Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis

Abstract

Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein–Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive vs skin test negative on multiple occasions, respectively. These animals were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 × 10−7) and myosin IIIB (MYO3B; P=5.4 × 10−6). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant in MYO3B. The results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.

An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistance

“…The SNPs identified in the present study were consistent with findings previously published by Bermingham et al . (2014) using the same data but different statistical procedures.…”

“…All cases were positive for the single intradermal comparative cervical test (SICCT) and had bTB lesions confirmed by carcass inspection, culture and molecular tests (Bermingham et al . 2014). Controls were age‐matched with cases and selected from herds with higher disease prevalence to increase their probability of exposure to the pathogen (Bishop 2012).…”

“…CMDS revealed a secondary distinct cluster of 40 individuals, 39 of these from a single herd that included crossbreds, as had been observed previously (Bermingham et al . 2014). Therefore to address this, the analyses described below were repeated with and without this cluster.…”

“…To provide a check on consistency with the additive screen published by Bermingham et al . (2014), d k was replaced by x k in Model (Model 2), where x k is the vector of counts for locus k described above.…”

“…An alternative approach for selecting more resistant individuals is through identifying individual QTL that explain significant amounts of the genetic variance and exploiting this knowledge in marker‐assisted selection, which was examined for bTB resistance by Bermingham et al . (2014). Selection for disease resistance based on single QTL has previously been implemented successfully in aquaculture and livestock species: e.g.…”