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

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058239-05
Application #
6389667
Study Section
Special Emphasis Panel (ZHL1-CSR-R (M4))
Program Officer
Old, Susan E
Project Start
1997-08-15
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2003-06-30
Support Year
5
Fiscal Year
2001
Total Cost
$248,689
Indirect Cost
Name
Pennsylvania State University
Department
Social Sciences
Type
Schools of Arts and Sciences
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Weiss, Kenneth M; Lambert, Brian W (2011) When the time seems ripe: eugenics, the annals, and the subtle persistence of typological thinking. Ann Hum Genet 75:334-43
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
Weiss, Kenneth M; Buchanan, Anne V (2003) Evolution by phenotype: a biomedical perspective. Perspect Biol Med 46:159-82
Weiss, Kenneth M; Clark, Andrew G (2002) Linkage disequilibrium and the mapping of complex human traits. Trends Genet 18:19-24
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

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