基于全基因组序列基因型的关联研究鉴定荷斯坦奶牛的多效变异体和生育与繁殖性状的候选基因。

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

机构信息

Department of Animal Sciences, Purdue University, 270 S. Russell Street, West Lafayette, IN, 47907-2041, USA.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.

出版信息

BMC Genomics. 2022 Apr 28;23(1):331. doi: 10.1186/s12864-022-08555-z.

DOI:10.1186/s12864-022-08555-z

PMID:35484513

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9052698/

Abstract

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.

摘要

背景

由于大多数指示性状的遗传力较低，奶牛的繁殖力和繁殖性状的遗传进展一直受到限制。此外，大多数与这些性状相关的数量性状基因座（QTL）和候选基因仍然未知。在这项研究中，我们使用了 560 万个已推断的 DNA 序列变异（单核苷酸多态性，SNP），对荷斯坦奶牛的 18 个繁殖力和繁殖性状进行了全基因组关联研究（GWAS）。为了鉴定多效变异并提高检测能力，我们使用一种基于卡方统计的有效组合单性状 GWAS 中估计 SNP 效应的方法进行了多性状分析。

结果

在小母牛、母牛和公牛性状中分别鉴定出 87、72 和 84 个显著 SNP，这些 SNP 在基因组中分布广泛且明显，表明它们具有相对独特的多基因性质。在为小母牛和母牛性状分别鉴定的 184 个和 124 个定位候选基因中，免疫反应和脂肪酸代谢的生物学功能显著富集。在为公牛性状鉴定的 147 个定位候选基因中，没有发现显著富集的已知生物学功能。在鉴定出三个或更多显著 QTL 的最重要染色体中，小母牛性状是 BTA22 和 BTA23，母牛性状是 BTA8 和 BTA17，公牛性状是 BTA4、BTA7、BTA17、BTA22、BTA25 和 BTA28。对于小母牛（SOD2、WTAP、DLEC1、PFKFB4、TRIM27、HECW1、DNAH17 和 ADAM3A）、母牛（ANXA1、PCSK5、SPESP1 和 JMJD1C）和公牛（ELMO1、CFAP70、SOX30、DGCR8、SEPTIN14、PAPOLB、JMJD1C 和 NELL2）性状，强烈提示了一些新的和重要的定位候选基因。