|Tait Jr, Richard|
|Smith, Timothy - Tim|
|King, David - Andy|
Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/1/2015
Publication Date: 3/1/2015
Citation: Keele, J.W., Kuehn, L.A., McDaneld, T.G., Tait Jr., R.G., Jones, S., Smith, T.P., Shackelford, S.D., King, D.A., Wheeler, T.L., Lindholm-Perry, A.K., McNeel, A.K. 2015. Genomewide association study of lung lesions in cattle using sample pooling. Journal of Animal Science. 93(3):956-964. DOI: 10.2527/jas.2014-8492.
Interpretive Summary: Bovine respiratory disease complex is the most common reason for antibiotic treatment in feedlot cattle and costs the industry $1 billion per year. It is common for cattle that experience bovine respiratory disease complex during feeding to still have lung lesions present at harvest. Through a case-control study for lung lesion presence or absence, we performed a genome wide genetic association study that identified 7 single nucleotide polymorphisms with very strong associations to lung lesion presence. Five of these single nucleotide polymorphisms are near genes involved with lung development and repair mechanisms. Scientists are likely to investigate these genes and their polymorphisms for their roles in bovine respiratory disease incidence and lung tissue repair. This information may lead to new treatments for bovine respiratory disease in cattle. Additionally, these single nucleotide polymorphisms may be included in genetic tests available to cattle producers for selecting cattle less susceptible to bovine respiratory disease complex.
Technical Abstract: Bovine respiratory disease complex (BRDC) is the most expensive disease in beef cattle in the United States costing the industry at least $1 billion annually. BRDC causes damage to lung tissue resulting in persistent lung lesions observable at slaughter. Severe lung lesions at harvest have been associated with decreased pre-harvest ADG and increased clinical BRDC in the feedlot. Our objective was to identify SNP that are associated with severe lung lesions observed at harvest in feedlot cattle. We conducted a genome wide association study (GWAS) using a Case-Control design for severe lung lesions in fed cattle at slaughter using the Illumina Bovine HD array (~770,000 SNP) and sample pooling. Lung samples were collected from 11,520 young cattle, a portion of which had not been treated with antibiotics (participating in a Natural marketing program), at a large, commercial beef processing plant in central Nebraska. Lung samples with lesions (cases) and healthy lungs (controls) were collected when both phenotypes were in close proximity on the viscera (offal) table. We constructed 60 case and 60 control pools with 96 animals per pool. Pools were constructed by sampling sequence to ensure that Case and Control pool pairs were matched by proximity of the processing line. The Bovine HD array (770K SNP) was run on all pools. Seven SNP on BTA 3, 7, 9, 11, 14, and 15 were significant at the genome wide experiment wise error rate of 5 % (P </_ 1.49 × 10**-7). Eighty-four SNP on 28 chromosomes achieved a false discovery rate (FDR) of 5 % (P </_ 5.47 × 10**-6). Significant SNP were near (+/- 100 Kb) genes involved in tissue repair and regeneration, tumor suppression, cell proliferation, apoptosis, control of organ size, and immunity. Based on 84 significantly associated SNP in or near a collection of genes with diverse function on 28 chromosomes, we conclude that the genomic footprint of lung lesions is complex. A complex genomic footprint (genes and regulatory elements that affect the trait) is consistent with what is known about the cause of the disease; complex interactions among multiple viral and bacterial pathogens along with several environmental factors including dust, commingling, transportation and stress. Characterization of sequence variation near significant SNP will enable accurate and cost effective genome-enhanced genetic evaluations for BRDC resistance in AI bulls and seed stock populations.