THEORETICAL METHODS FOR STUDYING HAPLOTYPES

一个复杂的力量决定了之间的联系不平衡的程度 一组特定群体中的基因座。作为一般规则， 一对基因座之间的不平衡在每个基因座中系统地衰减， 由于重组而产生。然而，不平衡的数量在 人口的建立依赖于许多系统的和随机的 因素 在本提案中，我们专注于开发和应用方法来衡量 一组连锁基因座之间的关联程度。这些措施将 然后在被认为具有以下特征的染色体区域之间进行对比： 不同的物理距离/复合分数关系，以及 在不同组织学的人群中。这些方法将 基于线性回归和嵌套方差分析。我们打算 最初集中在不平衡的成对测量上。与对 在一组连锁基因座的所有对上考虑明智的措施， 非均衡估计是相关的，我们打算评估 这种相关性的影响。 我们开发的方法将使用模拟程序进行测试， 产生一组连锁标记基因座的群体单倍型数据。这些 我们还可以通过这些计划来评估各种 生物/人口力量，如标记基因座突变，基因流动， 和遗传漂变 最后，这些方法将应用于项目中收集的数据 第一、二、三章由基德、基德和沃德博士撰写。根据我们的经验 模拟研究，我们希望了解连锁不平衡 在这些项目中建立的关系。

A complex of forces determines the extent of linkage disequilibrium among a set of loci in a given population. As a general rule, the magnitude of disequilibrium between a pair of loci decays systematically in each generation due to recombination. However, the amount of disequilibrium at the founding of the population depends on numerous systematic and random factors. In this proposal, we focus on developing and applying methods to measure the degree of association among a set of linked loci. These measures will then be contrasted across chromosomal regions which are presumed to have different physical distance/recombination fraction relationship, as well as across populations with different histologies. These methods will be based on linear regression and nested analysis of variance. We intend to initially concentrate on pair wise measures of disequilibrium. With pair wise measures considered on all pairs of a set of linked loci, disequilibrium estimates are correlated, and we intend to evaluate the effect of this correlation. The methods that we develop will be tested using simulation programs that generate population haplotype data for a set of linked marker loci. These programs will also allow us to evaluate the effect of various biological/demographic forces, such as mutation at marker loci, gene flow, and genetic drift. Finally, these methods will be applied to the data collected in Projects 1, 2 and 3 by Drs. Kidd, Kidd and Ward. Given our experience from the simulation studies, we hope to understand the linkage disequilibrium relationships established in these projects.