Abstract
BackgroundThe significant social and economic loss as a result of bovine tuberculosis (bTB) presents a continuous challenge to cattle industries in the UK and worldwide. However, host genetic variation in cattle susceptibility to bTB provides an opportunity to select for resistant animals and further understand the genetic mechanisms underlying disease dynamics.MethodsThe present study identified genomic regions associated with susceptibility to bTB using genome-wide association (GWA), regional heritability mapping (RHM) and chromosome association approaches. Phenotypes comprised de-regressed estimated breeding values of 804 Holstein-Friesian sires and pertained to three bTB indicator traits: i) positive reactors to the skin test with positive post-mortem examination results (phenotype 1); ii) positive reactors to the skin test regardless of post-mortem examination results (phenotype 2) and iii) as in (ii) plus non-reactors and inconclusive reactors to the skin tests with positive post-mortem examination results (phenotype 3). Genotypes based on the 50 K SNP DNA array were available and a total of 34,874 SNPs remained per animal after quality control.ResultsThe estimated polygenic heritability for susceptibility to bTB was 0.26, 0.37 and 0.34 for phenotypes 1, 2 and 3, respectively. GWA analysis identified a putative SNP on Bos taurus autosomes (BTA) 2 associated with phenotype 1, and another on BTA 23 associated with phenotype 2. Genomic regions encompassing these SNPs were found to harbour potentially relevant annotated genes. RHM confirmed the effect of these genomic regions and identified new regions on BTA 18 for phenotype 1 and BTA 3 for phenotypes 2 and 3. Heritabilities of the genomic regions ranged between 0.05 and 0.08 across the three phenotypes. Chromosome association analysis indicated a major role of BTA 23 on susceptibility to bTB.ConclusionGenomic regions and candidate genes identified in the present study provide an opportunity to further understand pathways critical to cattle susceptibility to bTB and enhance genetic improvement programmes aiming at controlling and eradicating the disease.
Highlights
The significant social and economic loss as a result of bovine tuberculosis presents a continuous challenge to cattle industries in the UK and worldwide
genome-wide association (GWA) analysis Association between individual Single neucleotide polymorphism (SNP) and bovine tuberculosis (bTB) susceptibility traits are illustrated in the Manhattan plots in Fig. 1, with corresponding quantile-quantile plots in Additional file 3
The present study identified two additive SNPs in moderate linkage disequlibrium (LD) with neighbouring SNPs on Bos taurus autosomes (BTA) 2 and 23 that were significantly associated with different traits of susceptibility to bTB
Summary
The significant social and economic loss as a result of bovine tuberculosis (bTB) presents a continuous challenge to cattle industries in the UK and worldwide. In Great Britain, bTB control and eradication programme involves routine testing and compulsory slaughter of infected animals and cattle movement restrictions in the affected herds. When reaction to M. bovis tuberculin injection is estimated to be less than or equal to that to M. avium tuberculin injection the skin test is deemed negative. A positive skin test result, known as a ‘reactor,’ is asserted when the reaction to M. bovis tuberculin exceeds that to M. avium tuberculin by more than 4 mm. A breakdown (bTB incident) is declared once at least one reactor is discovered in a herd, prompting animal movement restrictions, suspension of the OTF status of the herd and testing of all animals in the herd at 60-day interval. Animals with a positive or two consecutive inconclusive skin tests are slaughtered and examined at the abbatoir for visible lesions of bTB in their organs. The breakdown remains ‘open’ and skin testing continues in the herd until two consecutive negative herd tests are obtained
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