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两阶段逼近法分析大型家系中混合遗传模型。

A two-stage approximation for analysis of mixture genetic models in large pedigrees.

机构信息

Institute of Animal Breeding and Husbandry, Christian-Albrechts University of Kiel, 24098 Kiel, Germany.

出版信息

Genetics. 2010 Jun;185(2):655-70. doi: 10.1534/genetics.110.115774. Epub 2010 Apr 9.

DOI:10.1534/genetics.110.115774
PMID:20382829
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2881145/
Abstract

Information from cosegregation of marker and QTL alleles, in addition to linkage disequilibrium (LD), can improve genomic selection. Variance components linear models have been proposed for this purpose, but accommodating dominance and epistasis is not straightforward with them. A full-Bayesian analysis of a mixture genetic model is favorable in this respect, but is computationally infeasible for whole-genome analyses. Thus, we propose an approximate two-step approach that neglects information from trait phenotypes in inferring ordered genotypes and segregation indicators of markers. Quantitative trait loci (QTL) fine-mapping scenarios, using high-density markers and pedigrees of five generations without genotyped females, were simulated to test this strategy against an exact full-Bayesian approach. The latter performed better in estimating QTL genotypes, but precision of QTL location and accuracy of genomic breeding values (GEBVs) did not differ for the two methods at realistically low LD. If, however, LD was higher, the exact approach resulted in a slightly higher accuracy of GEBVs. In conclusion, the two-step approach makes mixture genetic models computationally feasible for high-density markers and large pedigrees. Furthermore, markers need to be sampled only once and results can be used for the analysis of all traits. Further research is needed to evaluate the two-step approach for complex pedigrees and to analyze alternative strategies for modeling LD between QTL and markers.

摘要

除连锁不平衡(LD)外,标记和 QTL 等位基因的共分离信息也可以改进基因组选择。为此已经提出了方差分量线性模型,但用这些模型直接容纳显性和上位性并不容易。混合遗传模型的全贝叶斯分析在这方面是有利的,但对于全基因组分析来说计算上是不可行的。因此,我们提出了一种近似的两步方法,该方法在推断有序基因型和标记的分离指标时忽略了来自性状表型的信息。使用高密度标记和五代无基因型雌性的系谱模拟了 QTL 精细定位场景,以比较这种策略与精确的全贝叶斯方法。后者在估计 QTL 基因型方面表现更好,但在实际低 LD 下,两种方法的 QTL 位置精度和基因组育种值(GEBV)的准确性没有差异。然而,如果 LD 更高,精确方法会导致 GEBV 的准确性略有提高。总之,两步方法使混合遗传模型在高密度标记和大型系谱中具有计算可行性。此外,仅需对标记进行一次采样,并且结果可用于分析所有性状。需要进一步研究两步方法在复杂系谱中的应用,并分析替代模型 QTL 和标记之间 LD 的策略。

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引用本文的文献

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A class of Bayesian methods to combine large numbers of genotyped and non-genotyped animals for whole-genome analyses.一类用于全基因组分析的贝叶斯方法,可结合大量基因分型和未基因分型的动物。
Genet Sel Evol. 2014 Sep 22;46(1):50. doi: 10.1186/1297-9686-46-50.
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Association mapping in an elite maize breeding population.关联作图在一个优秀的玉米育种群体中的应用。
Theor Appl Genet. 2011 Sep;123(5):847-58. doi: 10.1007/s00122-011-1631-7. Epub 2011 Jun 17.
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Mapping QTLs with main and epistatic effects underlying grain yield and heading time in soft winter wheat.定位软冬小麦产量和抽穗期的主效和上位效 QTL。
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本文引用的文献

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The impact of genetic relationship information on genomic breeding values in German Holstein cattle.遗传关系信息对德国荷斯坦奶牛基因组育种值的影响。
Genet Sel Evol. 2010 Feb 19;42(1):5. doi: 10.1186/1297-9686-42-5.
2
Linear models for joint association and linkage QTL mapping.用于联合关联和连锁QTL定位的线性模型。
Genet Sel Evol. 2009 Sep 29;41(1):43. doi: 10.1186/1297-9686-41-43.
3
Detection of sharing by descent, long-range phasing and haplotype imputation.通过血缘共享、长程定相和单倍型填充进行检测。
Nat Genet. 2008 Sep;40(9):1068-75. doi: 10.1038/ng.216.
4
Invited review: Genomic selection in dairy cattle: progress and challenges.特邀综述:奶牛的基因组选择:进展与挑战
J Dairy Sci. 2009 Feb;92(2):433-43. doi: 10.3168/jds.2008-1646.
5
Invited review: reliability of genomic predictions for North American Holstein bulls.特邀综述:北美荷斯坦公牛基因组预测的可靠性
J Dairy Sci. 2009 Jan;92(1):16-24. doi: 10.3168/jds.2008-1514.
6
Linkage disequilibrium and persistence of phase in Holstein-Friesian, Jersey and Angus cattle.荷斯坦奶牛、泽西奶牛和安格斯牛的连锁不平衡与相位持续性
Genetics. 2008 Jul;179(3):1503-12. doi: 10.1534/genetics.107.084301. Epub 2008 Jul 13.
7
Accuracy of genomic selection using different methods to define haplotypes.使用不同方法定义单倍型时基因组选择的准确性。
Genetics. 2008 Jan;178(1):553-61. doi: 10.1534/genetics.107.080838.
8
The impact of genetic relationship information on genome-assisted breeding values.遗传关系信息对基因组辅助育种值的影响。
Genetics. 2007 Dec;177(4):2389-97. doi: 10.1534/genetics.107.081190.
9
Improved techniques for sampling complex pedigrees with the Gibbs sampler.使用吉布斯采样器对复杂谱系进行采样的改进技术。
Genet Sel Evol. 2007 Jan-Feb;39(1):27-38. doi: 10.1186/1297-9686-39-1-27. Epub 2007 Jan 11.
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Optimal haplotype structure for linkage disequilibrium-based fine mapping of quantitative trait loci using identity by descent.基于家系同一性的数量性状基因座连锁不平衡精细定位的最佳单倍型结构
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