disease Susceptibility Genes debnick@u.washington.edu Grantee/Center Website: http://egp.gs.washington.edu/

Select Program Highlights - SNP Discovery

The University of Washington NIEHS SNPs (http://egp.gs.washington.edu/) has sequenced over 607 environmentally responsive genes in a panel of 95 human DNA samples since 2001. They have sequenced in excess of 14 MB of baseline genome sequence, resulting in 85,547 SNPs. Summary statistics (http://egp.gs.washington.edu/summary_data.html) .

NIEHS, through the efforts at the University of Washington, has been the fifth major producer of genotypes in found in dbSNPs (Zaitlen et al. (Genome Research 15(11):1594-600, 2005),

A subset of genes sequenced has previously been reported in:

• Livingston RJ, Von Niederhausern A, Jegga AG, Crawford DC, Carlson CS, Rieder MJ, Gowrisankar S, Aronow BJ, Weiss RB, Nickerson DA (2004) Pattern of sequence variation across 213 environmental response genes, Genome Res 14: 1821-31.