Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows

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dc.contributor.authorWilkinson, S.
dc.contributor.authorBishop, S.C.
dc.contributor.authorAllen, Adrian
dc.contributor.authorMcBride, S.H.
dc.contributor.authorSkuce, Robin
dc.contributor.authorBermingham, M.
dc.contributor.authorWoolliams, J.A.
dc.date.accessioned2021-07-28T14:53:12Z
dc.date.available2021-07-28T14:53:12Z
dc.date.issued2017-06-24
dc.descriptionPublication history: Accepted - 31 May 2017; Published online - 24 June 2017.en_US
dc.description.abstractBackground: 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 pathologyen_US
dc.description.sponsorshipWe acknowledge financial support from the Biotechnology and Biological Sciences Research Council through CEDFAS initiative grants BB/E018386/1 and BB/E018335/1 and 2 and Animal Health Research Club grant BB/L004054/1; EJ Glass, JA Woolliams and SC Bishop were also supported by the Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Grants (ISP3 Innate Immunity & Endemic Disease) [BB/J004227/1], (ISP1 Analysis and Prediction in Complex Animal Systems) [BB/J004235/1] and (ISP2 Control of Infectious Diseases) [BB/P013740/1].en_US
dc.identifierhttp://hdl.handle.net/20.500.12518/330
dc.identifier.citationWilkinson, 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.en_US
dc.identifier.issn1471-2164 (electronic)
dc.identifier.urihttps://doi.org/10.1186/s12864-017-3836-x
dc.language.isoenen_US
dc.publisherBMCen_US
dc.rights© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en_US
dc.titleFine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cowsen_US
dc.typeArticleen_US

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