Genetic approaches to identify genomic regions associated with decreased susceptibility to bovine respiratory disease complex

Abstract

One approach to reducing losses from BRDC is the implementation of selection of cattle that are less likely to be affected by disease by the use of dairy predicted transmitting ability (PTA) or beef expected progeny differences (EPD) for susceptibility to BRDC. The PTAs or EPDs would be based on genotypes associated with animals less susceptible to disease and incorporated into commercial genotyping platforms for industry use. The discovery of quantitative trait loci (QTL) associated with BRDC susceptibility is the first step in implementing the selection of cattle for enhanced resistance to BRDC. Feedlot crossbred Bos taurus (n=408) heifers from Washington were used to illustrate how genetic approaches identify BRDC susceptibility QTL that will form the basis for selection of cattle with increased resistance to the disease. The crossbred cattle consisted of 234 cases and 174 controls as defined by the McGuirk Health scoring system. Cases and controls remained in the same pens together throughout the study. The incidence of BRDC in the feedlot was 2.5% over a 15-month period. The distinction between cases and controls was based on the McGuirk health scoring system with possible integer scores ranging between 0 and 12; calves with scores <4 were identified as controls and those with a score >5 were identified as a case. Of the 174 controls, 4 (1.7%) subsequently became ill with BRDC and were reclassified as a case. The mean health score was 9.44 ± 1.19 for cases and 2.36 ± 0.61 for controls. Deeppharyngeal and mid-nasal swabs were taken for bacteriology and virology diagnostics. Histophilus somni had the greatest difference in prevalence between cases and controls (odds ratio = 1.65, 95% confidence interval 1.05 - 2.58, p < 0.05) among the detected pathogens. A genome-wide association analysis (GWAA) and genomic heritability estimate was computed using Illumina BovineHD BeadChip genotypes. Heritability of susceptibility to BRDC was estimated at 37%. After correction for population stratification using 30 principal components, the genomic inflation factor was 1.02. Single nucleotide polymorphisms (SNPs) were filtered for low call rate (<90%), Hardy-Weinberg disequilibrium (p < 1x10^-50) and low minor allele frequency (<1%) which left 669,933 SNPs for the GWAA. Animals were also filtered for low genotyping call rate (<90%) leaving 220 cases and 164 controls. The GWAA identified 43 QTL (p < 5x10^-5) on 15 chromosomes. The identification of QTL associated with BRDC susceptibility is the first step towards implementing selection of cattle that are less likely to be affected by BRDC through the use of genomic PTAs or EPDs.