Downey-Slinker, Erika Diane (2016-05). Studies of Immunogenetic Variation in Cattle. Doctoral Dissertation.
Genetic selection for animal health and disease resistance has been limited, likely due to the challenges of performing controlled studies with an industry relevant phenotype. Studies in large populations of animals of unknown relationship pose challenges for genome wide association studies of disease resistance. The aims of this project were to characterize variation in the bovine major histocompatibility complex (BoLA), a specific region of the bovine genome known be critical for development of immune response, and then investigate individual variation in host immunity to a specific viral pathogen of cattle, bovine viral diarrhea virus (BVDV).
Cattle "homozygous" for BoLA were identified from approximately 2,000 head of Holstein calves in large genome wide association studies. Cattle were genotyped on the Illumina BovineHD SNP chip and PHASED for the characterization of BoLA haplotypes. Among 160 "homozygous" animals, we identified 38 different haplotype groups. The 38 haplotype groups maintained the structure predicted by earlier studies that identified 50K SNP haplotypes, but demonstrated that more diversity is present among these 38 BoLA haplotype groups than was indicated by the 50K haplotypes. Among the 1,221 SNPs genotyped on the HD chip were 230 SNPs with no calls in at least one of the 160 homozygous animals. The no call SNPs are located predominately in regions predicted to contain copy number variation, and no call SNPs appear to likely mark regions of polymorphic structural variation otherwise undetected in the SNP defined haplotypes. This structural variation may be important for future genome association studies.
Cattle diseases are often difficult to diagnose due to presentation with different disease phenotypes, ranging from subclinical to lethal. Likewise, immune response to vaccination is also variable and may be related to individual differences in disease susceptibilities. To evaluate individualized response to BVDV vaccination, we evaluated protection afforded by commercial vaccines against a BVDV challenge. The results from the BVDV challenge study indicate that measuring antibody titer as a response to BVDV vaccination may not be predictive of a protective immune response. Rectal temperature alone for health classification missed up to 50% of animals with subclinical disease.
Variation in host immunity appears to underlie the response to pathogens and likely to vaccination as well. Host differences in immunity between Bos indicus and Bos taurus cattle were evaluated subsequent to BVDV vaccination. Differences in baseline immune cell counts were observed. Indicine cattle had higher white blood cell counts primarily influenced by the 2-fold higher neutrophil levels. Response to vaccination was primarily observed as an innate immune response with an increase in neutrophils. The largest change was in neutrophil response observed in the taurine calves. Immunosuppression from the modified live vaccination was greater in the indicine calves compared to taurine calves. However, a combination of vaccination protocols appear to mitigate the immunosuppression observed in the indicine cattle.