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PSXII-19 Gene sets and pathways associated with residual feed intake in Angus steers.

ABSTRACT: Abstract Although residual feed intake (RFI) is a moderately heritable trait that can be used as a selection tool, little is known about gene pathways and networks that affect it. Angus steers (n=1,460) from 72 contemporary groups (RFI: -6.44 to 7.52 kg/d) were genotyped with Illumina BovineHD or BovineSNP50 BeadChip assays. Significant SNP (P<0.05), identified by a genome-wide association analysis on RFI, were used as proxies for each of the annotated genes in the UMD3.1 bovine reference genome assembly. A gene set enrichment analysis-SNP was performed to identify gene sets and leading edge genes (LEG) and a network analysis was conducted to identify upstream and master regulators influencing RFI. Three enriched gene sets (normalized enrichment score>3.0) related to energy production and efficiency of energy usage (cellular respiration, GO:0045333, 20 LEG; Reactome respiratory electron transport, R-HSA-611105, 12 LEG; respiratory chain, GO:0070469, 12 LEG) were identified, corroborating evidence from RFI studies with cattle and other species. Additional enriched gene sets were synaptic vesicle (GO:0008021, 16 LEG), cell-cell junction (GO:0005911, 55 LEG), and protein localization to plasma membrane (GO:0072659, 20 LEG). Mediator complex subunit 30 (MED30) and RPTOR independent companion of MTOR complex 2 (RICTOR) were the most significant (P<10-10) upstream regulators. Part of the Mediator complex, MED30 plays a key role in transcription regulation and mediates lipid biosynthesis while RICTOR is a component of the mTOR complex, which regulates mitochondrial metabolism. Thyroid stimulating hormone receptor (TSHR), part of the hypothalamus-pituitary-thyroid axis that is essential for growth and metabolism and Ras homolog enriched in brain like 1 (RHEBL1), a gene that activates the mTOR complex in the brain, were the two most significant (P<10–14) master regulators. Gene set and pathway analyses suggest that biological processes related to energy metabolism and mitochondrial function play important roles in controlling RFI in cattle.

SUBMITTER: Michal J

PROVIDER: S-EPMC6285512 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Project description:Growing ruminants maintained under dietary restriction for extended periods will exhibit compensatory growth when reverted to ad libitum feeding. This period of compensatory growth is associated with increased feed efficiency, lower basal energy requirements, and changes in circulating concentrations of metabolic hormones. To identify genetic mechanisms contributing to these physiological changes, 8 month-old steers were fed either ad libitum (control; n = 6) or 60-70% of intake of control animals (feed-restricted; n=6) for a period of 12 weeks. All steers were then fed ad libitum for the remaining 8 weeks of the experiment (realimentation period). Liver was biopsied from each animal at days -14, +1 and +14 relative to realimentation for RNA extraction and gene expression analysis by microarray hybridization. Steers were assigned randomly to one of two treatment groups, control or feed-restricted, and housed indoors in individual pens. Steers were acclimated to their pens for 5 d prior to starting the experimental treatments. Feed was offered once daily between 0630 and 0930 and orts from the previous day's feeding were collected and weighed to estimate actual intake. Control animals were fed ad libitum throughout the 20-wk experimental period. Feed-restricted steers were offered 60-70% of intake of control animals for 12 wks to target a limited rate of gain of approximately 0.5 kg/d. Restricted steers were then fed ad libitum for the remaining 8 wks of the experiment (realimentation period). During the first 3 d of realimentation, feed offered to both treatment groups was divided into two equal rations to gradually adjust restricted animals to full intake. Water was offered ad libitum throughout the experimental period. Approximately 200 mg of liver tissue was collected from each steer by needle biopsy using a Tru-Cut biopsy needle at -14, +1, +14 d relative to realimentation. Liver samples were immediately frozen in liquid nitrogen and stored at -80C until RNA isolation. Total RNA was isolated from 36 liver samples using TRIZOL Reagent (Invitrogen Corp., Carlsbad, CA). Samples were DNase-treated using the TURBO DNA-free kit (Ambion, Inc., Austin, TX) according to manufacturerâ??s instructions, followed by column purification using the RNeasy Mini Kit (Qiagen, Valencia, CA). Quality and concentration of RNA were assessed using a 2100 Bioanlayzer (Agilent Technologies, Palo Alto, CA) and ND-1000 spectrophotometer (NanoDrop Technologies, Wilmington, DE). Probe labeling, hybridizations of probes to the oligo microarray, and array scanning were performed by the Roche NimbleGen Systems, Inc. Microarray Core Facility in Reykjavik, Iceland according to standard procedures (Madison, WI; http://www.nimblegen.com).

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PSXII-19 Gene sets and pathways associated with residual feed intake in Angus steers.

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