Genomewide association study of liver abscess in beef cattle

Authors: Keele, John; Kuehn, Larry; McDaneld, Tara; Tait Jr, Richard; Jones, Shuna; Keel, Brittney; Snelling, Warren

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/3/2015
Publication Date: 2/1/2016
Publication URL: http://handle.nal.usda.gov/10113/62014
Citation: Keele, J.W., Kuehn, L.A., McDaneld, T.G., Tait Jr, R.G., Jones, S., Keel, B.N., Snelling, W.M. 2016. Genomewide association study of liver abscess in beef cattle. Journal of Animal Science. 94(2):490-499.

Interpretive Summary: Liver abscesses affect 14% of cattle harvested at less than 20 months of age and 32% of cull dairy cows in the U.S. Cattle with liver abscesses have lower value carcasses, lighter carcasses, condemned livers, reduced feed intake, and reduced growth rate. Most liver abscesses result from excess acid in the rumen or forestomach resulting from too rapid fermentation of soluble carbohydrate by rumen microbes, followed by rumen lesions, bacterial invasion of the blood stream, and bacterial infections in the liver. We identified 35 regions on cattle chromosomes associated with incidence of liver abscess. Genes from associated chromosomal regions were previously known to affect acid balance in the digestive tract and circulation; liver repair following injury; movement of immune cells from the blood stream into infected tissues; and the ability of immune cells to engulf and destroy bacteria. These data are applicable to cattle finished on diets containing high levels of soluble carbohydrate which is the predominant way to feed cattle prior to harvesting in the U.S. These results will assist private and public sector geneticists to develop genetic evaluation systems that address incidence of liver abscesses. Sire selection to reduce liver abscess should benefit the beef industry through increased product value and reduced cost for producers and processing plants.

Technical Abstract: Fourteen percent of U.S. cattle slaughtered in 2011 had liver abscesses. As a result, these cattle have reduced carcass weight and poor carcass quality resulting in reduced value. Liver abscess can result from a common bacterial cause Fusobacterium necrophorum, which inhabits rumen lesions caused by acidosis, subsequently escapes into the blood stream, is filtered by the liver, and causes abscesses in the liver. Our aim was to identify SNP associated with liver abscess, which were collected at a beef processing plant. We collected samples of lung tissue instead of liver because lungs are a rich source of DNA and we had unrestricted access to lungs because of their low economic value in the U.S. We collected 2,304 lung samples from a beef processing plant; 1,152 from animals with liver abscess and 1,152 from animals without liver abscess. Tissue from pairs of animals, one with abscess and another without, were collected from near one another on the viscera table to ensure that pairs of phenotypically extreme animals came from the same lot. Within each phenotype (abscess or no abscess) cattle were pooled by slaughter sequence into 12 pools of 96 cattle for each phenotype for 24 total pools. Pools were constructed by equal volume of frozen lung tissue. The DNA was then extracted from the pooled lung tissue and the Bovine HD array (777,962 SNP) was run on all 24 pools; no technical replicates. Two traits were analyzed. The first trait, pooling allele frequency (PAF) was computed as red dye intensity divided by the total intensity or the sum of the intensities of the red and green dyes. The second trait was total intensity or the sum of intensities from red and green dyes. Both traits were weighted by the inverse of their respective genomic covariance matrices computed over all SNP across the genome. A false discovery rate (FDR) of < 5% was achieved for 15 SNP for PAF and 20 SNP for total intensity. Genes within 50 Kbp from significant SNP were in diverse pathways including maintainance of pH homeostasis in the gastrointestinal tract, immune defenses in the liver, migration of leukocytes from the blood into infected tissues, transport of glutamine into the kidney in response to acidosis to facilitate production of bicarbonate to increase pH, aggregate platelets to liver injury to facilitate liver repair, and facilitate axon guidance. Evidence from the 35 detected SNP associations combined with evidence of polygenic variation, indicate that there is adquate genetic variation in incidence rate of liver abscesses, which could be exploited to select sires for reduced susceptibility to subacute acidosis and associated liver abscess.