A genome-wide association study of immune response traits in Canadian Holstein cattle

Abstract

Background: Breeding for enhanced immune response (IR) has been suggested as a tool to improve inherent animal health. Dairy cows with superior antibody-mediated (AMIR) and cell-mediated immune responses (CMIR) have been demonstrated to have a lower occurrence of many diseases including mastitis. Adaptive immune response traits are heritable, and it is, therefore, possible to breed for improved IR, decreasing the occurrence of disease. The objective of this study was to perform genome-wide association studies to determine differences in genetic profiles among Holstein cows classified as High or Low for AMIR and CMIR. From a total of 680 cows with immune response phenotypes, 163 cows for AMIR (81 High and 82 Low) and 140 for CMIR (75 High and 65 Low) were selectively genotyped using the Illumina Bovine SNP50 BeadChip. Results were validated using an unrelated population of 164 Holstein bulls IR phenotyped for AMIR and 146 for CMIR.

Results: A generalized quasi likelihood score method was used to determine single nucleotide polymorphisms (SNP) and chromosomal regions associated with immune response. After applying a 5% chromosomal false discovery rate, 186 SNPs were significantly associated with AMIR. The majority (93%) of significant markers were on chromosome 23, with a similar peak found in the bull population. For CMIR, 21 SNP markers remained significant. Candidate genes within 250,000 base pairs of significant SNPs were identified to determine biological pathways associated with AMIR and CMIR. Various pathways were identified, including the antigen processing and presentation pathway, important in host defense. Candidate genes included those within the bovine Major Histocompatability Complex such as BoLA-DQ, BoLA-DR and the non-classical BoLA-NC1 for AMIR and BoLA-DQ for CMIR, the complement system including C2 and C4 for AMIR and C1q for CMIR, and cytokines including IL-17A, IL17F for AMIR and IL-17RA for CMIR and tumor necrosis factor for both AMIR and CMIR. Additional genes associated with CMIR included galectins 1, 2 and 3, BCL2 and β-defensin.

Conclusions: The significant genetic variation associated with AMIR and CMIR in this study may imply feasibility to include immune response in genomic breeding indices as an approach to improve inherent animal health.

Figure 1

Manhattan plot for antibody-mediated immune response (AMIR) in Holstein cows. The x-axis is the position of each SNP on the bovine chromosomes and the y-axis is the –log₁₀ P. The red and blue lines indicate chromosome-wise 5% and 1% false discovery rate, respectively.

Figure 2

Manhattan plot for antibody-mediated immune response (AMIR) SNPs on chromosome 23 of Holstein cows. The x-axis is the position of each SNP on the bovine chromosome and the y-axis is the –log₁₀ P. The lines indicate chromosome-wise false discovery rate (FDR).

Figure 3

Manhattan plot for the cell-mediated immune response (CMIR) in Holstein cows. The x-axis is the position of each SNP on the bovine chromosomes and the y-axis is the –log₁₀ P. The red and blue lines indicate chromosome-wise 5% and 1% false discovery rate, respectively.

Figure 4

Manhattan plot for the cell-mediated immune response (CMIR) SNPs on chromosome 23 of Holstein cattle. The x-axis is the position of each SNP on the bovine chromosome and the y-axis is the –log₁₀ P. The lines indicate chromosome-wise false discovery rate (FDR).

Figure 5

Manhattan plot for the antibody-mediated immune response in Holstein bulls. The x-axis is the position of each SNP on the bovine chromosomes and the y-axis is the –log₁₀ P. The red and blue lines indicate chromosome-wise 5% and 1% false discovery rate, respectively.

Figure 6

Manhattan plot for the cell-mediated immune response in Holstein bulls. The x-axis is the position of each SNP on the bovine chromosomes and the y-axis is the –log₁₀ P. The red and blue lines indicate chromosome-wise 5% and 1% false discovery rate, respectively.