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* Department of Experimental Immunology and
Department of Genome Analysis, Helmholtz Centre for Infection Research, Braunschweig, Germany; and
Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
Although the entire mouse genome has been sequenced, there remain challenges concerning the elucidation of particular complex and polymorphic genomic loci. In the murine Igh locus, different haplotypes exist in different inbred mouse strains. For example, the Ighb haplotype sequence of the Mouse Genome Project strain C57BL/6 differs considerably from the Igha haplotype of BALB/c, which has been widely used in the analyses of Ab responses. We have sequenced and annotated the 3' half of the Igha locus of 129S1/SvImJ, covering the CH region and approximately half of the VH region. This sequence comprises 128 VH genes, of which 49 are judged to be functional. The comparison of the Igha sequence with the homologous Ighb region from C57BL/6 revealed two major expansions in the germline repertoire of Igha. In addition, we found smaller haplotype-specific differences like the duplication of five VH genes in the Igha locus. We generated a VH allele table by comparing the individual VH genes of both haplotypes. Surprisingly, the number and position of DH genes in the 129S1 strain differs not only from the sequence of C57BL/6 but also from the map published for BALB/c. Taken together, the contiguous genomic sequence of the 3' part of the Igha locus allows a detailed view of the recent evolution of this highly dynamic locus in the mouse.
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 research was supported by the German Bundesministerium für Bildung und Forschung through Grant PT DLR (FKZ 01KW0003) and the Bioinformatics Competence Centre "Intergenomics" Grant 031U110A/031U210A and National Institutes of Health Grant R01 AI23548.
2 I.R. and C.C. are co-first authors.
3 Current address: Institut National de la Santé et de la Recherche Médicale, Immunology and Genetics of Parasitic Diseases, Marseille, France and Laboratory of Parasitology-Mycology, Faculté de Medecine, Université de la Méditerranée, Marseille, France.
4 H.B., W.M., and R.R. are co-last authors.
5 Address correspondence and reprint requests to Prof. Werner Muller at his current address: University of Manchester, Bill Ford Chair of Cellular Immunology, Michael Smith Building, Oxford Road, Manchester, U.K.
6 Abbreviations used in this paper: RSS, recombination signal sequence; BAC, bacterial artificial chromosome; STS, sequence-tagged site; PIP, percent identity plot; YAC, yeast artificial chromosome.
7 The online version of this article contains supplemental material.
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