Abstract
BackgroundBovine 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.MethodsTwo 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.ResultsA 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.ConclusionsA 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-016-0197-x) contains supplementary material, which is available to authorized users.
Highlights
Bovine tuberculosis 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
Its major allele A was associated with increased resistance to bTB infection, and homozygous animals for this allele had a mean estimated breeding values (EBV) of −0.099 (n = 378, SD = 0.1390), whereas homozygous animals for the minor allele (MAF = 0.33) had a mean EBV of −0.0120 (n = 105, SD = 0.2010)
Due to the likely polygenic nature of bTB susceptibility, several approaches applied to genome-wide association studies (GWAS) were conducted to identify novel associations that would otherwise not be identified by using a single-SNP approach
Summary
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. Bovine tuberculosis (bTB; caused by infection with Mycobacterium bovis) is an important infectious disease, that affects primarily cattle. It is an OIE (World Organisation for Animal Health) listed disease (https://www.oie.int), Richardson et al Genet Sel Evol (2016) 48:19. Both within-breed [5,6,7] and between-breed [5, 8] variation in susceptibility to bTB in dairy and beef cattle have been reported. Several single gene investigations for bTB-related traits have been reported and NRAMP1 (SLC11A) was identified as a susceptibility locus in both cattle and humans [22,23,24]
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