GENETIC, EVOLUTIONARY, AND PHYLOGENETIC ANALYSIS OF HUMAN ALLELES

人类等位基因的遗传、进化和系统发育分析

• 批准号: 2463671
• 负责人: J C STEPHENS
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/2463671
• 关键词: alleles; animal genetic material tag; biochemical evolution; genetic mapping; genetic models; genetic polymorphism; human genetic material tag; linkage disequilibriums; major histocompatibility complex; mathematical model; model design /development; population genetics; statistics /biometry

We are trying to develop a functional understanding of gene sequence diversity for studied systems, notably major histocompatibility complex (MHC) loci, haplotypes, and alleles, microsatellite loci, and viral sequences. Our approach is to integrate population genetic, molecular evolution, and phylogenetic considerations with data on disease association and function. In order to do this, we are developing, improving, and applying algorithms for 1) detection and characterization of recombination and/or linkage disequilibrium among closely spaced loci; and 2) detection of genetic differentiation or identity. Currently, algorithms for detecting recombination among sequences or interpreting patterns of linkage disequilibrium are very crude and ad hoc, especially with regard to interpretation of such patterns. One of our goals is the quantitative identification of genetically alternative "motifs" among alleles at MHC and other loci. Ultimately, such data will be useful for testing putative disease associations. We are also exploring the potential for microsatellite applications in population and individual identification. We have developed statistical tests for microsatellite discrimination of divergent populations, population affiliation of a given genotype, and forensic testing of a DNA sample when appropriate population databases do not exist. We have applied these algorithms to existing data sets from tiger subspecies and domestic cats. The detection of genetic differentiation among tiger subspecies despite small sample sizes is a very good paradigm for detection of genetic differences (and potential disease associations) among highly characterized patient cohorts.

我们正试图发展对基因序列的功能性理解 研究系统的多样性，特别是主要组织相容性复合体 (MHC)基因座、单倍型和等位基因、微卫星基因座和病毒 序列的 我们的方法是整合群体遗传，分子 进化和系统发育方面的考虑， 联系和功能。 为了做到这一点，我们正在开发， 改进，并应用算法1）检测和 之间重组和/或连锁不平衡的表征 紧密间隔的基因座;和2）检测遗传分化或 身份 目前，用于检测重组之间的算法， 连锁不平衡的序列或解释模式非常 粗糙和特设的，特别是在解释这种 模式. 我们的目标之一是定量识别 在MHC和其他基因座的等位基因之间的遗传替代“基序”。 最终，这些数据将有助于测试假定的疾病 协会. 我们也在探索微卫星的潜力 在人口和个体识别中的应用。 我们有 开发了微卫星鉴别的统计测试， 不同的群体，给定基因型的群体从属关系，以及 法医检测DNA样本时，适当的人口数据库 并不存在 我们已经将这些算法应用于现有的数据集 老虎亚种和家猫的区别 基因检测 尽管样本量很小，但老虎亚种之间的差异 一个很好的检测遗传差异的范例（和 潜在的疾病关联） 同伙