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自然种群中多态性标记位点与影响复杂二分性状的位点之间的连锁不平衡建模。

Modeling linkage disequilibrium between a polymorphic marker locus and a locus affecting complex dichotomous traits in natural populations.

作者信息

Luo Z W, Wu C I

机构信息

School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, England.

出版信息

Genetics. 2001 Aug;158(4):1785-800. doi: 10.1093/genetics/158.4.1785.

Abstract

Linkage disequilibrium is an important topic in evolutionary and population genetics. An issue yet to be settled is the theory required to extend the linkage disequilibrium analysis to complex traits. In this study, we present theoretical analysis and methods for detecting or estimating linkage disequilibrium (LD) between a polymorphic marker locus and any one of the loci affecting a complex dichotomous trait on the basis of samples randomly or selectively collected from natural populations. Statistical properties of these methods were investigated and their powers were compared analytically or by use of Monte Carlo simulations. The results show that the disequilibrium may be detected with a power of 80% by using phenotypic records and marker genotype when both the trait and marker variants are common (30%) and the LD is relatively high (40-100% of the theoretical maximum). The maximum-likelihood approach provides accurate estimates of the model parameters as well as detection of linkage disequilibrium. The likelihood method is preferred for its higher power and reliability in parameter estimation. The approaches developed in this article are also compared to those for analyzing a continuously distributed quantitative trait. It is shown that a larger sample size is required for the dichotomous trait model to obtain the same level of power in detecting linkage disequilibrium as the continuous trait analysis. Potential use of these estimates in mapping the trait locus is also discussed.

摘要

连锁不平衡是进化遗传学和群体遗传学中的一个重要课题。一个尚未解决的问题是将连锁不平衡分析扩展到复杂性状所需的理论。在本研究中,我们基于从自然群体中随机或选择性收集的样本,提出了用于检测或估计多态性标记位点与影响复杂二分性状的任何一个位点之间连锁不平衡(LD)的理论分析和方法。研究了这些方法的统计特性,并通过解析或使用蒙特卡罗模拟比较了它们的效能。结果表明,当性状和标记变体都较为常见(30%)且连锁不平衡相对较高(理论最大值的40 - 100%)时,利用表型记录和标记基因型可以以80%的效能检测到连锁不平衡。最大似然法能准确估计模型参数并检测连锁不平衡。似然法因其较高的效能和参数估计的可靠性而更受青睐。本文所开发的方法也与用于分析连续分布定量性状的方法进行了比较。结果表明,对于二分性状模型,要获得与连续性状分析相同水平的连锁不平衡检测效能,需要更大的样本量。还讨论了这些估计值在性状基因座定位中的潜在用途。

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