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* Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Kanagawa, Japan;
Division of Molecular Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010;
Laboratory of Animal Physiology, Faculty of Agriculture, Tokyo University of Agriculture, Kanagawa, Japan;
Centre for Forensic Science, The University of Western Australia, Nedlands, Western Australia, Australia; and
¶ Department of Bioresource Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima, Japan
The Mhc is a highly conserved gene region especially interesting to geneticists because of the rapid evolution of gene families found within it. High levels of Mhc genetic diversity often exist within populations. The chicken Mhc is the focus of considerable interest because of the strong, reproducible infectious disease associations found with particular Mhc-B haplotypes. Sequence data for Mhc-B haplotypes have been lacking thereby hampering efforts to systematically resolve which genes within the Mhc-B region contribute to well-defined Mhc-B-associated disease responses. To better understand the genetic factors that generate and maintain genomic diversity in the Mhc-B region, we determined the complete genomic sequence for 14 Mhc-B haplotypes across a region of 59 kb that encompasses 14 gene loci ranging from BG1 to BF2. We compared the sequences using alignment, phylogenetic, and genome profiling methods. We identified gene structural changes, synonymous and non-synonymous polymorphisms, insertions and deletions, and allelic gene rearrangements or exchanges that contribute to haplotype diversity. Mhc-B haplotype diversity appears to be generated by a number of mutational events. We found evidence that some Mhc-B haplotypes are derived by whole- and partial-allelic gene conversion and homologous reciprocal recombination, in addition to nucleotide mutations. These data provide a framework for further analyses of disease associations found among these 14 haplotypes and additional haplotypes segregating and evolving in wild and domesticated populations of chickens.
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 The nucleotide sequences reported in this work have been submitted to GenBank under accession nos. AB426141 to AB426154.
2 This work was supported by KAKENHI (Grant-in-Aid for Scientific Research) on Priority Areas "Comparative Genomics" from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Advanced Research Project Type A, Tokyo University of Agriculture, No. 02, 2006; NIH NCI R21 CA105426; and USDA CREES NRICGP 2006-35205-16678.
3 Address correspondence and reprint requests to Dr. Takashi Shiina, Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1143, Japan. E-mail address: tshiina{at}is.icc.u-tokai.ac.jp
4 Abbreviations used in this paper: LR-PCR, long-range PCR; indel, insertion and deletion; dN, nonsynonymous substitution; dS, synonymous substitution; SNP, sequence diversity.
5 The online version of this article contains supplemental material.
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