A genome-wide association study for genetic susceptibility to Mycobacterium bovis infection in dairy cattle identifies a susceptibility QTL on chromosome 23.

BACKGROUND: Bovine tuberculosis (bTB) infection in cattle is a significant economic concern in many countries, with annual costs to the UK and Irish governments of approximately €190 million and €63 million, respectively, for bTB control. The existence of host additive and non-additive genetic components to bTB susceptibility has been established. METHODS: Two approaches i.e. single-SNP (single nucleotide polymorphism) regression and a Bayesian method were applied to genome-wide association studies (GWAS) using high-density SNP genotypes (n = 597,144 SNPs) from 841 dairy artificial insemination (AI) sires. Deregressed estimated breeding values for bTB susceptibility were used as the quantitative dependent variable. Network analysis was performed using the quantitative trait loci (QTL) that were identified as significant in the single-SNP regression and Bayesian analyses separately. In addition, an identity-by-descent analysis was performed on a subset of the most prolific sires in the dataset that showed contrasting prevalences of bTB infection in daughters. RESULTS: A significant QTL region was identified on BTA23 (P value >1 × 10(-5), Bayes factor >10) across all analyses. Sires with the minor allele (minor allele frequency = 0.136) for this QTL on BTA23 had estimated breeding values that conferred a greater susceptibility to bTB infection than those that were homozygous for the major allele. Imputation of the regions that flank this QTL on BTA23 to full sequence indicated that the most significant associations were located within introns of the FKBP5 gene. CONCLUSIONS: A genomic region on BTA23 that is strongly associated with host susceptibility to bTB infection was identified. This region contained FKBP5, a gene involved in the TNFα/NFκ-B signalling pathway, which is a major biological pathway associated with immune response. Although there is no study that validates this region in the literature, our approach represents one of the most powerful studies for the analysis of bTB susceptibility to date.

Variance components for susceptibility to Mycobacterium bovis infection in dairy and beef cattle.

BACKGROUND: Infection of livestock with bovine tuberculosis (bTB; Mycobacterium bovis) is of major economical concern in many countries; approximately 15 000 to 20 000 cattle are infected per year in Ireland. The objective of this study was to quantify the genetic variation for bTB susceptibility in Irish dairy and beef cattle. METHODS: A total of 105 914 cow, 56 904 heifer and 21 872 steer single intra-dermal comparative tuberculin test records (i.e., binary trait) collected from the years 2001 to 2010 from dairy and beef herds were included in the analysis. Only animal level data pertaining to periods of herd bTB infection were retained. Variance components for bTB were estimated using animal linear and threshold mixed models and co-variances were estimated using sire linear mixed models. RESULTS: Using a linear model, the heritability for susceptibility to bTB in the entire dataset was 0.11 and ranged from 0.08 (heifers in dairy herds) to 0.19 (heifers in beef herds) among the sub-populations investigated. Differences in susceptibility to bTB between breeds were clearly evident. Estimates of genetic correlations for bTB susceptibility between animal types (i.e., cows, heifers, steers) were all positive (0.10 to 0.64), yet different from one. Furthermore, genetic correlations for bTB susceptibility between environments that differed in herd prevalence of bTB ranged from 0.06 to 0.86 and were all different from one. CONCLUSIONS: Genetic trends for bTB susceptibility observed in this study suggest a slight increase in genetic susceptibility to bTB in recent years. Since bTB is of economic importance and because all animals are routinely tested at least once annually in Ireland and some other countries, the presence of genetic variation for bTB susceptibility suggests that bTB susceptibility should be included in a national breeding program to halt possible deterioration in genetic susceptibility to bTB infection.

Evidence for genetic variance in resistance to tuberculosis in Great Britain and Irish Holstein-Friesian populations.

BACKGROUND: Here, we jointly summarise scientific evidence for genetic variation in resistance to infection with Mycobacterium bovis, the primary agent of bovine tuberculosis (TB), provided by two recent and separate studies of Holstein-Friesian dairy cow populations in Great Britain (GB) and Ireland. METHODS: The studies quantified genetic variation within archived data from field and abattoir surveillance control programmes within each country. These data included results from the single intradermal comparative tuberculin test (SICTT), abattoir inspection for TB lesions and laboratory confirmation of disease status. Threshold animal models were used to estimate variance components for responsiveness to the SICTT and abattoir confirmed M. bovis infection. The link functions between the observed 0/1 scale and the liability scale were the complementary log-log in the GB, and logit link function in the Irish population. RESULTS AND DISCUSSION: The estimated heritability of susceptibility to TB, as judged by responsiveness to the SICTT, was 0.16 (0.012) and 0.14 (0.025) in the GB and Irish populations, respectively. For abattoir or laboratory confirmation of infection, estimates were 0.18 (0.044) and 0.18 (0.041) from the GB and the Irish populations, respectively. CONCLUSIONS: Estimates were all significantly different from zero and indicate that exploitable variation exists among GB and Irish Holstein Friesian dairy cows for resistance to TB. Epidemiological analysis suggests that factors such as variation in exposure or imperfect sensitivity and specificity would have resulted in underestimation of the true values.