Theoretical Studies of Linkage Disequilibrium

连锁不平衡的理论研究

• 批准号: 7585695
• 负责人: HONGYU ZHAO
• 金额: $ 16.71万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7585695
• 关键词: Cataloging; Catalogs; Communities; Computing Methodologies; Data; Data Analyses; Development; Disease susceptibility; Frequencies; Genetic Markers; Genetic Population Study; Genetic Recombination; Genotype; Guidelines; Haplotypes; Human Genome; Individual; Knowledge; Lead; Linkage Disequilibrium; Methodology; Methods; Microsatellite Repeats; Natural Selections; Numbers; Pattern; Population; Population Genetics; Rate; Research Personnel; Single Nucleotide Polymorphism; Statistical Methods; Theoretical Studies; Variant; computer program; genotyping technology; interest; novel; tool; user-friendly

The long-term objective of this project is to develop statistical and computational methods for the analysis of haplotypes in population genetics. With the availability of large numbers of genetic markers in the human genome and the advances in genotyping technology, it is becoming feasible in population genetic studies to genotype thousands of markers in a large number of individuals from multiple populations. The analysis of such data poses challenging statistical and computational issues and both theoretical and empirical studies are needed to develop and evaluate statistical methods that can best extract the most relevant information for statistical inference of parameters of interest. The specific aims of this projects are: (1) Develop statistical and computational methods to infer haplotype frequencies from the observed unphased marker data in multiple populations; (2) Develop general guidelines for marker selection to identify disease susceptibility variants through haplotypes; (3) Use haplotypes consisting of single nucleotide polymorphisms as well as microsatellites from multiple populations for inference on population parameters as well as local recombination rates; (4) Investigate the power of statistical methods to identify chromosomal regions that have been subject to natural selections; (5) Implement and validate the developed methodologies in computer programs that will be distributed to the scientific community; and (6) Collaborate with other investigators to apply the methods and knowledge gained from this project to analyze data from other projects. Our methods will exploit two unique features in the data to be collected: the large number of populations around the world and the exhaustive cataloguing of haplotypes in extended chromosomal regions. The developments of these novel statistical methods and user-friendly computer programs will provide useful tools on population genetic studies and the analysis of data collected from other projects will lead to better understanding of relationships among various populations and different forces leading to linkage disequilibrium patterns in the human genome.

该项目的长期目的是开发统计和计算方法 人口遗传学中的单倍型分析。随着人类基因组中大量遗传标记的可用性以及基因分型技术的进步，在人群遗传研究中，它在基因型中越来越可行，可以在许多人群的大量个体中数千个标记。对此类数据的分析提出了具有挑战性的统计和计算问题，并且需要进行理论和经验研究来开发和评估统计方法，这些方法可以最好地提取最相关的信息来统计关注参数的统计推断。该项目的具体目的是： （1）开发统计和计算方法，以从多个人群中观察到的未基于的标记数据中推断出单倍型的频率； （2）制定标记物选择的一般指南，以通过单倍型鉴定疾病敏感性变体； （3）使用由单核苷酸多态性以及来自多个人群的微卫星组成的单倍型来推断人口参数以及局部重组率； （4）研究统计方法识别已自然选择的染色体区域的能力； （5）将在计算机程序中实施并验证将分发给科学界的开发方法； （6）合作 与其他研究人员一起运用从该项目中获得的方法和知识来分析其他项目的数据。我们的方法将利用要收集的数据中的两个独特功能：世界各地的大量人群以及扩展的染色体区域中单倍型的详尽编目。这些新型统计方法和用户友好的计算机程序的发展将为人群遗传研究提供有用的工具，从其他项目中收集的数据分析将使人们更好地理解各种人群之间的关系和不同的力量，从而导致人类基因组中的连锁不平衡模式。