An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistance

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dc.contributor.authorTsairidou, S.
dc.contributor.authorAllen, Adrian
dc.contributor.authorPong-Wong, R.
dc.contributor.authorMcBride, S.H.
dc.contributor.authorWright, D.M.
dc.contributor.authorMatika, O.
dc.contributor.authorPooley, C.M.
dc.contributor.authorMcDowell, Stanley W.J.
dc.contributor.authorGlass, E.J.
dc.contributor.authorSkuce, Robin A.
dc.contributor.authorBishop, S.C.
dc.contributor.authorWoolliams, J.A.
dc.date.accessioned2021-06-22T13:53:15Z
dc.date.available2021-06-22T13:53:15Z
dc.date.issued2018-01-24
dc.descriptionPublication history: Accepted - 23 November 2017; Published online - 24 January 2018en_US
dc.description.abstractGenetic selection of cattle more resistant to bovine tuberculosis (bTB) may offer a complementary control strategy. Hypothesising underlying non-additive genetic variation, we present an approach using genome-wide high density markers to identify genomic loci with dominance effects on bTB resistance and to test previously published regions with heterozygote advantage in bTB. Our data comprised 1151 Holstein–Friesian cows from Northern Ireland, confirmed bTB cases and controls, genotyped with the 700K Illumina BeadChip. Genome-wide markers were tested for associations between heterozygosity and bTB status using marker-based relationships. Results were tested for robustness against genetic structure, and the genotypic frequencies of a significant locus were tested for departures from Hardy-Weinberg equilibrium. Genomic regions identified in our study and in previous publications were tested for dominance effects. Genotypic effects were estimated through ASReml mixed models. A SNP (rs43032684) on chromosome 6 was significant at the chromosome-wide level, explaining 1.7% of the phenotypic variance. In the controls, there were fewer heterozygotes for rs43032684 (P < 0.01) with the genotypic values suggesting that heterozygosity confers a heterozygote disadvantage. The region surrounding rs43032684 had a significant dominance effect (P < 0.01). SNP rs43032684 resides within a pseudogene with a parental gene involved in macrophage response to infection and within a copy-number-variation region previously associated with nematode resistance. No dominance effect was found for the region on chromosome 11, as indicated by a previous candidate region bTB study. These findings require further validation with large-scale data.en_US
dc.description.sponsorshipWe are grateful for the financial support from the University of Edinburgh and the Roslin Institute, through the Principal's Career Development Scholarship (ST), and the Biotechnology and Biological Sciences Research Council institute strategic project ISP3: BB/P013759/1 (JAW). We would also like to thank BBSRC for their support through CEDFAS initiative grants BB/E018386/1 (RS); EJG; SCB; JAW also received support through CEDFAS grants: BB/E018335/1 and 2; Animal Health Research Club grant BB/L004054/1; 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/20.500.12518/288
dc.identifier.citationTsairidou, S., Allen, A. R., Pong-Wong, R., McBride, S. H., Wright, D. M., Matika, O., Pooley, C. M., McDowell, S. W. J., Glass, E. J., Skuce, R. A., Bishop, S. C. and Woolliams, J. A. (2018) ‘An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistance’, Animal Genetics, 49(2), pp. 103–109. doi: 10.1111/age.12637.en_US
dc.identifier.issn0268-9146
dc.identifier.urihttps://doi.org/10.1111/age.12637
dc.language.isoenen_US
dc.publisherWileyen_US
dc.rights© 2018 The Authors. Animal Genetics published by John Wiley & Sons Ltd 103 on behalf of Stichting International Foundation for Animal Genetics, 49, 103–109 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly citeden_US
dc.subjectdisease resistanceen_US
dc.subjectdominanceen_US
dc.subjectgenome-wide association studyen_US
dc.subjectgenomic selectionen_US
dc.titleAn analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistanceen_US
dc.typeArticleen_US
dcterms.dateAccepted2017-11-21

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