Abstract
BackgroundBovine tuberculosis is a significant veterinary and financial problem in many parts of the world. Although many factors influence infection and progression of the disease, there is a host genetic component and dissection of this may enlighten on the wider biology of host response to tuberculosis. However, a binary phenotype of presence/absence of infection presents a noisy signal for genomewide association study.Methodology/Principal FindingsWe calculated a composite phenotype of genetic merit for TB susceptibility based on disease incidence in daughters of elite sires used for artificial insemination in the Irish dairy herd. This robust measure was compared with 44,426 SNP genotypes in the most informative 307 subjects in a genome wide association analysis. Three SNPs in a 65 kb genomic region on BTA 22 were associated (i.e. p<10−5, peaking at position 59588069, p = 4.02×10−6) with tuberculosis susceptibility.Conclusions/SignificanceA genomic region on BTA 22 was suggestively associated with tuberculosis susceptibility; it contains the taurine transporter gene SLC6A6, or TauT, which is known to function in the immune system but has not previously been investigated for its role in tuberculosis infection.
Highlights
Bovine tuberculosis (TB) is a serious cattle disease, caused by infection with Mycobacterium bovis
After two rounds of quality control 44426 markers and 986 samples passed all criteria. 307 of these samples had informative Estimated breeding values (EBV) for TB susceptibility and only these were used in analysis of TB susceptibility
No outliers were identified by the Multi dimensional scaling (MDS) so all EBV informative samples were included in the genome wide analysis
Summary
Bovine tuberculosis (TB) is a serious cattle disease, caused by infection with Mycobacterium bovis. It costs an estimated $3 billion annually in global agricultural losses [1] and is the fourth most important livestock disease worldwide [2]. Knowledge of resistance to the disease in cattle may provide insights into the global medical problem of human tuberculosis, as the immune response of cattle to mycobacterial infection bears a closer resemblance to that in humans than it does in mice [7]. Many factors influence infection and progression of the disease, there is a host genetic component and dissection of this may enlighten on the wider biology of host response to tuberculosis. A binary phenotype of presence/absence of infection presents a noisy signal for genomewide association study
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