Modeling DNA Diversity in Reverse Cholesterol Transport

描述（由申请人提供）： 构成部分3，C. Sing，PI，是这个合作研究项目的一个组成部分，该项目名为“反向胆固醇转运中的DNA多样性建模”，涉及其他两个组成部分：基于人口的基因组学和DNA基因分型（组件1，E。Boerwinkle，PI）和群体遗传分析（组分2，A. Clark，PI）.尽管出于实际和机构目的，各组成部分之间存在劳动分工，但参与该项目的共同研究者和顾问将作为一个团队开发资源，以解决医学中最复杂和最具挑战性的问题之一，即DNA序列变异如何与人类健康变异相关？ 组件3将开发关于DNA序列变异（由组件I鉴定，并在来自广大人群的样本中进行基因分型）与健康指标变异之间关系的模型和检验假设，使用胆固醇逆向转运（RCT）作为基因组与广大人群心血管健康风险之间的中间生物联系。为了实现这一目标，我们将利用组件2建立的有关群体结构和基因组组织的信息：1）开发新的分析工具（组合划分，贝叶斯方法，神经网络等）。用于使用DNA序列变异预测心血管疾病风险的个体间变异，以及2）鉴定62个候选基因中的可变DNA位点，所述候选基因预测基于人群的样本中RCT测量的个体间变异，所述样本在基线和四个随访时间的每一个时代表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.