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随着世代推移,估计的基因组育种值出现衰减是由于标记与数量性状基因座之间存在长距离关联。

Erosion of estimated genomic breeding values with generations is due to long distance associations between markers and QTL.

作者信息

Boichard Didier, Fritz Sébastien, Croiseau Pascal, Ducrocq Vincent, Tribout Thierry, Cuyabano Beatriz C D

机构信息

Université Paris-Saclay, INRAE, AgroParisTech, GABI, 78350, Jouy-en-Josas, France.

Eliance, 75012, Paris, France.

出版信息

Genet Sel Evol. 2025 Mar 21;57(1):14. doi: 10.1186/s12711-025-00963-5.

Abstract

BACKGROUND

Most validation studies of genomic evaluations on candidates (prior to observing phenotypes) present inflation of their predicted breeding values, i.e., regression coefficients of their later observed phenotypes on the early predictions are smaller than one. The aim of this study was to show that this inflation pattern reflects at least partly long-distance associations between markers and quantitative trait loci (QTL) in the reference population and to propose methods to estimate the corresponding "erosion" coefficient.

RESULTS

Across-chromosome linkage disequilibrium (LD) is observed in different dairy cattle breeds, being a result from limited effective population size and from relationships within the reference population. Due to this long distance LD, the estimated SNP effects capture non-zero contributions from distant QTLs, some located on other chromosomes than the SNP itself. Therefore, corresponding SNP effects are partly lost in the next generations and we refer to this loss as "erosion". With the concept of QTL contribution to SNP effects derived from mixed model equations, we show with simulation that this long range LD explains 6-25% of the variance of the estimated genomic breeding values, a proportion that is unchanged when the evaluation model includes a residual polygenic effect. Two methods are proposed to predict this erosion factor assuming known simulated QTL effects. In Method 1, one generation of progeny is simulated from the reference population and the GEBV of these progeny based on SNP effects estimated in this newly simulated generation are regressed on the GEBV of the same progeny based on SNP effects estimated in the reference population. In Method 2 all the QTL contributions to SNP effects are regressed based on SNP-QTL recombination rates and summed to predict the GEBV at the next generation. The regression coefficient of the GEBV based on eroded contributions on the raw GEBV is also an estimate of erosion. An illustration is given with the French Normande female reference bovine population in 2021, showing erosion factors ranging from 0.84 to 0.87.

CONCLUSION

Accounting for erosion is important to avoid inflation and biased predictions. The ways to both reduce inflation and to correct for it in the prediction are discussed.

摘要

背景

大多数针对候选个体(在观察表型之前)的基因组评估验证研究中,其预测育种值存在夸大现象,即后期观察到的表型对早期预测的回归系数小于1。本研究的目的是表明这种夸大模式至少部分反映了参考群体中标记与数量性状位点(QTL)之间的长距离关联,并提出估计相应“侵蚀”系数的方法。

结果

在不同奶牛品种中观察到跨染色体连锁不平衡(LD),这是有效群体规模有限以及参考群体内亲缘关系的结果。由于这种长距离LD,估计的SNP效应捕获了来自远处QTL的非零贡献,其中一些QTL位于与SNP本身不同的染色体上。因此,相应的SNP效应在下一代中会部分丢失,我们将这种丢失称为“侵蚀”。利用从混合模型方程推导的QTL对SNP效应的贡献概念,我们通过模拟表明,这种长距离LD解释了估计的基因组育种值方差的6%-25%,当评估模型包含残余多基因效应时,该比例不变。提出了两种方法来预测这种侵蚀因子,假设已知模拟的QTL效应。在方法1中,从参考群体模拟一代后代,并将基于在这个新模拟世代中估计的SNP效应的这些后代的基因组估计育种值(GEBV),对基于在参考群体中估计的SNP效应的相同后代的GEBV进行回归。在方法2中,基于SNP-QTL重组率对所有QTL对SNP效应的贡献进行回归,并求和以预测下一代的GEBV。基于侵蚀贡献的GEBV对原始GEBV的回归系数也是侵蚀的估计值。以2021年法国诺曼底雌性参考牛群为例进行说明,显示侵蚀因子范围为0.84至0.87。

结论

考虑侵蚀对于避免夸大和有偏差的预测很重要。讨论了在预测中减少夸大并对其进行校正的方法。

相似文献

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Genomic selection in dairy cattle simulated populations.奶牛模拟群体中的基因组选择
J Dairy Res. 2018 May;85(2):125-132. doi: 10.1017/S0022029918000304.

本文引用的文献

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Predicting the accuracy of genomic predictions.预测基因组预测的准确性。
Genet Sel Evol. 2021 Jun 29;53(1):55. doi: 10.1186/s12711-021-00647-w.
8

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