POPULATION MIXTURES EFFECTS ON GENETIC VARIATION

种群混合对遗传变异的影响

• 批准号: 6555836
• 负责人: Ranajit Chakraborty
• 金额: $ 19.47万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6555836
• 关键词: African American; Hispanic Americans; Mexican Americans; South American; biochemical evolution; computer assisted sequence analysis; computer program /software; forensic medicine; gene expression; gene frequency; gene mutation; genetic markers; genetic models; genetic polymorphism; human data; human population genetics; human population study; linkage disequilibriums; linkage mapping; mathematical model; model design /development; nucleic acid sequence; polymerase chain reaction; restriction fragment length polymorphism; sex differentiation; tissue /cell culture

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.

本提案的总体目标是， 从遗传连锁和过去的影响，人口混合的影响 人口结构的变化，这样的影响可以考虑到， 基因定位、研究进化史和法医学的目的 遗传学 利用聚结和扩散模型理论， 建议制定一个统一的连锁不平衡（LD）措施， 与标记的重组距离保持单调关系 重复基因座以及单核苷酸多态性（SNP）。的 人口规模的过去人口变化对多点 LD将研究重复基因座，通过一般的逐步进化， 突变过程（允许不对称）。 我们还将开发 检测等位基因大小限制的影响的方法， 扩展/收缩突变偏倚对推断 遗传连锁与种群混合。 这将允许 表征多点LD之间的区别， 种群混合与遗传连锁 此外，新实验室 所选混合人群中基于PCR的DNA多态性数据 （非裔美国人、美国拉美裔人、来自新莱昂的墨西哥人，以及 乌拉圭东北部的乌拉圭人）将生成，以获得精确的 估计混合在这些人群中使用新开发的 群体特异性标记，并评估性别特异性 利用线粒体技术研究亲本群体的差异基因流 和Y染色体单倍型。 这些数据，除了 定向交配的影响，将为相关的 混合群体可用于遗传连锁的参数 问题研究 该项目的结果将有助于（a）评估 不同混合历史群体在发展中的效用 使用重复标记定位基因的策略，和（B）在 了解复杂基因突变的历史 疾病