Genomic Approaches to Common Chronic Disease

描述（由申请人提供）：该基因组卓越中心 科学（CEGS）涉及四个组成部分：DNA重测序（组成部分1， 希克森），基于群体的基因分型（组分2，Boerwinkle），进化 和人口历史研究（组成部分3，克拉克）， 可变DNA位点，预测代谢和 一般人口健康的生理措施（组成部分4， Sing）。虽然这些组件之间存在劳动分工， 共同调查员和顾问的作用 参与该项目的人员将作为一个团队开发工具和方法， 解决医学中最复杂和最具挑战性的问题之一， DNA序列变异与人群健康状况的关系 逍遥法外 该环境和全球服务中心四个组成项目的补充活动将： 1)建立61条19号染色体DNA序列变异数据库 参与关键代谢过程的基因， 常见疾病，如心血管疾病和糖尿病（AIM 1），2）发展 研究工具和方法，用于将这种遗传变异与 个体间的变化在健康的措施（目的2）和3）应用这些 预测健康的代谢和生理措施的战略， 非洲裔美国人和非西班牙裔欧洲裔美国人人群（AIM 3）。 组件1将对来自两个人中的每个人的20个个体的61个基因进行重新测序。 一只黑猩猩和一只狒狒组件2将对所有变量进行基因分型 在2007年基于人口的样本中由组分I鉴定的DNA位点 来自CARDIA的非裔美国人和2139名非西班牙裔欧洲裔美国人 study.组成部分3将开发进化群体遗传学方法， 鉴定用于基因型-表型研究的位点子集。 第4部分将建立DNA序列之间关系的模型， 变异（由组分1鉴定，并在来自 按构成部分2分列的一般人口的健康状况和 人口众多。组成部分4还将管理CEGS上的公共资源 网站建设，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.