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G.P.13.17 Recombinant mapping of MHC susceptibility region in sporadic inclusion body myositis (sIBM)

Scott, A., Laing, N., Mastaglia, F., Needham, M., Walter, M., Dalakas, M. and Allcock, R. (2007) G.P.13.17 Recombinant mapping of MHC susceptibility region in sporadic inclusion body myositis (sIBM). Neuromuscular Disorders, 17 (9-10). pp. 853-854.

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Susceptibility to sIBM is associated with alleles of the major histocompatibility complex (MHC) on chromosome 6. Several studies have shown an association between sIBM and the highly conserved 8.1 ancestral haplotype (AH). However the strong linkage disequilibrium that exists within the MHC has so far prevented definitive identification of the genes responsible within a 270 kb region between AGER and HLA-DRA. This region contains nine candidate genes at least one of which must play a role in sIBM susceptibility. This study sought to refine the susceptibility region by mapping 8.1AH-specific alleles in patients possessing a complete or partial 8.1AH with the intention of isolating single or multiple alleles directly associated with sIBM. By locating a susceptibility allele(s), we hope that this will assist in elucidating the pathogenesis of sIBM and contribute to efforts in developing an effective treatment for the disease. Individuals carrying markers of the 8.1AH between HLA-DR and AGER selected from a cohort of 120 Caucasian sIBM patients were typed for alleles of multiple polymorphisms and microsatellites to define the haplotype recombination points and thus the disease susceptibility region, as defined by what part of the 8.1AH they possess. Each individual’s susceptibility region was then compared to determine overlapping tracts of DNA. Recombinant mapping showed evidence of two non-overlapping regions of the 8.1AH, from AGER to LOC401252 and from C6orf10 to HLA-DRA, shared by multiple patients. The data were also used to more accurately differentiate patients with the 8.1AH from those without. These findings indicate that there is unlikely to be a single susceptibility allele for sIBM in individuals carrying the 8.1AH, but that multiple alleles between AGER and HLA-DR may independently contribute to disease susceptibility.

Item Type: Journal Article
Publisher: Elsevier BV
Copyright: © 2007 Published by Elsevier B.V.
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