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Interleukin-12 (IL-12) and interleukin-23 (IL-23) are proinflammatory cytokines produced by macrophages and dendritic cells in response to infection with intracellular pathogens. The IL-12 receptor (IL-12R) is a heterodimer composed of 2 subunits, β1 and β2. The IL-23 receptor (IL-23R) is a heterodimer composed of the IL-12Rβ1 subunit and a unique IL-23R subunit. Given the importance of IL-12 and IL-23 for modulating inflammation and the host immune response, the IL-12 and IL-23 receptor genes may be suitable candidate genes for studying disease resistance in dairy cattle. We hypothesize that single nucleotide polymorphisms (SNP) exist within these genes and that they contribute to variation in health and production traits in dairy cattle. To investigate this, a selective DNA pool was constructed using bull semen based on the estimated breeding values for somatic cell score (SCS), an indicator trait used to achieve genetic improvement for resistance to mastitis. Gene segments were amplified from this pool by PCR and the amplicons were sequenced to reveal SNP. A total of 10 SNP, including 2 in IL-12Rβ1, 5 in IL-12Rβ2, and 3 in IL-23R were identified. The SNP (n=5) were found in the 5' untranslated region (UTR) putative promoter regions of the genes, and SNP IL-23R c.1714A>C was a nonsynonymous SNP. Canadian Holstein bulls (n=492) were genotyped using Sequenom MassARRAY (Sequenom Inc., San Diego, CA). No association was found with SCS based on bull deregressed estimated breeding values for SCS; however, associations of SNP in the IL-12Rβ2 gene (c.-511A>G, c.87A>G, c.2957A>C) were found with milk and protein yield. Further investigation will be required to elucidate the biological and practical relevance of these SNP.

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Mycobacterium avium ssp. paratuberculosis (MAP) infection causes a chronic granulomatous inflammatory condition of the bovine gut that is characterized by diarrhea, progressive weight loss, and emaciation, and ultimately leads to loss in productivity and profitability of dairy operations. The host cytokine machinery is known to play an important role in protecting against MAP infection. Therefore, the goal of the present study was to assess whether polymorphisms in candidate genes encoding important cytokines and cytokine receptors are associated with MAP infection status of dairy cattle. MAP infection status was evaluated based on serum and milk enzyme-linked immunosorbent assays (ELISAs) for MAP-specific antibodies. Twenty previously reported polymorphisms in genes encoding bovine interferon gamma (IFNG), IFNGR1, IFNGR2, IL22, IL22RA1, IL12RB1, IL12RB2, and IL23R were genotyped in a resource population of 446 dairy Holsteins with known MAP infection status, and logistic regression was used to assess the statistical association with a binomial MAP infection status phenotype. Four SNPs in IFNGR2, IL12RB1, IL12RB2, and IL23R were found to be associated with the MAP infection status of the resource population. These results underscore the importance of cytokines and their receptors in conferring protection against MAP infection and warrant further functional characterization of these associations.