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* Institute for Animal Health, Compton, Berkshire, United Kingdom;
Basel Institute for Immunology, Basel, Switzerland; and
Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom
Compared with the MHC of typical mammals, the chicken MHC (BF/BL region) of the B12 haplotype is smaller, simpler, and rearranged, with two classical class I genes of which only one is highly expressed. In this study, we describe the development of long-distance PCR to amplify some or all of each class I gene separately, allowing us to make the following points. First, six other haplotypes have the same genomic organization as B12, with a poorly expressed (minor) BF1 gene between DMB2 and TAP2 and a well-expressed (major) BF2 gene between TAP2 and C4. Second, the expression of the BF1 gene is crippled in three different ways in these haplotypes: enhancer A deletion (B12, B19), enhancer A divergence and transcription start site deletion (B2, B4, B21), and insertion/rearrangement leading to pseudogenes (B14, B15). Third, the three kinds of alterations in the BF1 gene correspond to dendrograms of the BF1 and poorly expressed class II B (BLB1) genes reflecting mostly neutral changes, while the dendrograms of the BF2 and well-expressed class II (BLB2) genes each have completely different topologies reflecting selection. The common pattern for the poorly expressed genes reflects the fact the BF/BL region undergoes little recombination and allows us to propose a pattern of descent for these chicken MHC haplotypes from a common ancestor. Taken together, these data explain how stable MHC haplotypes predominantly express a single class I molecule, which in turn leads to striking associations of the chicken MHC with resistance to infectious pathogens and response to vaccines.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Biotechnology and Biological Sciences Research Council (U.K.), by F. Hofmann-La Roche SA (Switzerland), and by The Wellcome Trust for The Sanger Institute.
2 I.S. and T.J.P. contributed equally to the work in this paper.
3 Current address: National University of Ireland, National Diagnostics Centre, Galway, University Road, Galway, Ireland.
4 Current address: Trudeau Institute, Saranac Lake, NY 12983.
5 Current address: Veterinary Laboratories Agency at Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, U.K.
6 Current address: General Bioinformatics, The Enterprise Hub, University of Reading, Berkshire RG6 6AU, U.K.
7 Current address: Cancer Sciences Division, University of Southampton School of Medicine, Southampton, SO16 6YD, U.K.
8 Current address: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609-1500.
9 Address correspondence and reprint requests to Dr. Jim Kaufman, Institute for Animal Health, Compton, Berkshire, RG20 7NN, U.K. E-mail address: jim. kaufman{at}bbsrc.ac.uk
10 Abbreviations used in this paper: SNP, single nucleotide polymorphism; UTR, untranslated region.
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