Genetic Markers Associated with Susceptibility to Bovine Respiratory Disease

Bovine respiratory disease complex (BRDC) is the most expensive disease afflicting the U.S. beef industry. Efforts to reduce the effects of this disease have had modest success likely due to the multi-factorial nature of the disease with environmental and managerial factors interacting with associated bacterial and viral agents. Previous work suggest a genetic component to animal susceptibility to BRDC; therefore the objective of this study was to identify DNA markers associated with incidence of BRDC in commercial feedlot cattle. Using a case/control strategy, DNA samples from 3,648 commercial feedlot animals were collected with half (n=1,824) having shown clinical signs of BRDC (i.e. cases) and the other half non-symptomatic controls sampled from the corresponding feedlot pen. A DNA pooling approach was used in the genome-wide association study. After extraction, a high density bovine marker array was run on 19 case and 19 control DNA pools of approximately 96 animals each. There were ~770,000 SNP with sufficient data quality for all 38 pools. Twelve SNP achieved a false discovery rate (FDR) of 5 % or less in the genome wide association analysis. There were 3 significant SNP on BTA11, 2 on BTAX and 1 each on BTA 1, 9, 18, 22, 24, 27, and 29. Three significant SNP were located in intergenic regions and 9 occurred within introns or exons of genes. Significant SNP resided within the introns of LOC100847501, HPCAL1, RSAD2, DNAAF3, CCD1798, and ATP7A; and exons of LOC510798 (missense) and LOC519208 (synonymous). The potential role of some of these genes in BRDC is suggested by literature. For instance, the RSAD2 transcript response to bacterial lipopolysaccharides has been reported to decrease in the presence of bovine viral diarrhea virus. In humans, mutations in DNAAF3 cause primary ciliary dyskinesia resulting in ineffective airway mucocilliary clearance and frequent respiratory infections in human infants. The ATP7A gene has been suggested to influence bactericidal activity in macrophages through its role in copper homeostatis. The results of this study indicate a genetic component to susceptibility to BRDC and encourage the development of DNA marker tests to aid in selection of animals less susceptible to BRDC.