POPULATION GENETICS OF HUMAN HYPERVARIABLE LOCI

人类高变基因座的群体遗传学

• 批准号: 3305326
• 负责人: Ranjan Deka
• 金额: $ 16.09万
• 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/3305326
• 关键词: ethnic group; gene frequency; genetic markers; genetic polymorphism; genome; human population genetics; nucleic acid repetitive 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高变（HVR）序列 通常出现在短的、串联重复的 DNA 片段中。 副本 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。 虽然人类基因组中描述了许多此类 HVR 基因座家族， 他们的群体遗传特性研究相对较少。 这 该项目的目标是严格研究群体遗传 几个这样的位点的特征。 HVR 基因座家族包括 双、三和四核苷酸简单序列重复和类卡核心 将研究序列的群体变异。 血液样本来自 随机选择属于几个不同种族的个体 将研究新旧世界明确的人口 通过Southern印迹和PCR技术。 收集的数据将包括 这些位点等位基因的数量、大小分布和频率 其特点是重复单元长度不同。 此类数据将用于 假设理论模型来描述 HVR 的起源和维护 人类群体的多态性。 此外，由于人们 本项目所研究的内容也是传统方法所研究的内容 血清学和生化标记物，将有可能对比内部 以及 HVR 位点与经典位点的群体间变异 标记。 该项目的理论工作将使我们能够检验 已知选择机制（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 研究多个等位基因多态性的统计方法将 导致严格尝试检查普遍性和背后的原因 报告的 Hardy-Weinberg 偏离和连锁平衡 HVR 位点并将 HVR 位点的功能属性与 这些位点的多模型等位基因大小分布。 的理解 高变位点的群体遗传特征对于 重申此类多态性对人类的效用 微分化研究以及在基因作图中利用此类位点 和法医鉴定目的。