Genetic Regulation of Immune Responses in Holstein Dairy Cows across Canada
Diseases that affect dairy cattle have serious economic and animal welfare implications. The inclusion of immune response (IR) traits in breeding indices has been suggested to improve inherent animal health, and decrease the use of antimicrobials. The objectives of this research were to (1) evaluate cell-mediated (CMIR) and antibody-mediated immune responses (AMIR) on 680 Holstein cows from 58 herds across Canada, (2) estimate genetic parameters of these traits (3) examine the associations with routinely evaluated traits as well as the incidence of mastitis, (4) evaluate the correlation of natural and specific antibody and (5) perform a genome-wide association study (GWAS) to determine genetic markers associated with high or low IR. In collaboration with the Canadian Bovine Mastitis Research Network cows were immunized with both a type 1 and type 2 test antigen to stimulate CMIR and AMIR, respectively. A cutaneous delayed-type hypersensitivity test to the type 1 test antigen was used as an indicator of CMIR, and serum antibody (IgG1 and IgG2) to the type 2 test antigen as an indicator of AMIR. IR phenotypes varied significantly by cow, herd and region in Canada. Heritability estimates were moderate, 0.19 for CMIR and 0.16-0.43 for AMIR depending on time in the immunization protocol and antibody isotype. Beneficial associations between AMIR and some reproductive traits were found. Using estimated breeding values, cows were classified as high, average or low responders. High AMIR cows had significantly lower incidence rates of clinical mastitis compared to average and low cows. No difference was found when cows were classified based on CMIR. Natural antibody was not genetically correlated with specific antibody nor was it associated with mastitis. The GWAS found 198 genetic markers significantly associated with AMIR, with the majority on chromosome 23 where the major histocompatability complex is located. Other significant genes involved in IR include those associated with the complement system, interleukin 17 and tumor necrosis factor. This research confirms the benefit of identifying high IR cows and gives a glimpse of current IR profiles in Canadian Holsteins. This was the first GWAS for IR traits in dairy cattle and suggests it may be possible to include IR traits in genomic selection indices.