4.7 Article

Identifying pleiotropic variants and candidate genes for fertility and reproduction traits in Holstein cattle via association studies based on imputed whole-genome sequence genotypes

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BMC GENOMICS
卷 23, 期 1, 页码 -

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BMC
DOI: 10.1186/s12864-022-08555-z

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Cattle breeding; Genome-wide association study; GWAS; QTL; Whole-genome sequence variants

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In this study, a genome-wide association study was conducted to identify important SNPs and candidate genes associated with fertility and reproduction traits in Holstein cattle. The results provide valuable insights into the biological mechanisms underlying these traits.
Background Genetic progress for fertility and reproduction traits in dairy cattle has been limited due to the low heritability of most indicator traits. Moreover, most of the quantitative trait loci (QTL) and candidate genes associated with these traits remain unknown. In this study, we used 5.6 million imputed DNA sequence variants (single nucleotide polymorphisms, SNPs) for genome-wide association studies (GWAS) of 18 fertility and reproduction traits in Holstein cattle. Aiming to identify pleiotropic variants and increase detection power, multiple-trait analyses were performed using a method to efficiently combine the estimated SNP effects of single-trait GWAS based on a chi-square statistic. Results There were 87, 72, and 84 significant SNPs identified for heifer, cow, and sire traits, respectively, which showed a wide and distinct distribution across the genome, suggesting that they have relatively distinct polygenic nature. The biological functions of immune response and fatty acid metabolism were significantly enriched for the 184 and 124 positional candidate genes identified for heifer and cow traits, respectively. No known biological function was significantly enriched for the 147 positional candidate genes found for sire traits. The most important chromosomes that had three or more significant QTL identified are BTA22 and BTA23 for heifer traits, BTA8 and BTA17 for cow traits, and BTA4, BTA7, BTA17, BTA22, BTA25, and BTA28 for sire traits. Several novel and biologically important positional candidate genes were strongly suggested for heifer (SOD2, WTAP, DLEC1, PFKFB4, TRIM27, HECW1, DNAH17, and ADAM3A), cow (ANXA1, PCSK5, SPESP1, and JMJD1C), and sire (ELMO1, CFAP70, SOX30, DGCR8, SEPTIN14, PAPOLB, JMJD1C, and NELL2) traits. Conclusions These findings contribute to better understand the underlying biological mechanisms of fertility and reproduction traits measured in heifers, cows, and sires, which may contribute to improve genomic evaluation for these traits in dairy cattle.

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