Location: Animal Health GenomicsTitle: Association of ARRDC3 and NF1A genes with bovine congestive heart failure
|Heaton, Michael - Mike|
|BASSETT, ADAM - University Of Nebraska|
|CLARK, HALDEN - University Of Nebraska|
|CARLSON, JADEN - University Of Nebraska|
|PELSTER, MADELINE - University Of Nebraska|
|GROTELUESCHEN, DALE - University Of Nebraska|
|VANDER LEY, BRIAN - University Of Nebraska|
Submitted to: Plant and Animal Genome Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 12/1/2019
Publication Date: 1/13/2020
Citation: Heaton, M.P., Harhay, G.P., Bassett, A.S., Clark, H.J., Carlson, J.M., Smith, H.R., Pelster, M.C., Workman, A.M., Grotelueschen, D.M., Vander Ley, B.L. 2020. Association of ARRDC3 and NF1A genes with bovine congestive heart failure. In: Plant and Animal Genome Conference Proceedings, January 11-15, 2020, San Diego, California. PE0326.
Technical Abstract: Background: Bovine congestive heart failure (BCHF) has become increasingly prevalent in feedlot cattle in the Western Great Plains of North America with up to 7% mortality in disease outbreaks. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. No candidate genes are presently associated with BCHF, and thus, our aim was to search genome-wide for genetic risk factors in feedlot cattle. Methods: Samples of 102 clinical BCHF cases and 102 unaffected matched penmates were used in a genome-wide association study (GWAS) with 777,962 single nucleotide polymorphisms (SNPs). The paired nominal data were analyzed with McNemar’s test. Results: Analyses of 563,042 filtered SNPs revealed more than 15 genomic regions highly associated with BCHF. Regions with the strongest association included the arresting domain-containing 3 protein (ARRDC3) and nuclear factor IA (NFIA) genes. A missense mutation in exon 4 of ARRDC3 (C182Y), and SNPs in intron 5 of NFIA had the best statistical support for association (McNemar's Chi-square > 20). Animals with either or both the ARRDC3 or NFIA risk factors, were approximately 7- and 15-fold more likely to have BCHF compared to those without (p-value < 10-10 for both risks present). A two-SNP genotyping test for ARRDC3 and NFIA risk factors was used to test an independent cohort of feedlot cattle with end-stage heart failure and similar associations with disease were observed. Conclusions: A matched case-control GWAS identified major genes associated with BCHF in feedlot cattle. Although the roles of these genes in disease pathogenesis are unknown, their discovery facilitates classifying animals by genetic risk for heart failure and will allow producers to make informed decisions for selective breeding and animal health management.