Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows
Date
2017-06-24
Journal Title
Journal ISSN
Volume Title
Publisher
BMC
Abstract
Background: Susceptibility to Mycobacterium bovis infection in cattle is governed in part by host genetics.
However, cattle diagnosed as infected with M. bovis display varying signs of pathology. The variation in host
response to infection could represent a continuum since time of exposure or distinct outcomes due to differing
pathogen handling. The relationships between host genetics and variation in host response and pathological
sequelae following M. bovis infection were explored by genotyping 1966 Holstein-Friesian dairy cows at 538,231
SNPs with three distinct phenotypes. These were: single intradermal cervical comparative tuberculin (SICCT) test
positives with visible lesions (VLs), SICCT-positives with undetected visible lesions (NVLs) and matched controls
SICCT-negative on multiple occasions.
Results: Regional heritability mapping identified three loci associated with the NVL phenotype on chromosomes
17, 22 and 23, distinct to the region on chromosome 13 associated with the VL phenotype. The region on
chromosome 23 was at genome-wide significance and candidate genes overlapping the mapped window included
members of the bovine leukocyte antigen class IIb region, a complex known for its role in immunity and disease
resistance. Chromosome heritability analysis attributed variance to six and thirteen chromosomes for the VL and
NVL phenotypes, respectively, and four of these chromosomes were found to explain a proportion of the
phenotypic variation for both the VL and NVL phenotype. By grouping the M. bovis outcomes (VLs and NVLs)
variance was attributed to nine chromosomes. When contrasting the two M. bovis infection outcomes (VLs vs NVLs)
nine chromosomes were found to harbour heritable variation. Regardless of the case phenotype under
investigation, chromosome heritability did not exceed 8% indicating that the genetic control of bTB resistance
consists of variants of small to moderate effect situated across many chromosomes of the bovine genome.
Conclusions: These findings suggest the host genetics of M. bovis infection outcomes is governed by distinct and
overlapping genetic variants. Thus, variation in the pathology of M. bovis infected cattle may be partly genetically
determined and indicative of different host responses or pathogen handling. There may be at least three distinct
outcomes following M. bovis exposure in dairy cattle: resistance to infection, infection resulting in pathology or no
detectable pathology
Description
Publication history: Accepted - 31 May 2017; Published online - 24 June 2017.
item.page.type
Article
item.page.format
Keywords
Citation
Wilkinson, S., Bishop, S. C., Allen, A. R., McBride, S. H., Skuce, R. A., Bermingham, M., Woolliams, J. A. and Glass, E. J. (2017) ‘Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows’, BMC Genomics, 18(1). doi: 10.1186/s12864-017-3836-x.