POPULATION GENETICS OF HUMAN HYPERVARIABLE LOCI

人类基因组包含大量的高变数(HVR)序列 它们通常出现在短的、重复的DNA片段中。复制品 这些核心序列的数量变异揭示了几个遗传变异 比经典的血清学和生化遗传标记更大的目的。 虽然人类基因组中描述了许多这样的HVR基因座家族， 对它们的群体遗传特性的研究相对较少。这个 本项目的目标是严格研究群体遗传学。 几个这样的基因座的特征。由以下组成的HVR基因座家族 二-三、四核苷酸简单序列重复序列和类CHI核心 将对序列进行种群变异研究。血液样本来自 随机选择的属于几个不同种族的人 将研究新旧世界中定义明确的人口。 通过Southern印迹和聚合酶链式反应技术。收集的数据将包括 这些基因座上等位基因的数量、大小分布和频率 以不同的重复单位长度为特征的。这些数据将被用来 描述暖通空调起源和维护的假设理论模型 人类群体的多态现象。此外，由于人口增加到 在这个项目中被研究的也是由传统的 血清学和生化标志物，将有可能进行体内对比。 以及人类免疫缺陷病毒基因座的种群间变异。 记号笔。这个项目的理论工作将使我们能够研究 已知选择机制(珠蛋白基因区域)对HVR的影响 这些基因区域附近的多态现象。新技术的发展 研究具有多个等位基因的多态的统计方法将 导致了严格的尝试来检查一般性和潜在的原因 报告的偏离Hardy-Weinberg和连锁平衡的 并将HVR基因座的功能属性与 这些基因座的多模式等位基因大小分布。对这一概念的理解 高变位基因座的群体遗传特征对 重新肯定这种多态对人类的效用 微分化研究及其在基因定位中的应用 以及法医鉴定目的。

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.