POPULATION MIXTURES EFFECTS ON GENETIC VARIATION

在过去的四年里，我们的研究表明， 亚群大多数人类基因调查的主要组成部分 人口。差异地影响各种遗传变异的测量。 识别混合物的存在并鉴别混合物 件.因此，对于理解 遗传变异和重建进化历史。我们 证明种群混合的效果更有效 通过使用被称为 可变数目串联重复（VNTR）基因座。由于这些新的变化 基因座的产生不同于经典标记中的新变异 （血型和蛋白质）。需要新的分析工具来研究 进化动力学和统计特性的总结措施 这些高变基因座的遗传变异。 VNTR位点 （微型卫星。短串联重复序列和小型卫星）似乎是 由不同的突变机制维持。这将是 我们提出的研究。 使用这两种类型的人口混合（合并和基因流），我们 建议制定研究群体内的方法， 种群间变异等来研究进化的相关性 个体之间和群体之间的差异。多地点措施还将 可以用于DNA进化研究 指纹数据不同突变分子机制的模型 （涉及股内和股间工艺）。的 等位基因鉴定不完全和趋同变化的影响 （独立突变产生相同拷贝数的重复单位， VNTR基因座）。所使用的技术将是分析性的 随机过程的工具（包括漂移和突变）， 计算机模拟不同历史人群的数据 的混合物。以及其他物种的数据。将用于验证 理论新的实验数据将用于设计模拟 程序和参数。 这些研究也将帮助我们了解 不同混合人群中复杂疾病的病因 历史并为绘制这些疾病基因的图谱制定调查策略 使用高变基因座。

During the past four years our research has demonstrated that mixtures of subpopulations. the main constituent of most genetic surveys of human populations. differentially affect various measures of genetic variation. Recognizing the presence of mixtures and identifying the mixture components. therefore. are important for understanding the maintenance of genetic variation and for reconstructing evolutionary history. We demonstrated that the effects of population mixture are more efficiently detected through the use of the class of polymorphic loci known as variable number of tandem repeat (VNTR) loci. Since new variation at these loci is generated differently from new variation in classical markers (blood groups and proteins). new analytical tools are needed to study the evolutionary dynamics and statistical properties of summary measures of genetic variation at these hypervariable loci. VNTR loci (microsatellites. short tandem repeats. and minisatellites) appear to be maintained by different mutational mechanisms. which will be the focus of our proposed studies. Using both types of population mixtures (amalgamation and gene flow), we propose to develop methods for studying intrapopulation and interpopulation variation and so to investigate evolutionary relatedness between individuals and between populations. Multilocus measures will also be developed that can be used for evolutionary studies using DNA fingerprint data. Models of different molecular mechanisms of mutations (involving intrastrand and interstrand processes) will be used. The effects of incomplete identification of alleles and of convergent changes (independent mutations producing the same copy-number of repeat units at a VNTR locus) will be examined. The techniques used will be analytical tools of stochastic processes (incorporating drift and mutations) and computer simulations. Data on human populations with different histories of mixtures. as well as data from other species. will be used to validate the theory. New experimental data will be used to design the simulation procedures and parameters. Such studies will also help us to understand the etiology of complex diseases in populations with different mixture histories. and to develop survey strategies for mapping such disease genes using hypervariable loci.