ISAG Bursary Award: eQTL mapping in beef cows to identify genetic variants underlying fertility; ISAG 2023: 39th International Society of Animal Genetics Conference

The cow-calf industry’s sustainability and profitability depend on the reproductive success of the herd. Genomic information has provided insights into the quantitative trait loci (QTLs) underlying cow subfertility. Integrating functional information into the genomics regulatory layer can provide new markers for improving fertility. This study aims to identify gene expression regulatory polymorphisms in uterine luminal epithelial cells and investigate their effects on fertility-related genes. We retrieved RNA-Seq data from uterine epithelial cells (GSE171577) of recipient cows (n = 18 non-pregnant – NP and n = 25 pregnant – P) sampled on day four before embryo transfer. Raw data quality control was performed, and read mapping was carried out using the multi-sample 2-pass mapping procedure from STAR. Gene normalization was performed using the log2CPM function from edgeR. Variant detection was based on the uniquely mapped reads using the GATK software. After quality control, 43 samples, 203,404 SNPs, and 15,029 genes were used for eQTL analysis (expression quantitative trait loci). Using an additive linear model from the MatrixEQTL R-package, we identified 25,946 cis-eQTLs for 1,823 genes (FDR < 0.05). Chromosomes 18 and 19 harbored the greatest number of cis-eQTLs with 2,392 and 2,283, respectively. A total of 50 cis-eQTLs were previously reported as differentially expressed genes, including CD37, CXCL3, PILRA, and PPP6R1 genes. We also identified fertility-related genes such as PLOD3, HDHD3, and LY6G6E, which were modulated by 106, 86, and 65 SNPs, respectively. Functional analysis of cis-eQTLs retrieved immune-related biologic processes, including antigen processing and presentation of peptide antigen via MHC class Ib and defense response to Gram-positive bacterium (FDR < 0.05). Additionally, fatty acid degradation and metabolic pathways were among the over-represented KEGG pathways. Our findings show that eQTLs influence key biological pathways and genes affecting fertility. Additionally, it provides novel functional regulatory mechanisms that may lead to the identification of causative mutations.