Association of SNPs related to Johne’s disease with Holstein bulls EBVs for milk ELISA test scores
S. Mallikarjunappa, F. S. Schenkel, L. F. Brito, N. Bissonnette, K. G. Meade, F. Miglior, J. Chesnais, M. Lohuis, and N. A. Karrow. 2019. Association of SNPs related to Johne’s disease with Holstein bulls EBVs for milk ELISA test scores. 37th International Society for Animal Genetics Conference, Lleida, Spain, July 7-12.
Plain language summary
Johne's disease (JD) is a contagious and incurable disease caused by Mycobacterium avium subsp. paratuberculosis (MAP). Since there are currently no effective vaccines or treatment options available to control JD, genetic selection of potentially resistant individuals is being considered as a complementary strategy to decrease the incidence of JD in Canadian dairy herds. To make a genetic selection, we must first identify in the genes of cows susceptible to MAP infection variations that we want to eliminate from the population. Many variations associated with infection have been reported in the literature. The main objective of this study was to validate these previously identified variations by testing their effect on the offspring of Holstein bulls by estimating the breeding value (EBV) using data obtained from milk, namely by the presence of antibodies against MAP in milk. Although this is an indirect indicator of MAP infection status in cattle, the analysis identified three variations located on chromosomes 16, 23 and 26. Using tools additional genetic (quasi-likelihood analysis and regression analysis), four variations were identified, including two with both approaches and the other two located on chromosomes 9 and 16. In conclusion, the results of this study validate the association of known variations with MAP infection status in the Canadian Holstein breed and underline the need to further study the impact of these variations on gene activity.
Johne’s disease (JD) is a chronic intestinal inflammatory disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection in cattle. Since there are currently no vaccine and treatment options available to control JD, genetic selection may offer an alternative to enhance JD resistance. Numerous single nucleotide polymorphisms (SNPs) have been found to be associated with MAP infection status based on published genome-wide association and candidate gene studies. The objective of this study was to validate these JD SNPs by testing their association with Canadian Holstein bulls’ estimated breeding values (EBVs). A total of 500 bulls were classified into high and low antibody groups (n=250 in each group) based on their EBVs for milk ELISA test scores, an indirect indicator of MAP infection status in cattle. Both groups were then genotyped using a customized SNP panel comprising 155 of the most prominent JD SNPs reported in the literature, including studies using phenotypes other than milk ELISA to define the case-control populations. General Quasi Likelihood Scoring (GQLS) genome-wide association analysis based on logistic regression was used to carry out the validation using SNP1101 software. Three SNPs, rs41810662, rs41617133 and rs110225854, located on Bos taurus autosome (BTA) 16, 23 and 26, respectively, were confirmed as significantly associated with Canadian Holstein bulls’ EBVs for MAP infection status (FDR < 0.01). These findings highlight the need to further investigate the genomic regions harboring these SNPs. Since JD is a polygenic disease, where the accurate phenotyping of infected, resistant and disease-free animals remains difficult, the use of JD associated SNPs in a selective breeding program to increase resistance to MAP infection should be preceded by validation studies, preferably in independent dairy cattle populations.