PSIII-3 Genes and functions associated with tolerance to fescue toxicosis in Angus cows

Abstract

Abstract The objective of this study was to identify differentially expressed genes (DEG) and functions associated with tolerance to fescue toxicosis (FT). Forty pregnant purebred Angus cows were selected based on their growth at two locations in North Carolina (Butner Beef Cattle Field Laboratory, BBFCL; Upper Piedmont Research Station, UPRS) and classified as either high tolerant (HT) or low tolerant (LT) to FT with 20 cows in each group balanced by location. Blood samples were collected on weeks 1, 5, 9, and 13 for RNA sequencing. Counts were analyzed using a negative binomial model including the effects of genetic group, location, time, all possible interactions of these effects, flow cell, covariate of RNA integrity number, and normalized library size as offset. Genotype-by-location-by-time interaction was evident with a high number (4,453) of DEG (q-value<0.1) between genetic groups on week 5 at UPRS compared to all other possible interactions. So further analyses were focused on week 5 at UPRS. The most significant upregulated genes in LT and HT animals were ENPP6 and MESP2, respectively, with log2 fold changes of 1.90 [95% confidence interval = 0.89, 2.92] q-value=0.005) and 0.91 [0.35, 1.47] (q-value=0.01), respectively. Other top 5 upregulated genes for HT animals were CTBS, CLDN19, SPDYC, HEYL, and SDC2, and for LT animals were OLIG1, IL13, ANXA13, ENSBTAG00000024188and CXCL13. Enrichment analysis (P < 0.05) showed that DEG between genetic groups have general functions, such as metabolic, biosynthetic, and catabolic processes, as well as DNA and RNA-related functions, such as translation, transcription, and repair. These findings helped characterizing the genetic basis of tolerance to FT in cattle. In addition, we identified genes that may serve as potential biomarkers for tolerance to FT