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Common HLA alleles, rather than rare mutants, confer susceptibility to coeliac disease

Brett, PM; Yiannakou, JY; Morris, MA; Vaughan, R; Curtis, D; Ciclitira, PJ; (1999) Common HLA alleles, rather than rare mutants, confer susceptibility to coeliac disease. ANN HUM GENET , 63 217 - 225.

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Abstract

Coeliac Disease (CD) is a gluten sensitive enteropathy characterised by villous atrophy and crypt cell hyperplasia. It has a very strong HLA class II association to the DQ locus. The nature of the involvement of the DQ locus in the susceptibility to CD has been examined by tissue culture experiments, association and peptide binding studies. We examined the role of the DQ molecules in the pathogenesis from the perspective of a genetic family study. Using flanking microsatellite markers to the class II region of the MHC to establish the parental origin of the susceptibility DQ alleles, we hare evidence suggesting that the HLA association is probably due to the necessity to have these DQ alleles in order to express CD and there is no support for the presence of a rare mutation within the DQ alleles nor any rare HLA-linked gene nearby in linkage disequilibrium with the DQ locus. This approach is applicable to other diseases demonstrating strong association with common alleles, and can be used to predict whether screening the region for rare mutations is likely to be worthwhile.

Type: Article
Title: Common HLA alleles, rather than rare mutants, confer susceptibility to coeliac disease
Keywords: CLASS-II ALLELES, MAJOR HISTOCOMPATIBILITY COMPLEX, CELIAC-DISEASE, ASSOCIATIONS, HAPLOTYPE, TAP2, DQ
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute > Biomaterials and Tissue Eng
URI: http://discovery.ucl.ac.uk/id/eprint/31559
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