Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, PO Box 65, 8200 AB Lelystad, The Netherlands.
Genet Sel Evol. 2010 Mar 22;42(1):10. doi: 10.1186/1297-9686-42-10.
In livestock populations, missing genotypes on a large proportion of animals are a major problem to implement the estimation of marker-assisted breeding values using haplotypes. The objective of this article is to develop a method to predict haplotypes of animals that are not genotyped using mixed model equations and to investigate the effect of using these predicted haplotypes on the accuracy of marker-assisted breeding value estimation.
For genotyped animals, haplotypes were determined and for each animal the number of haplotype copies (nhc) was counted, i.e. 0, 1 or 2 copies. In a mixed model framework, nhc for each haplotype were predicted for ungenotyped animals as well as for genotyped animals using the additive genetic relationship matrix. The heritability of nhc was assumed to be 0.99, allowing for minor genotyping and haplotyping errors. The predicted nhc were subsequently used in marker-assisted breeding value estimation by applying random regression on these covariables. To evaluate the method, a population was simulated with one additive QTL and an additive polygenic genetic effect. The QTL was located in the middle of a haplotype based on SNP-markers.
The accuracy of predicted haplotype copies for ungenotyped animals ranged between 0.59 and 0.64 depending on haplotype length. Because powerful BLUP-software was used, the method was computationally very efficient. The accuracy of total EBV increased for genotyped animals when marker-assisted breeding value estimation was compared with conventional breeding value estimation, but for ungenotyped animals the increase was marginal unless the heritability was smaller than 0.1. Haplotypes based on four markers yielded the highest accuracies and when only the nearest left marker was used, it yielded the lowest accuracy. The accuracy increased with increasing marker density. Accuracy of the total EBV approached that of gene-assisted BLUP when 4-marker haplotypes were used with a distance of 0.1 cM between the markers.
The proposed method is computationally very efficient and suitable for marker-assisted breeding value estimation in large livestock populations including effects of a number of known QTL. Marker-assisted breeding value estimation using predicted haplotypes increases accuracy especially for traits with low heritability.
在畜牧业中，很大一部分动物的基因型缺失是一个主要问题，这使得使用单倍型估计标记辅助育种值变得困难。本文的目的是开发一种方法，通过混合模型方程预测未进行基因分型的动物的单倍型，并研究使用这些预测单倍型对标记辅助育种值估计准确性的影响。
对于已进行基因分型的动物，确定了其单倍型，并统计了每个动物的单倍型拷贝数（nhc），即 0、1 或 2 个拷贝。在混合模型框架中，使用加性遗传关系矩阵预测未进行基因分型的动物以及已进行基因分型的动物的 nhc。假设 nhc 的遗传力为 0.99，允许存在轻微的基因分型和单倍型错误。随后，通过对这些协变量应用随机回归，将预测的 nhc 用于标记辅助育种值估计。为了评估该方法，使用一个具有一个加性 QTL 和一个加性多基因遗传效应的群体进行模拟。QTL 位于基于 SNP 标记的单倍型中间。
未进行基因分型的动物的预测单倍型拷贝的准确性范围在 0.59 到 0.64 之间，具体取决于单倍型的长度。由于使用了功能强大的 BLUP 软件，该方法在计算上非常高效。与传统的育种值估计相比，标记辅助育种值估计可提高已进行基因分型动物的总 EBV 准确性，但对于未进行基因分型的动物，除非遗传力小于 0.1，否则增加幅度较小。基于四个标记的单倍型产生了最高的准确性，而仅使用最接近的左侧标记时，准确性最低。随着标记密度的增加，准确性也随之提高。当使用距离为 0.1 cM 的四个标记的四标记单倍型时，总 EBV 的准确性接近基因辅助 BLUP。
该方法在计算上非常高效，适用于包括多个已知 QTL 影响的大型家畜群体的标记辅助育种值估计。使用预测单倍型进行标记辅助育种值估计可提高准确性，特别是对于遗传力较低的性状。
