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基因组选择中的新兴问题。

Emerging issues in genomic selection.

机构信息

Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.

Instituto Nacional de Investigación Agropecuaria (INIA), 90200 Canelones, Uruguay.

出版信息

J Anim Sci. 2021 Jun 1;99(6). doi: 10.1093/jas/skab092.

Abstract

Genomic selection (GS) is now practiced successfully across many species. However, many questions remain, such as long-term effects, estimations of genomic parameters, robustness of genome-wide association study (GWAS) with small and large datasets, and stability of genomic predictions. This study summarizes presentations from the authors at the 2020 American Society of Animal Science (ASAS) symposium. The focus of many studies until now is on linkage disequilibrium between two loci. Ignoring higher-level equilibrium may lead to phantom dominance and epistasis. The Bulmer effect leads to a reduction of the additive variance; however, the selection for increased recombination rate can release anew genetic variance. With genomic information, estimates of genetic parameters may be biased by genomic preselection, but costs of estimation can increase drastically due to the dense form of the genomic information. To make the computation of estimates feasible, genotypes could be retained only for the most important animals, and methods of estimation should use algorithms that can recognize dense blocks in sparse matrices. GWASs using small genomic datasets frequently find many marker-trait associations, whereas studies using much bigger datasets find only a few. Most of the current tools use very simple models for GWAS, possibly causing artifacts. These models are adequate for large datasets where pseudo-phenotypes such as deregressed proofs indirectly account for important effects for traits of interest. Artifacts arising in GWAS with small datasets can be minimized by using data from all animals (whether genotyped or not), realistic models, and methods that account for population structure. Recent developments permit the computation of P-values from genomic best linear unbiased prediction (GBLUP), where models can be arbitrarily complex but restricted to genotyped animals only, and single-step GBLUP that also uses phenotypes from ungenotyped animals. Stability was an important part of nongenomic evaluations, where genetic predictions were stable in the absence of new data even with low prediction accuracies. Unfortunately, genomic evaluations for such animals change because all animals with genotypes are connected. A top-ranked animal can easily drop in the next evaluation, causing a crisis of confidence in genomic evaluations. While correlations between consecutive genomic evaluations are high, outliers can have differences as high as 1 SD. A solution to fluctuating genomic evaluations is to base selection decisions on groups of animals. Although many issues in GS have been solved, many new issues that require additional research continue to surface.

摘要

基因组选择(GS)现在已经成功应用于许多物种。然而,仍有许多问题需要解决,例如长期影响、基因组参数的估计、小数据集和大数据集下全基因组关联研究(GWAS)的稳健性,以及基因组预测的稳定性。本研究总结了作者在 2020 年美国动物科学协会(ASAS)专题讨论会上的演讲内容。到目前为止,许多研究的重点都集中在两个基因座之间的连锁不平衡上。忽略更高层次的平衡可能导致显性和上位性的假象。布尔默效应导致加性方差减少;然而,选择增加重组率可以释放新的遗传方差。利用基因组信息,遗传参数的估计可能会受到基因组预选的影响,但由于基因组信息的密集形式,估计成本可能会大幅增加。为了使估计的计算可行,可以只保留最重要动物的基因型,并且估计方法应该使用可以识别稀疏矩阵中密集块的算法。使用小基因组数据集进行的 GWAS 经常会发现许多标记-性状关联,而使用更大数据集的研究则只发现少数关联。目前大多数工具都使用非常简单的 GWAS 模型,这可能会导致假象。这些模型对于大型数据集是足够的,在这些数据集中,例如去回归证明等伪表型可以间接解释感兴趣性状的重要影响。在使用小数据集进行 GWAS 时,可以通过使用所有动物的数据(无论是否被基因型化)、现实的模型和考虑群体结构的方法来最小化假象。最近的发展允许从基因组最佳线性无偏预测(GBLUP)中计算 P 值,其中模型可以任意复杂,但仅限于被基因型化的动物,并且单步 GBLUP 也可以使用未被基因型化的动物的表型。稳定性是非基因组评估的一个重要部分,在没有新数据的情况下,即使预测准确性较低,遗传预测也能保持稳定。不幸的是,由于所有具有基因型的动物都相互关联,因此对于这些动物的基因组评估会发生变化。排名靠前的动物很容易在下一次评估中下降,导致对基因组评估的信心危机。虽然连续的基因组评估之间的相关性很高,但异常值之间的差异可以高达 1 个标准差。解决基因组评估波动的方法是根据动物群体做出选择决策。尽管 GS 中的许多问题已经得到解决,但仍有许多需要进一步研究的新问题继续出现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140b/8186541/4c43ebc3cd7c/skab092_fig1.jpg

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