A comprehensive mapping of the structure and gene organisation in the sheep MHC class I region

Siva Subramaniam, N., Morgan, E.F., Wetherall, J.D., Stear, M..J. and Groth, D.M. (2015) A comprehensive mapping of the structure and gene organisation in the sheep MHC class I region. BMC Genomics, 16, 810. (doi: 10.1186/s12864-015-1992-4) (PMID:26480943) (PMCID:PMC4613773)

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Background The major histocompatibility complex (MHC) is a chromosomal region that regulates immune responsiveness in vertebrates. This region is one of the most important for disease resistance because it has been associated with resistance or susceptibility to a wide variety of diseases and because the MHC often accounts for more of the variance than other loci. Selective breeding for disease resistance is becoming increasingly common in livestock industries, and it is important to determine how this will influence MHC polymorphism and resistance to diseases that are not targeted for selection. However, in sheep the order and sequence of the protein coding genes is controversial. Yet this information is needed to determine precisely how the MHC influences resistance and susceptibility to disease. Methods CHORI bacterial artificial chromosomes (BACs) known to contain sequences from the sheep MHC class I region were sub-cloned, and the clones partially sequenced. The resulting sequences were analysed and re-assembled to identify gene content and organisation within each BAC. The low resolution MHC class I physical map was then compared to the cattle reference genome, the Chinese Merino sheep MHC map published by Gao, et al. (2010) and the recently available sheep reference genome. Results Immune related class I genes are clustered into 3 blocks; beta, kappa and a novel block not previously identified in other organisms. The revised map is more similar to Bovidae maps than the previous sheep maps and also includes several genes previously not annotated in the Chinese Merino BAC assembly and others not currently annotated in the sheep reference chromosome 20. In particular, the organisation of nonclassical MHC class I genes is similar to that present in the cattle MHC. Sequence analysis and prediction of amino acid sequences of MHC class I classical and nonclassical genes was performed and it was observed that the map contained one classical and eight nonclassical genes together with three possible pseudogenes. Conclusions The comprehensive physical map of the sheep MHC class I region enhances our understanding of the genetic architecture of the class I MHC region in sheep and will facilitate future studies of MHC function.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Stear, Professor Mike
Authors: Siva Subramaniam, N., Morgan, E.F., Wetherall, J.D., Stear, M..J., and Groth, D.M.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:BMC Genomics
Publisher:Biomed Central
ISSN (Online):1471-2164
Copyright Holders:Copyright © 2015 Siva Subramaniam et al.
First Published:First published in BMC Genomics 16:810
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
629831The influence of selective breeding on MHC diversityMichael StearBiotechnology and Biological Sciences Research Council (BBSRC)BB/L004070/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED