Type

Journal Article

Authors

Daniel G Bradley
David J Lynn
Jennifer McClure
Simon J. More
Isabella M. Higgins
Heather L Wiencko
Donagh P. Berry
Ian W. Richardson

Subjects

Veterinary

Topics
genetic association mycobacterium bovis bovine tuberculosis btb single snp regression bovine tuberculosis quantitative trait loci genome wide association studies genome wide association study susceptibility qtl dairy cattle

A genome-wide association study for genetic susceptibility to Mycobacterium bovis infection in dairy cattle identifies a susceptibility QTL on chromosome 23 (2016)

Abstract 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.
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Full list of authors on original publication

Daniel G Bradley, David J Lynn, Jennifer McClure, Simon J. More, Isabella M. Higgins, Heather L Wiencko, Donagh P. Berry, Ian W. Richardson

Experts in our system

1
Daniel Bradley
Trinity College Dublin
Total Publications: 80
 
2
David J Lynn
Teagasc
Total Publications: 36
 
3
Jennifer McClure
Teagasc
Total Publications: 5
 
4
S J More
University College Dublin
Total Publications: 171
 
5
Isabella M. Higgins
Teagasc
Total Publications: 13
 
6
Heather L Wiencko
Teagasc
Total Publications: 3
 
7
D P Berry
Teagasc
Total Publications: 215
 
8
Ian W. Richardson
Teagasc
Total Publications: 8