title: A genome-wide association study for genetic susceptibility to Mycobacterium bovis infection in dairy cattle identifies a susceptibility QTL on chromosome 23.
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.
authors.affiliation: Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland. irichard@tcd.ie.|Animal and Grassland Research and Innovation Centre, Teagasc, Moorepark, Fermoy, Co. Cork, Ireland. irichard@tcd.ie.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Richardson
authors.affiliation: Animal and Grassland Research and Innovation Centre, Teagasc, Moorepark, Fermoy, Co. Cork, Ireland. Donagh.berry@teagasc.ie.
authors.forename: Donagh P
authors.initials: DP
authors.lastname: Berry
authors.affiliation: Animal and Bioscience Research Department, Animal and Grassland Research and Innovation Centre, Teagasc, Grange, Co. Meath, Ireland. heather.wiencko@equinome.com.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Wiencko
authors.affiliation: UCD Centre for Veterinary Epidemiology and Risk Analysis, UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland. isabella.higgins@ucd.ie.
authors.forename: Isabella M
authors.initials: IM
authors.lastname: Higgins
authors.affiliation: UCD Centre for Veterinary Epidemiology and Risk Analysis, UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland. simon.more@ucd.ie.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: More
authors.affiliation: Irish Cattle Breeding Federation, Bandon, Co. Cork, Ireland. jmcclure@icbf.com.
authors.forename: Jennifer
authors.initials: J
authors.lastname: McClure
authors.affiliation: Animal and Bioscience Research Department, Animal and Grassland Research and Innovation Centre, Teagasc, Grange, Co. Meath, Ireland. david.lynn@sahmri.com.|South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA, 5000, Australia. david.lynn@sahmri.com.|School of Medicine, Flinders University, Bedford Park, SA, 5042, Australia. david.lynn@sahmri.com.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lynn
authors.affiliation: Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland. DBRADLEY@tcd.ie.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bradley
mesh_terms: D000483:Alleles; D000818:Animals; D001499:Bayes Theorem; D001947:Breeding; D002417:Cattle; D033481:Chromosomes, Mammalian; D003612:Dairying; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000662:veterinary*; D005838:Genotype; D007494:Ireland; D008297:Male; D009163:Mycobacterium bovis / Q000302:isolation & purification; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D014380:Tuberculosis, Bovine / Q000235:genetics* / Q000382:microbiology; D006113:United Kingdom