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
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