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非平衡群体中连锁不平衡分析的模型与算法

Model and algorithm for linkage disequilibrium analysis in a non-equilibrium population.

作者信息

Liu Jingyuan, Wang Zhong, Wang Yaqun, Li Runze, Wu Rongling

机构信息

Department of Statistics, The Pennsylvania State University State College, PA, USA.

出版信息

Front Genet. 2012 Jul 2;3:78. doi: 10.3389/fgene.2012.00078. eCollection 2012.

Abstract

The multilocus analysis of polymorphisms has emerged as a vital ingredient of population genetics and evolutionary biology. A fundamental assumption used for existing multilocus analysis approaches is Hardy-Weinberg equilibrium at which maternally- and paternally-derived gametes unite randomly during fertilization. Given the fact that natural populations are rarely panmictic, these approaches will have a significant limitation for practical use. We present a robust model for multilocus linkage disequilibrium analysis which does not rely on the assumption of random mating. This new disequilibrium model capitalizes on Weir's definition of zygotic disequilibria and is based on an open-pollinated design in which multiple maternal individuals and their half-sib families are sampled from a natural population. This design captures two levels of associations: one is at the upper level that describes the pattern of cosegregation between different loci in the parental population and the other is at the lower level that specifies the extent of co-transmission of non-alleles at different loci from parents to their offspring. An MCMC method was implemented to estimate genetic parameters that define these associations. Simulation studies were used to validate the statistical behavior of the new model.

摘要

多基因座多态性分析已成为群体遗传学和进化生物学的重要组成部分。现有多基因座分析方法所使用的一个基本假设是哈迪-温伯格平衡,即在受精过程中,来自母本和父本的配子随机结合。鉴于自然种群很少是随机交配的,这些方法在实际应用中将存在重大局限性。我们提出了一种用于多基因座连锁不平衡分析的稳健模型,该模型不依赖于随机交配的假设。这种新的不平衡模型利用了韦尔对合子不平衡的定义,并且基于一种开放授粉设计,其中从自然种群中采样多个母本个体及其半同胞家系。这种设计捕捉了两个层次的关联:一个是在较高层次,描述亲代群体中不同基因座之间的共分离模式;另一个是在较低层次,指定不同基因座上的非等位基因从亲本到其后代的共传递程度。实施了一种马尔可夫链蒙特卡罗(MCMC)方法来估计定义这些关联的遗传参数。通过模拟研究来验证新模型的统计行为。

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