Abstract

Project 1 is a research component of a Cooperative Research Program involving two other research components, Project 2, Weiss, PI and Project 3, Sing, PI. One of the most complex and challenging problems in human biology and medicine is defining the relationship between DNA sequence variation and interindividual variation in quantitative risk factors for complex diseases having a multifactorial etiology. As their knowledge about the basic human DNA sequence increases, so will their need to define the range of natural variation n human populations and to explore the relationship between nucleotide diversity and phenotype variation in measures of human health. The goal of Project 1 is to identify and measure DNA sequence variation in 13 genes that play a central role in key physiological functions involved in the development of cardiovascular disease (CVD), i.e. genes involved in lipid metabolism. Project 1 will apply state-of-the-art automated fluorescence-based sequencing and high-throughput DNA genotyping methods to uncover and assess DNA sequence variation in three human populations: non-Hispanic Whites from Rochester, MN (low CVD risk), African-Americans from Jackson, MS (intermediate CVD risk) and non-Hispanic Whites from North Karelia, Finland (high CVD risk). These studies will provide an unprecedented

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058238-04
Application #
6184399
Study Section
Special Emphasis Panel (ZHL1-CSR-R (M4))
Project Start
1997-08-15
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
4
Fiscal Year
2000
Total Cost
$719,971
Indirect Cost

  Institution

Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Stengard, J H; Frikke-Schmidt, R; Tybjaerg-Hansen, A et al. (2007) Variation in 5'promoter region of the APOE gene contributes to predicting ischemic heart disease (IHD) in the population at large: the Copenhagen City Heart Study. Ann Hum Genet 71:762-71
Stengard, Jari H; Kardia, Sharon L R; Hamon, Sara C et al. (2006) Contribution of regulatory and structural variations in APOE to predicting dyslipidemia. J Lipid Res 47:318-28
Fullerton, Stephanie M; Buchanan, Anne V; Sonpar, Vibhor A et al. (2004) The effects of scale: variation in the APOA1/C3/A4/A5 gene cluster. Hum Genet 115:36-56
Hamon, S C; Stengard, J H; Clark, A G et al. (2004) Evidence for non-additive influence of single nucleotide polymorphisms within the apolipoprotein E gene. Ann Hum Genet 68:521-35
Fullerton, Stephanie M; Clark, Andrew G; Weiss, Kenneth M et al. (2002) Sequence polymorphism at the human apolipoprotein AII gene ( APOA2): unexpected deficit of variation in an African-American sample. Hum Genet 111:75-87
Stengard, Jari H; Clark, Andrew G; Weiss, Kenneth M et al. (2002) Contributions of 18 additional DNA sequence variations in the gene encoding apolipoprotein E to explaining variation in quantitative measures of lipid metabolism. Am J Hum Genet 71:501-17
Templeton, A R; Clark, A G; Weiss, K M et al. (2000) Recombinational and mutational hotspots within the human lipoprotein lipase gene. Am J Hum Genet 66:69-83
Fullerton, S M; Clark, A G; Weiss, K M et al. (2000) Apolipoprotein E variation at the sequence haplotype level: implications for the origin and maintenance of a major human polymorphism. Am J Hum Genet 67:881-900
Nickerson, D A; Taylor, S L; Fullerton, S M et al. (2000) Sequence diversity and large-scale typing of SNPs in the human apolipoprotein E gene. Genome Res 10:1532-45
Templeton, A R; Weiss, K M; Nickerson, D A et al. (2000) Cladistic structure within the human Lipoprotein lipase gene and its implications for phenotypic association studies. Genetics 156:1259-75

Showing the most recent 10 out of 13 publications