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基于全基因组标记物,在贝叶斯方法预测遗传值时纳入非加性遗传效应。

Including non-additive genetic effects in Bayesian methods for the prediction of genetic values based on genome-wide markers.

机构信息

Research Unit Genetics and Biometry, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.

出版信息

BMC Genet. 2011 Aug 25;12:74. doi: 10.1186/1471-2156-12-74.

Abstract

BACKGROUND

Molecular marker information is a common source to draw inferences about the relationship between genetic and phenotypic variation. Genetic effects are often modelled as additively acting marker allele effects. The true mode of biological action can, of course, be different from this plain assumption. One possibility to better understand the genetic architecture of complex traits is to include intra-locus (dominance) and inter-locus (epistasis) interaction of alleles as well as the additive genetic effects when fitting a model to a trait. Several Bayesian MCMC approaches exist for the genome-wide estimation of genetic effects with high accuracy of genetic value prediction. Including pairwise interaction for thousands of loci would probably go beyond the scope of such a sampling algorithm because then millions of effects are to be estimated simultaneously leading to months of computation time. Alternative solving strategies are required when epistasis is studied.

METHODS

We extended a fast Bayesian method (fBayesB), which was previously proposed for a purely additive model, to include non-additive effects. The fBayesB approach was used to estimate genetic effects on the basis of simulated datasets. Different scenarios were simulated to study the loss of accuracy of prediction, if epistatic effects were not simulated but modelled and vice versa.

RESULTS

If 23 QTL were simulated to cause additive and dominance effects, both fBayesB and a conventional MCMC sampler BayesB yielded similar results in terms of accuracy of genetic value prediction and bias of variance component estimation based on a model including additive and dominance effects. Applying fBayesB to data with epistasis, accuracy could be improved by 5% when all pairwise interactions were modelled as well. The accuracy decreased more than 20% if genetic variation was spread over 230 QTL. In this scenario, accuracy based on modelling only additive and dominance effects was generally superior to that of the complex model including epistatic effects.

CONCLUSIONS

This simulation study showed that the fBayesB approach is convenient for genetic value prediction. Jointly estimating additive and non-additive effects (especially dominance) has reasonable impact on the accuracy of prediction and the proportion of genetic variation assigned to the additive genetic source.

摘要

背景

分子标记信息是推断遗传变异与表型变异之间关系的常用来源。遗传效应通常被建模为加性标记等位基因效应。当然,真实的生物学作用模式可能与这一简单的假设不同。更好地理解复杂性状的遗传结构的一种可能性是,在拟合模型时,包括等位基因的基因内(显性)和基因间(上位性)相互作用以及加性遗传效应。有几种贝叶斯 MCMC 方法可用于全基因组遗传效应的估计,从而可以高精度地预测遗传值。对数千个基因座进行成对相互作用的估计可能会超出此类采样算法的范围,因为那样需要同时估计数百万个效应,从而导致数月的计算时间。当研究上位性时,需要采用替代的求解策略。

方法

我们扩展了一种快速贝叶斯方法(fBayesB),该方法以前是针对纯加性模型提出的,现在将其扩展到包括非加性效应。该方法用于根据模拟数据集估计遗传效应。模拟了不同的情景,以研究如果不模拟上位性效应而只对其进行建模或者反之,预测准确性的损失情况。

结果

如果模拟 23 个 QTL 引起加性和显性效应,那么基于包括加性和显性效应的模型,fBayesB 和传统的 MCMC 抽样器 BayesB 在遗传值预测准确性和方差分量估计偏差方面的结果相似。将 fBayesB 应用于具有上位性的数据,如果将所有成对相互作用都建模为模型,则可以将准确性提高 5%。如果遗传变异分布在 230 个 QTL 上,则准确性会下降超过 20%。在这种情况下,基于仅建模加性和显性效应的模型的准确性通常优于包括上位性效应的复杂模型。

结论

这项模拟研究表明,fBayesB 方法便于进行遗传值预测。联合估计加性和非加性效应(特别是显性效应)对预测准确性和分配给加性遗传源的遗传变异比例有合理的影响。

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