Genetic Variation in the Bovine MHC is Associated with Subclinical Leukopenia in Vaccinated Angus-Nellore Steers

Bovine viral diarrhea (BVD) is an internationally relevant disease that affects both dairy and beef cattle. This study evaluated the immunological response to a type 1b BVDV challenge in vaccinated versus non-vaccinated yearling Angus-Nellore steers and subsequently tested for genetic associations between leukopenia and immune related SNPs on a customized Illumina GoldenGate SNP chip. Animals that express subclinical leukopenia have reduced performance in the feedlot but are not typically diagnosed or treated. Vaccinated steers were 15% less likely to show subclinical symptoms when challenged with the 1b strain of BVDV when compared to non-vaccinated steers. Leukopenia phenotypes and the platelet/lymphocyte decline were tested for associations with SNPs on regions of chromosomes 2, 18, and 23 previously identified as associated with immune response. Bovine SNP rs133597460 was significantly associated (P < 0.01, Bonferroni adjusted) with lymphocyte decline post-challenge.  rs133597460 is located on chromosome 23, approximately 200 KB upstream of BoLA-DQB2. Epistatic interactions were tested for association with case/control leukopenia phenotypes using PLINK. An interaction between SNPs rs41641292 and rs110547095 was associated with reduced platelets and pyrexia in challenged steers. Both SNPs are located in intergenic regions of the BoLA class I region. A significant epistatic association was found among 10 pairs of SNPs associated with platelet and lymphocyte decline. The most significant interactions were observed between inducible T-cell co-stimulator (ICOS), on chromosome 2 and BoLA-DRB2, and between BoLA-DRA, and C23H6orf10, on chromosome 23.These findings indicate that subclinical illness may be controlled by genetic factors.