| Infectious disease can have a considerable impact on the dairy' industry worldwide. Breeding livestock for disease resistance has been long sought as a means to reduce such impact; unfortunately, this approach has traditionally yielded little genetic gain. However, recent advances in genomic technologies teamed with an approach known as marker-assisted selection, have the potential to make these breeding goals a reality.;The use of genetic markers in a selective breeding program focusing to improve disease resistance will likely be of great importance in the near future. The current research emphasizes that it is necessary to functionally validate resultant genetic associations as they could be due to linkage disequilibrium with the true causal polymorphism. Furthermore, it has provided compelling evidence that SNPs in IL10RA and MIF should be considered as worthwhile candidates to reduce the susceptibility of dairy cattle to mastitis or Johne's disease.;The purpose of this study was to identify single nucleotide polymorphisms (SNPs), which are associated with the susceptibility of dairy cattle to mastitis and Johne's disease. The candidate genes interleukin-10 (IL10) and its receptor (IL10RA/B), transforming growth factor beta 1 (TGFB1) and its receptor (TGFBR1/1), macrophage migration inhibitory factor (MIF), and natural resistance-associated macrophage protein 1 (NRAMP1), were selected for SNP discovery based on their importance in modulating the innate inflammatory response to bacteria. Sixteen SNPs were identified in IL10 (n=2), IL10RA/B (n=6/2), TGFB1 (n=1), MIF (n=3) and NRAMP1 (n=2), which were subsequently genotyped in a sample population of Holstein bulls and cows. Genetic association analysis identified significant effects for SNPs in IL10RA with estimated breeding values for somatic cell score (SCS), an indicator trait for mastitis, and for SNPs in IL10RA and MIF with Mycobacterium avium ssp. paratuberculosis (MAP) infection status, an indicator trait for Johne's disease. Functional validation of SNPs in MIF using a dual luciferase reporter gene assay supported the observed genetic associations. Finally, comparison of gene expression profiles of peripheral blood mononuclear cells in healthy and MAP-infected Holstein and Jersey cows identified novel breed-specific differences as well as new candidates for future genetic association studies. |
