Modeling DNA Diversity in Reverse Cholesterol Transport

描述(由申请人提供)： 组件3，C.Sing，Pi是这项题为建模反向胆固醇运输中的DNA多样性的合作研究项目拨款的组成部分，涉及另外两个组件：基于群体的基因组学和DNA基因分型(组件1，E.Boerwinkle，Pi)和群体遗传分析(组件2，A.Clark，Pi)。尽管出于实际和机构的目的，各个组成部分之间存在分工，但参与该项目的联合调查人员和顾问将作为一个团队合作，开发资源，以解决医学中最复杂和最具挑战性的问题之一，DNA序列变异与整个人群中人类健康的变异是如何关联的？ 组件3将开发模型并测试有关DNA序列变异(由组件I确定，并在普通人群样本中进行基因分型)与健康指标之间的关系的假设，使用反向胆固醇运输(RCT)作为基因组和普通人群心血管健康风险之间的中间生物学联系。为了实现这一目标，我们将利用组件2建立的关于种群结构和基因组组织的信息来：1)开发新的分析工具(组合划分、贝叶斯方法、神经网络等)。为了使用DNA序列变异预测心血管疾病风险的个体间差异，以及2)在62个候选基因中确定预测RCT测量个体间差异的可变DNA位点，这些候选基因在基于人群的样本中具有代表性，这些样本在基线和四个随访时间中分别代表2007名非洲裔美国人和2139名欧洲裔美国人。

DESCRIPTION (provided by applicant): Component 3, C. Sing, PI, is an integral part of this Collaborative Research Project grant entitled Modeling DNA Diversity in Reverse Cholesterol Transport involving two other components: population based genomics and DNA genotyping, (Component 1, E. Boerwinkle, PI) and population genetic analysis (Component 2, A. Clark, PI). Although there is a division of labor among components for practical and institutional purposes, the co-investigators and consultants engaged in this project will work as a team to develop resources to address one of the most complex and challenging problems in medicine, how is DNA sequence variation related to variation in human health in the population at large? Component 3 will develop models and test hypotheses about the relationship between DNA sequence variation (identified by Component I and genotyped in samples from the population at large) and variation in measures of health using reverse cholesterol transport (RCT) as the intermediate biological link between the genome and risk to cardiovascular health in the population at large. To accomplish this goal we will utilize information about population structure and genome organization established by Component 2 to: 1) develop new analytical tools (combinatorial partitioning, Bayesian methods, neural networks, etc.) for predicting interindividual variation in risk of cardiovascular disease using DNA sequence variation and 2) identify the variable DNA sites in 62 candidate genes that predict interindividual variation in measures of RCT in population-based samples that are representative of 2007 African-Americans and 2139 European-Americans at baseline and at each of four follow-up times.