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Generation and maintenance of diversity in the cattle MHC class I region

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Abstract

Major histocompatibility complex (MHC) class I genes play a crucial role in the immune defence against intracellular pathogens. An important evolutionary strategy is to generate and maintain a high level of diversity in these genes. Humans express three highly polymorphic classical MHC class I genes (HLA-A, HLA-B and HLA-C). In contrast, some species, for example rat and rhesus macaque, maintain diversity by generation of haplotypes that vary considerably with regard to the number and combination of transcribed genes. Cattle appear to use both strategies. We show that various combinations of six apparently classical genes, three of which are highly polymorphic, are transcribed on different haplotypes. Although additional sequences were identified in both cDNA and gDNA, it was not possible to assign them to any of these defined genes. Most were highly divergent or were non-classical class I genes. Thus, we found little evidence for frequent duplication and deletion of classical class I genes as reported in some other species. However, the maintenance of class I diversity in cattle may involve limited gene shuffling and deletion, possibly as a result of unequal crossing-over within the class I region.

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Acknowledgements

This work was supported by the Biotechnology and Biological Sciences Research Council, UK. We would like to thank the staff of the IAH farm, Helen Prentice for help with sampling and Alison Burrells for help with sequence analysis. The experiments carried out in this study comply with UK law.

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Correspondence to Shirley A. Ellis.

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The first two authors made an equal contribution to this work.

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Birch, J., Murphy, L., MacHugh, N.D. et al. Generation and maintenance of diversity in the cattle MHC class I region. Immunogenetics 58, 670–679 (2006). https://doi.org/10.1007/s00251-006-0137-y

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