Genomic Approaches to Common Chronic Disease

描述(申请者提供)：这个基因组学卓越中心 科学(CEGS)涉及四个组成部分：DNA重新测序(组成部分1， Hixson)，基于群体的基因分型(成分2，Boerwinkle)，进化 和人口历史研究(构成部分3，克拉克)和确定 预测代谢和代谢的个体间差异的可变DNA位点 一般人群健康的生理测量(组成部分4， 唱)。尽管这些组件之间存在分工，但 实际和体制目的、联合调查员和咨询人 参与这个项目将作为一个团队工作，开发工具和方法，以 解决医学中最复杂和最具挑战性的问题之一，如何 DNA序列变异与人群健康变异的关系 逍遥法外？ 专家小组四个组成部分项目的补充活动将： 1)建立61号染色体19号染色体的完整DNA序列变异数据库 参与导致糖尿病风险的关键代谢过程的基因 常见疾病，如心血管疾病和糖尿病(目标1)，2)发展 研究工具和方法将这种遗传变异与 健康指标的个体间差异(目标2和3)适用于这些 预测健康的代谢和生理指标的策略 非洲裔美国人和非西班牙裔欧洲裔美国人(目标3)。 组件1将对这两个个体中的20个个体中的61个基因进行重新排序 种群，一只黑猩猩和一只浣熊。组件2将对所有变量进行基因分型 2007年以人口为基础的样本中成分I确定的DNA位点 来自CARDIA的非洲裔美国人和2139名非西班牙裔欧洲裔美国人 学习。组件3将开发进化种群遗传方法 确定用于基因-表型研究的位点的子集。 组件4将开发DNA序列之间关系的模型 变异(由成分1鉴定，并在来自 按构成部分2分列的总体人口)和健康衡量标准的差异 广大的人口。组件4还将管理CEGS上的公共资源 网站并提供行政支持。

DESCRIPTION (provided by applicant): This Center of Excellence in Genomic Science (CEGS) involves four components: DNA resequencing (Component 1, Hixson), population-based genotyping (Component 2, Boerwinkle), evolutionary and population history studies (Component 3, Clark) and identification of variable DNA sites that predict interindividual variation in metabolic and physiological measures of health in the population at large (Component 4, Sing). Although there is a division of labor among these components for practical and institutional purposes, the co-investigators and consultants engaged in this project will work as a team to develop tools and methods 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? The complementary activities of the four component projects of this CEGS will: 1) establish a complete DNA sequence variation database on 61 chromosome 19 genes that are involved in key metabolic processes that contribute to risk of common diseases such as cardiovascular disease and diabetes (AIM 1), 2) develop research tools and methods for relating this genetic variation to interindividual variation in measures of health (AIM 2) and 3) apply these strategies for predicting metabolic and physiological measures of health in African-American and non-Hispanic European-American populations (AIM 3). Component 1 will resequence the 61 genes in 20 individuals from each of the two populations, a Chimpanzee and a Baboon. Component 2 will genotype all variable DNA sites identified by Component I in a population-based sample of 2007 African-Americans and 2139 non-Hispanic European- Americans from the CARDIA study. Component 3 will develop evolutionary-population genetic methods for identifying subsets of sites to be used in genotype-phenotype studies. Component 4 will develop models for the relationship between DNA sequence variation (identified by Component 1 and genotyped in samples from the population at large by Component 2) and variation in measures of health in the population at large. Component 4 will also manage public resources on a CEGS web site and provide administrative support.