Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM065509-04
Application #
6790582
Study Section
Ethical, Legal, Social Implications Review Committee (GNOM)
Program Officer
Eckstrand, Irene A
Project Start
2001-09-03
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
4
Fiscal Year
2004
Total Cost
$2,518,610
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Genetics
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Tiosano, Dov; Audi, Laura; Climer, Sharlee et al. (2016) Latitudinal Clines of the Human Vitamin D Receptor and Skin Color Genes. G3 (Bethesda) 6:1251-66
Climer, Sharlee; Templeton, Alan R; Zhang, Weixiong (2015) Human gephyrin is encompassed within giant functional noncoding yin-yang sequences. Nat Commun 6:6534
Rahbar, Mohammad H; Samms-Vaughan, Maureen; Dickerson, Aisha S et al. (2015) Blood lead concentrations in Jamaican children with and without autism spectrum disorder. Int J Environ Res Public Health 12:83-105
Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne; Dyson, Greg et al. (2015) Subgroups at high risk for ischaemic heart disease:identification and validation in 67?000 individuals from the general population. Int J Epidemiol 44:117-28
Dyson, Greg; Sing, Charles F (2014) Efficient identification of context dependent subgroups of risk from genome-wide association studies. Stat Appl Genet Mol Biol 13:217-26
Jian, Xueqiu; Boerwinkle, Eric; Liu, Xiaoming (2014) In silico tools for splicing defect prediction: a survey from the viewpoint of end users. Genet Med 16:497-503
Lusk, Christine M; Dyson, Greg; Clark, Andrew G et al. (2014) Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region: the Atherosclerosis Risk in Communities study. Hum Genet 133:1105-16
Climer, Sharlee; Templeton, Alan R; Zhang, Weixiong (2014) Allele-specific network reveals combinatorial interaction that transcends small effects in psoriasis GWAS. PLoS Comput Biol 10:e1003766
Jian, Xueqiu; Boerwinkle, Eric; Liu, Xiaoming (2014) In silico prediction of splice-altering single nucleotide variants in the human genome. Nucleic Acids Res 42:13534-44
Gazave, Elodie; Ma, Li; Chang, Diana et al. (2014) Neutral genomic regions refine models of recent rapid human population growth. Proc Natl Acad Sci U S A 111:757-62

Showing the most recent 10 out of 76 publications