Department of Animal and Avian Sciences, University of Maryland, College Park, MD, USA.
Recombinetics, Saint Paul, MN, USA.
BMC Genomics. 2019 Feb 11;20(1):128. doi: 10.1186/s12864-019-5459-x.
The availability of a unique unselected Holstein line since 1964 provided a direct comparison between selected and unselected Holstein genomes whereas large Holstein samples provided unprecedented statistical power for identifying high-confidence SNP effects. Utilizing these unique resources, we aimed to identify genome changes affected by selection since 1964.
Direct comparison of genome-wide SNP markers between a Holstein line unselected since 1964 and contemporary Holsteins showed that the 40 years of artificial selection since 1964 resulted in genome landscape changes. Among the regions affected by selection, the regions containing 198 genes with fertility functions had a larger negative correlation than that of all SNPs between the SNP effects on milk yield and daughter pregnancy rate. These results supported the hypothesis that hitchhiking of genetic selection for milk production by negative effects of fertility genes contributed to the unintended declines in fertility since 1964. The genome regions subjected to selection also contained 67 immunity genes, the bovine MHC region of Chr23 with significantly decreased heterozygosity in contemporary Holsteins, and large gene clusters including T-cell receptor and immunoglobulin genes.
This study for the first time provided direct evidence that genetic selection for milk production affected fertility and immunity genes and that the hitchhiking of genetic selection for milk production by negative fertility effects contributed to the fertility declines since 1964, and identified a large number of candidate fertility and immunity genes affected by selection. The results provided novel understanding about genome changes due to artificial selection and their impact on fertility and immunity genes and could facilitate developing genetic methods to reverse the declines in fertility and immunity in Holstein cattle.
自 1964 年以来，独特的未经选择的荷斯坦牛系的存在提供了选择和未选择的荷斯坦基因组之间的直接比较，而大型荷斯坦牛样本则为确定高置信度 SNP 效应提供了前所未有的统计能力。利用这些独特的资源，我们旨在确定自 1964 年以来受选择影响的基因组变化。
自 1964 年以来未经选择的荷斯坦牛系与当代荷斯坦牛的全基因组 SNP 标记的直接比较表明，自 1964 年以来 40 年的人工选择导致了基因组景观的变化。在受选择影响的区域中，包含 198 个具有生育功能的基因的区域比所有 SNP 之间的 SNP 对产奶量和女儿妊娠率的影响具有更大的负相关。这些结果支持了这样的假设，即生育基因的负效应对产奶的遗传选择的 hitchhiking 导致了自 1964 年以来生育力的意外下降。受选择影响的基因组区域还包含 67 个免疫基因、Chr23 上的牛 MHC 区域在当代荷斯坦牛中显著降低了杂合性，以及包含 T 细胞受体和免疫球蛋白基因的大型基因簇。
本研究首次提供了直接证据，证明产奶的遗传选择影响了生育和免疫基因，产奶的遗传选择对生育基因的负效应对自 1964 年以来的生育力下降起到了 hitchhiking 的作用，并确定了大量受选择影响的生育和免疫候选基因。这些结果提供了关于人工选择引起的基因组变化及其对生育和免疫基因的影响的新认识，并为开发遗传方法来逆转荷斯坦牛的生育和免疫能力下降提供了便利。
