POPULATION MIXTURES EFFECTS ON GENETIC VARIATION

这项建议的总体目标是区分和区分 遗传连锁效应和过去效应对群体混合的影响 人口结构的变化，以便可以考虑到这种影响 基因作图、研究进化史和法医鉴定的目的 遗传学。利用聚合和扩散模型的理论，我们 建议制定一种统一的连锁不平衡(LD)测量方法， 与标记的重组距离保持单调关系 对于重复基因座和单核苷酸多态(SNPs)。这个 过去人口规模的人口变化对多点的影响 LD将被研究通过一般的逐步进化的重复基因座 突变过程(允许不对称)。我们也将发展 检验等位基因大小限制的影响的方法 扩张/收缩突变偏倚对推断的后果 遗传连锁与种群混合。这将允许 由多点Ld产生的区别的表征 种群混合与遗传连锁。此外，新的实验室 选定混合种群的聚合酶链式反应DNA多态数据 (非洲裔美国人，美国西班牙裔，来自新莱昂的墨西哥人，以及混血儿 乌拉圭东北部的乌拉圭人)将生成精确的 用新开发的方法估计这些人群中的混合物质 人群特异性标记，并评估性别特异性的影响 利用线粒体分析亲本群体的差异基因流 和Y染色体单倍型。这样的数据，除了模型之外 定向交配的效果，将为相关的 混合群体可用于遗传连锁的参数 学习。该项目的结果将有助于(A)评估 不同混交史种群在发展中的效用 使用重复标记定位基因的策略，以及(B)在 了解复合体基因突变的历史 疾病。

The overall goal of this proposal is to characterize and differentiate the effects of population mixtures from that of genetic linkage and past demographic changes, so that such effects can be taken into account for purposes of gene mapping, studying evolutionary history, and forensic genetics. Using the theory of coalescence and diffusion models, we propose to develop a unified measure of linkage disequilibrium (LD) that maintains a monotone relationship with recombination distance of markers for repeat loci as well as single nucleotide polymorphisms (SNPs). The effects of past demographic changes of population size on multi-point LD will be studied for repeat loci that evolve via a general stepwise mutation process (with asymmetry allowed). We shall also develop methods for examining the effect of allele size constraints and expansion/contraction mutation bias on inference of the consequences of genetic linkage versus mixture of populations. This will allow a characterization of the distinction between multi-point LD generated by population mixture versus genetic linkage. In addition, new laboratory data on PCR-based DNA polymorphisms on selected mixed populations (African-Americans, US Hispanics, Mexicans from Nuevo Leon, and admixed Uruguayans of northeastern Uruguay) will be generated to obtain precise estimates of admixture in these populations by using newly developed population-specific markers, and to evaluate the effects of sex-specific differential gene flow from parental populations by using mitochondrial and Y-chromosome haplotypes. Such data, in addition to the models of the effects of directional mating, will set precise bounds for relevant parameters under which mixed populations can be used for genetic linkage studies. The results of this project will aid (a) in assessing the utility of populations of different mixture history in developing strategies for mapping genes using repeat markers, and (b) in understanding the history of mutations at genes underlying complex diseases.