Integrating SNPs and STRPs in Population Genetics

将 SNP 和 STRP 整合到群体遗传学中

• 批准号: 7906032
• 负责人: Bret A Payseur
• 金额: $ 28.52万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7906032
• 关键词: Address; Biology; Complex; Computer Simulation; Development; Disease; Event; Evolution; Foundations; Genetic Polymorphism; Genetic Variation; Genome; Genomics; Goals; Human; Human Genome; Inherited; Joints; Link; Linkage Disequilibrium; Maps; Measures; Modeling; Mutate; Mutation; Outcome; Pattern; Performance; Population; Population Genetics; Process; Property; Recording of previous events; Research; Short Tandem Repeat Polymorphism; Single Nucleotide Polymorphism; Statistical Methods; Theoretical Studies; Variant; base; human DNA; human disease; improved; insight; interest; molecular marker; trait

DESCRIPTION (provided by applicant): Patterns of variation at molecular markers provide exciting insights into the evolution of natural populations. Variation at the two most commonly used molecular markers, single nucleotide polymorphisms (SNPs) and short tandem repeat polymorphisms (STRPs), arises from different mutational processes, leading to complementary inferences about evolutionary forces. Because of higher mutation rates, STRPs better reveal recent evolutionary events, whereas slowly mutating SNPs are more powerfully applied to reconstructing older evolutionary events. Despite this crucial difference, patterns of polymorphism at SNPs and STRPs have rarely been compared directly in empirical or theoretical studies. The proposed research will address this important challenge by jointly examining genomic patterns of variation at SNPs and STRPs in human populations and by conducting computer simulations that explicitly model the contrasting mutational processes at the two marker classes. Specifically, this project will (1) compare expected patterns of polymorphism at SNPs, STRPs, and SNPs+STRPs generated under different evolutionary processes, (2) compare the performance of SNPs, STRPs, and SNPs+STRPs as markers for association studies of complex traits, (3) characterize expected linkage disequilibrium and other diversity correlations between linked SNPs and STRPs, and (4) measure patterns of co-variation between linked SNPs and STRPs across the human genome. This combined empirical and theoretical effort will yield the first systematic comparison of patterns of SNP and STRP polymorphism. Evolutionary scenarios that produce patterns of polymorphism that are relatively robust to variation in the STRP mutational model will be specifically sought as promising avenues for inference. Important outcomes of the proposed research include: objective guidance on marker choice based on timescale and evolutionary process of interest, a framework for integrating polymorphism at neighboring SNPs and STRPs throughout the human genome, and a foundation for the development of statistical methods that combine these two markers to enhance population genetic inference. By directly examining linkage disequilibrium between SNPs and STRPs across the human genome and quantitatively comparing the power of analyses using different or combined marker types, this research will also yield improved strategies for association mapping of complex human diseases. This project will examine the properties of different classes of human DNA variation. The results will help reveal the causes of the genetic variation that underlies complex inherited diseases. Project Relevance: This project will examine the properties of different classes of human DNA variation. The results will help reveal the causes of the genetic variation that underlies complex inherited diseases.

描述（由申请人提供）：分子标记的变异模式为自然种群的进化提供了令人兴奋的见解。两种最常用的分子标记，即单核苷酸多态性 (SNP) 和短串联重复多态性 (STRP) 的变异源自不同的突变过程，从而得出关于进化力的互补推论。由于突变率较高，STRP 可以更好地揭示最近的进化事件，而缓慢突变的 SNP 则更有力地应用于重建较早的进化事件。尽管存在这一重要差异，但 SNP 和 STRP 的多态性模式很少在实证或理论研究中进行直接比较。拟议的研究将通过联合检查人群中 SNP 和 STRP 的基因组变异模式，并通过进行计算机模拟来明确模拟两个标记类别的对比突变过程，来应对这一重要挑战。具体来说，该项目将 (1) 比较不同进化过程下产生的 SNP、STRP 和 SNP+STRP 的预期多态性模式，(2) 比较 SNP、STRP 和 SNP+STRP 作为复杂性状关联研究标记的性能，(3) 表征连锁 SNP 和 STRP 之间的预期连锁不平衡和其他多样性相关性，以及 (4) 测量之间的共变模式 将人类基因组中的 SNP 和 STRP 连接起来。这种经验和理论相结合的努力将首次对 SNP 和 STRP 多态性模式进行系统比较。产生对 STRP 突变模型的变化相对稳健的多态性模式的进化场景将被特别寻求作为有希望的推理途径。拟议研究的重要成果包括：根据感兴趣的时间尺度和进化过程对标记选择提供客观指导，在整个人类基因组中整合邻近 SNP 和 STRP 多态性的框架，以及开发结合这两种标记以增强群体遗传推断的统计方法的基础。通过直接检查人类基因组中 SNP 和 STRP 之间的连锁不平衡，并定量比较使用不同或组合标记类型的分析能力，这项研究还将产生复杂人类疾病关联图谱的改进策略。该项目将研究不同类别的人类 DNA 变异的特性。这些结果将有助于揭示复杂遗传性疾病背后的遗传变异的原因。 项目相关性：该项目将检查不同类别的人类 DNA 变异的特性。这些结果将有助于揭示复杂遗传性疾病背后的遗传变异的原因。