Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis

M. L. Bermingham, S. C. Bishop, J. A. Woolliams, R. Pong-Wong, A. R. Allen, S. H. McBride, J. J. Ryder, D. M. Wright, R. A. Skuce, S. W. J. McDowell, E. J. Glass

Research output: Contribution to journalArticlepeer-review

Abstract

Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein-Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive vs skin test negative on multiple occasions, respectively. These animals were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 [times] 10-7) and myosin IIIB (MYO3B; P=5.4 [times] 10-6). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant in MYO3B. The results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.
Original languageEnglish
Pages (from-to)543-551
Number of pages9
JournalHeredity
Volume112
Issue number5
Early online date5 Feb 2014
DOIs
Publication statusPublished - May 2014

Keywords

  • genome-wide association study
  • bovine tuberculosis
  • novel resistance loci
  • MYCOBACTERIUM-BOVIS
  • CATTLE
  • GENES
  • SUSCEPTIBILITY
  • IRELAND
  • SURVEILLANCE
  • INFECTION
  • TRAITS
  • MAPS

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