POPULATION GENETICS OF HUMAN HYPERVARIABLE LOCI

人类高变基因座的群体遗传学

• 批准号: 3305327
• 负责人: Ranjan Deka
• 金额: $ 14.54万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3305327
• 关键词: ethnic group; gene frequency; genetic markers; genetic polymorphism; genome; human data; human population genetics; nucleic acid repetitive sequence; nucleic acid sequence; polymerase chain reaction; serology /serodiagnosis; southern blotting

The human genome contains a large number of hypervariable (HVR) sequences which often occur in short, tandemly repeated DNA segments. The copy number variation of such core sequences reveal genetic variation several orders larger than the classical serologic and biochemical genetic markers. While many such families of HVR loci are described in the human genome, their population genetic properties are relatively less well studied. The objective of this project is to rigorously study the population genetic characteristics of several such loci. Families of HVR loci consisting of di- tri- and tetra-nucleotide simple sequence repeats and chi-like core sequences will be studied for population variation. Blood samples from randomly chosen individuals belonging to several diverse ethnically well-defined human populations of the old and the new world will be studied by Southern blot and PCR techniques. Data gathered will consist of the number, size distribution, and frequencies of alleles at these loci characterized by different repeat unit lengths. Such data will be used to postulate theoretical models to describe the origin and maintenance of HVR polymorphism in human populations. Furthermore, since the populations to be studied in this project are also the ones examined by traditional serologic and biochemical markers, it will be possible to contrast intra- as well as inter-population variation of HVR loci with those at classical markers. Theoretical work of this project will enable us to examine the effect of known selection regime (at the globin gene regions) on HVR polymorphisms adjacent to these gene regions. Development of new statistical methods for studying polymorphisms with multiple alleles will lead to rigorous attempts to examine the generality and reasons underlying the reported departures from Hardy-Weinberg and linkage equilibrium at the HVR loci and to relate the functional attributes of HVR loci with the multi-model allele size distributions at such loci. Understanding of the population genetic characteristics of hypervariable loci is essential for re-affirming the utility of such polymorphisms for human microdifferentiation studies and for utilizing such loci in gene mapping and forensic identification purposes.

人类基因组包含大量的高变（HVR）序列 通常出现在短的串联重复的DNA片段中。 复制 这些核心序列的数量变化揭示了遗传变异， 数量级大于经典的血清学和生化遗传标记。 虽然在人类基因组中描述了许多这样的HVR基因座家族， 它们的种群遗传特性研究得相对较少。 的 该项目的目的是严格研究群体遗传学， 几个这样的基因座的特征。 HVR基因座家族，包括 二、三和四核苷酸简单重复序列和类chi核心 将研究序列的群体变异。 的血液样本 随机选择的个体属于几个不同的种族 将研究旧世界和新世界的明确人口 Southern杂交和PCR技术。 收集的数据将包括 这些位点上等位基因的数量、大小分布和频率 其特征在于不同的重复单元长度。 这些数据将用于 假设理论模型来描述HVR的起源和维持 人类群体中的多态性。 此外，由于人口 在这个项目中研究的也是传统的检查 血清学和生化标志物，这将是可能的对比内， 以及HVR基因座与经典HVR基因座的群体间变异， 标记。 这个项目的理论工作将使我们能够审查 已知选择方案（在珠蛋白基因区域）对HVR的影响 与这些基因区域相邻的多态性。 开发新 研究具有多个等位基因的多态性的统计方法将 导致严格的尝试，以检查的普遍性和原因， 报告偏离哈代-温伯格和连锁平衡， HVR基因座，并将HVR基因座的功能属性与 多模型等位基因大小分布在这样的基因座。 理解 高变基因座的群体遗传特征对于 再次肯定这种多态性对人类的效用， 微分化研究和在基因作图中利用这些基因座 和法医鉴定目的。