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 #
5R01HL058240-04
Application #
6184188
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
$578,057
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Genetics
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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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
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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
Nelson, M R; Kardia, S L; Ferrell, R E et al. (2001) A combinatorial partitioning method to identify multilocus genotypic partitions that predict quantitative trait variation. Genome Res 11:458-70
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

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