MODELING DNA DIVERSITY IN CARDIOVASCULAR HEALTH/DISEASE

说明(摘自申请者摘要)项目1是一项研究 合作研究计划的组成部分，涉及另外两项研究 组件，项目2，Weiss，PI和项目3，Sing，PI。 人类生物学中最复杂和最具挑战性的问题之一 医学正在定义DNA序列变异和 复杂疾病定量危险因素的个体间差异 具有多因素病因的。因为他们对人类的基本知识 DNA序列增加了，所以他们需要定义天然的范围 人类种群的变异与探索二者的关系 人类健康指标中的核苷酸多样性和表型变异。 项目1的目标是识别和测量DNA序列变异 13个在关键生理功能中发挥核心作用的基因 心血管疾病(CVD)的发展，即参与 脂类代谢。项目1将应用最先进的自动化 基于荧光测序和高通量DNA基因分型方法 在三个人类群体中发现并评估DNA序列变异： 来自明尼苏达州罗切斯特(低心血管风险)的非西班牙裔白人，非裔美国人 来自杰克逊，MS(中度心血管疾病风险)和来自北方的非西班牙裔白人 芬兰卡雷利亚(心血管疾病风险高)。这些研究将提供一个 前无古人

DESCRIPTION (adapted from the applicants 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