Gene Set Enrichment Analysis Using Single Nucleotide Polymorphisms to Identify Genes Associated with Residual Feed Intake in Cattle
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Feed comprises 66% and 77% of the total cost of beef cattle calf and yearling finishing systems, respectively. Heritabilities for feed intake and feed efficiency (FE, estimated as residual feed intake, or RFI) have ranged from 0.08 to 0.46 in previous studies, highlighting the potential for genetic selection to bring about significant gains in feed efficiency and profitability within the beef industry. The objective of this study was to identify gene pathways significant for FE (as measured by RFI) through the use of Gene set enrichment analysis-single nucleotide polymorphism (GSEA-SNP) using single nucleotide polymorphisms (SNPs) as proxies for bovine genes. A population of 847 Hereford cattle (181 purebreds and 666 Hereford cross animals) consisting of 23 females and 824 males ranging in age from 210 to 496 d from a single ranch were evaluated for a period ranging from 70 to 140 days on feed (DOF). Only 31 animals were fed over 72 days. Average daily gain (ADG), dry matter intake (DMI), initial weight (IW), mid-test metabolic weight (MMWT), and DOF were recorded across the feeding period for each individual. Covariates for the genome-wide association study (GWAS) were age, % Hereford, and a series of 6 contemporary groups based on harvest date. GWAS was followed by GSEA-SNP of SNP data with Bos taurus gene sets sourced from GO, KEGG, Panther, Reactome, and Metacyc. A total of 20,692 bovine genes were mapped within gene sets, and proxy SNPs were mapped to genes located within 20 kilobase pairs. The null distribution of the GSEA-SNP test statistic was approximated using 10,000 permutations. A majority of genotypes were obtained from the Illumina bovine HD BeadChip, while the remainder were obtained using the Illumina bovine 50K BeadChip and imputed to 778,000 SNPs using Beagle. The Metacyc pathway ‘metabolism of proteins’ with 257 genes tended towards significance for RFI with a normalized enrichment score (NES) of 2.917. There were a total of 108 leading edge genes in the pathway. The top 10 of the 108 genes were: DNAJB11, RPL24, RPS3, PROS1, EIF4A2, ST6GAL1, RPS14, TBCE, EIF3I, and CCL2. Heritability for RFI was estimated to be 0.30. These results suggest that genetic selection for RFI has potential to improve the efficiency and, therefore, profitability of beef cattle production.