0286 Identification of causal variants underlying pathogen susceptibility and translation to genetic improvement. (1st October 2016)

• Record Type: Journal Article
• Authors: Taylor, J. F.; Neibergs, H. L.; Seabury, C. M.; Vaneenennaam, A.; Decker, J. E.; Hoff, J. L.; Tizioto, P. C.; Womack, J. E.; Schnabel, R. D.
• Is Part Of: Journal of animal science. Volume 94(2016)Supplement 5
• Page Start: 135
• Page End: 136
• Publication Date: 2016-10-01
• Subjects: BRD -- GWAS -- causal variants -- estimated breeding values; Livestock -- Periodicals; Livestock; Electronic journals; Periodicals; 636.005
• DOI: 10.2527/jam2016-0286
• Languages: English
• ISSNs: 0021-8812

Abstract

Abstract: We have developed populations of 2781 preweaned Holstein calves (CA and NM) and 1862 Angus, Red Angus, Taurine Crossbred, Charolais and Hereford heifers and steers (WA and CO) that are approximately equally represented as cases or controls that are being used to train models for the prediction of additive genetic risk of Bovine Respiratory Disease (BRD). Analyzing BovineHD genotypes for these populations revealed heritabilities for BRD risk in the range from 20–23% and revealed numerous large effect QTL, many of which are located in genomic regions that also harbor genes that are differentially expressed between Angus × Hereford controls and animals challenged with single pathogens of the BRD Complex. To enable selection for increased resistance to the pathogens responsible for BRD, we seek to develop estimates of genetic merit that are robust to the breed composition of the tested animals and to the extent of their relatedness to these training populations. To accomplish this requires the identification of the causal variants that have a large effect on risk of BRD that were detected in Genome-Wide Association Analyses (GWAA). The strategy that we have followed involves the development of a functional variant assay known as the GGP-F250 that includes variants likely to alter the function of proteins through frameshifts, amino acid substitutions or altering the sequences of 5' and 3' untranslated regions. Variant discovery was performed using whole genome sequences (WGSs) for 262 taurines and RNA sequence data for 153 taurine animals. Variants were validated using 1000 Bull Genomes project data for 1147 sequenced animals and WGS data on 35 indicine or indicine × taurine composite animals. Holstein training population animals have been genotyped with this assay and the combined data have been imputed to WGS variation (∼11M variants with minor allele frequency > 5%) for the purpose of performing GWAA. The beef populations are likewise being imputed to WGS, and we seek to identify variants that are consistently associated with risk of BRD across populations for which the direction of allele effects is conserved across populations. These variants will be migrated to assays commercialized by Zoetis and GeneSeek that are routinely utilized by the beef and dairy industries to enable the translation of project results. This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2011–68004–30367 from the USDA National Institute of Food and Agriculture.