Genomic Approaches to Common Chronic Disease

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DESCRIPTION (provided by applicant): This Center of Excellence in Genomic Science (CEGS) involves four components: DNA resequencing (Component 1, Hixson), population-based genotyping (Component 2, Boerwinkle), evolutionary and population history studies (Component 3, Clark) and identification of variable DNA sites that predict interindividual variation in metabolic and physiological measures of health in the population at large (Component 4, Sing). Although there is a division of labor among these components for practical and institutional purposes, the co-investigators and consultants engaged in this project will work as a team to develop tools and methods to address one of the most complex and challenging problems in medicine, how is DNA sequence variation related to variation in human health in the population at large? The complementary activities of the four component projects of this CEGS will: 1) establish a complete DNA sequence variation database on 61 chromosome 19 genes that are involved in key metabolic processes that contribute to risk of common diseases such as cardiovascular disease and diabetes (AIM 1), 2) develop research tools and methods for relating this genetic variation to interindividual variation in measures of health (AIM 2) and 3) apply these strategies for predicting metabolic and physiological measures of health in African-American and non-Hispanic European-American populations (AIM 3). Component 1 will resequence the 61 genes in 20 individuals from each of the two populations, a Chimpanzee and a Baboon. Component 2 will genotype all variable DNA sites identified by Component I in a population-based sample of 2007 African-Americans and 2139 non-Hispanic European- Americans from the CARDIA study. Component 3 will develop evolutionary-population genetic methods for identifying subsets of sites to be used in genotype-phenotype studies. Component 4 will develop models for the relationship between DNA sequence variation (identified by Component 1 and genotyped in samples from the population at large by Component 2) and variation in measures of health in the population at large. Component 4 will also manage public resources on a CEGS web site and provide administrative support.