Agriculture Victoria, AgriBio, Centre of AgriBioscience, 5 Ring Road, Bundoora, VIC, 3082, Australia.
School of Applied Systems Biology, La Trobe University, Bundoora, VIC, 3083, Australia.
Genet Sel Evol. 2024 Jun 6;56(1):42. doi: 10.1186/s12711-024-00912-8.
Female fertility is an important trait in dairy cattle. Identifying putative causal variants associated with fertility may help to improve the accuracy of genomic prediction of fertility. Combining expression data (eQTL) of genes, exons, gene splicing and allele specific expression is a promising approach to fine map QTL to get closer to the causal mutations. Another approach is to identify genomic differences between cows selected for high and low fertility and a selection experiment in New Zealand has created exactly this resource. Our objective was to combine multiple types of expression data, fertility traits and allele frequency in high- (POS) and low-fertility (NEG) cows with a genome-wide association study (GWAS) on calving interval in Australian cows to fine-map QTL associated with fertility in both Australia and New Zealand dairy cattle populations.
Variants that were significantly associated with calving interval (CI) were strongly enriched for variants associated with gene, exon, gene splicing and allele-specific expression, indicating that there is substantial overlap between QTL associated with CI and eQTL. We identified 671 genes with significant differential expression between POS and NEG cows, with the largest fold change detected for the CCDC196 gene on chromosome 10. Our results provide numerous candidate genes associated with female fertility in dairy cattle, including GYS2 and TIGAR on chromosome 5 and SYT3 and HSD17B14 on chromosome 18. Multiple QTL regions were located in regions with large numbers of copy number variants (CNV). To identify the causal mutations for these variants, long read sequencing may be useful.
Variants that were significantly associated with CI were highly enriched for eQTL. We detected 671 genes that were differentially expressed between POS and NEG cows. Several QTL detected for CI overlapped with eQTL, providing candidate genes for fertility in dairy cattle.
雌性生育力是奶牛的一个重要特征。鉴定与生育力相关的潜在因果变异可有助于提高生育力基因组预测的准确性。结合基因、外显子、基因剪接和等位基因特异性表达的表达数据（eQTL）是精细定位 QTL 以更接近因果突变的有前途的方法。另一种方法是鉴定在高（POS）和低（NEG）生育力牛之间选择的基因组差异，新西兰的一个选择实验恰好创建了这种资源。我们的目标是结合澳大利亚奶牛产犊间隔的全基因组关联研究（GWAS），将高（POS）和低（NEG）奶牛的多种类型的表达数据、生育力性状和等位基因频率与新西兰奶牛的选择实验相结合，以精细定位与澳大利亚和新西兰奶牛群体生育力相关的 QTL。
与产犊间隔（CI）显著相关的变体强烈富集与基因、外显子、基因剪接和等位基因特异性表达相关的变体，表明与 CI 相关的 QTL 与 eQTL 之间存在大量重叠。我们鉴定了 671 个在 POS 和 NEG 牛之间差异表达的基因，其中在 10 号染色体上的 CCDC196 基因中检测到的最大折叠变化。我们的结果提供了许多与奶牛雌性生育力相关的候选基因，包括 5 号染色体上的 GYS2 和 TIGAR 以及 18 号染色体上的 SYT3 和 HSD17B14。多个 QTL 区域位于包含大量拷贝数变异（CNV）的区域。为了识别这些变体的因果突变，长读测序可能是有用的。
与 CI 显著相关的变体高度富集 eQTL。我们检测到在 POS 和 NEG 牛之间差异表达的 671 个基因。几个检测到的与 CI 相关的 QTL 与 eQTL 重叠，为奶牛的生育力提供了候选基因。
