Yang Rong-Cai
Alberta Agriculture, Food and Rural Development, Edmonton, Alberta T6H 5T6, Canada.
Genetics. 2004 Jul;167(3):1493-505. doi: 10.1534/genetics.103.020016.
Modeling and detecting nonallelic (epistatic) effects at multiple quantitative trait loci (QTL) often assume that the study population is in zygotic equilibrium (i.e., genotypic frequencies at different loci are products of corresponding single-locus genotypic frequencies). However, zygotic associations can arise from physical linkages between different loci or from many evolutionary and demographic processes even for unlinked loci. We describe a new model that partitions the two-locus genotypic values in a zygotic disequilibrium population into equilibrium and residual portions. The residual portion is of course due to the presence of zygotic associations. The equilibrium portion has eight components including epistatic effects that can be defined under three commonly used equilibrium models, Cockerham's model, F2-metric, and F(infinity)-metric models. We evaluate our model along with these equilibrium models theoretically and empirically. While all the equilibrium models require zygotic equilibrium, Cockerham's model is the most general, allowing for Hardy-Weinberg disequilibrium and arbitrary gene frequencies at individual loci whereas F2-metric and F(infinity)-metric models require gene frequencies of one-half in a Hardy-Weinberg equilibrium population. In an F2 population with two unlinked loci, Cockerham's model is reduced to the F2-metric model and thus both have a desirable property of orthogonality among the genic effects; the genic effects under the F(infinity)-metric model are not orthogonal but they can be easily translated into those under the F2-metric model through a simple relation. Our model is reduced to these equilibrium models in the absence of zygotic associations. The results from our empirical analysis suggest that the residual genetic variance arising from zygotic associations can be substantial and may be an important source of bias in QTL mapping studies.
对多个数量性状基因座（QTL）的非等位基因（上位性）效应进行建模和检测时，通常假定研究群体处于合子平衡状态（即不同基因座的基因型频率是相应单基因座基因型频率的乘积）。然而，即使对于不连锁的基因座，合子关联也可能源于不同基因座之间的物理连锁，或者许多进化和人口统计学过程。我们描述了一种新模型，该模型将处于合子不平衡群体中的两位点基因型值划分为平衡部分和残差部分。残差部分当然是由于合子关联的存在。平衡部分有八个组成部分，包括可以在三种常用平衡模型（科克伦模型、F2度量模型和F(∞)度量模型）下定义的上位性效应。我们从理论和实证两方面对我们的模型以及这些平衡模型进行了评估。虽然所有平衡模型都要求合子平衡，但科克伦模型最为通用，允许哈迪-温伯格不平衡以及各个基因座上的任意基因频率，而F2度量模型和F(∞)度量模型则要求哈迪-温伯格平衡群体中的基因频率为二分之一。在具有两个不连锁基因座的F2群体中，科克伦模型简化为F2度量模型，因此二者在基因效应之间都具有理想的正交性；F(∞)度量模型下的基因效应不是正交的，但通过一个简单关系可以很容易地将其转化为F2度量模型下的基因效应。在不存在合子关联的情况下，我们的模型简化为这些平衡模型。我们实证分析的结果表明，合子关联产生的残差遗传方差可能很大，并且可能是QTL定位研究中偏差的一个重要来源。
