PSXII-18 Autophagy May Contribute to Variation in Residual Feed Intake in Hereford Cattle.

Residual feed intake (RFI) is heritable and variable among cattle. Understanding gene pathways and networks that regulate variation in the trait will aid in the selection of efficient animals. A total of 824 Hereford steers (RFI: -3.65 to 3.13 kg/d) from nine contemporary groups were genotyped with either the Illumina BovineHD or BovineSNP50 BeadChip assays. A genome-wide association analysis was used to identify significant SNP (P<0.05), which were used as proxies for each of the annotated genes in the UMD3.1 bovine reference genome assembly. Gene sets and leading edge genes (LEG) were identified with a SNP-based gene set enrichment analysis (GSEA-SNP) and upstream and master regulators influencing variation in RFI were determined using Ingenuity Pathway Analysis. One enriched gene set (endopeptidase activity, GO:0004175), with a normalized enrichment score>3.0) and 55 LEG, was identified by the GSEA-SNP. Endopeptidases cleave peptide bonds and may affect RFI through their important enzymatic roles in protein digestion. The autophagy related 7 (ATG7) gene was the most significant (P=1.9x10-10) master regulator associated with RFI. Significant (P<10–4) upstream regulators included collagen type XVIII alpha 1 chain (COL18A1), apolipoprotein E (APOE), interferon gamma (IFNG), and caspase 3 (CASP3). The COL18A1 gene produces a protein that makes collagen XVIII, found in basement membranes throughout the body, with anti-angiogenic and anti-tumor activities. The APOE gene functions in lipoprotein clearance and presentation of lipid antigens by antigen-presenting cells, while IFNG and CASP3 play key roles in autophagy and apoptosis. Autophagy is important for the maintenance of energy homeostasis, especially in response to nutrient availability. It is also involved with organ development and immune function. Gene set and pathway analyses suggest that the effects of autophagy on the maintenance of energy homeostasis, cellular and other functions, may contribute to variation in RFI in cattle.