Premium
Common HLA alleles, rather than rare mutants, confer susceptibility to coeliac disease
Author(s) -
BRETT P. M.,
YIANNAKOU J. Y.,
MORRIS MA.,
VAUGHAN R.,
CURTIS D.,
CICLITIRA P. J.
Publication year - 1999
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1046/j.1469-1809.1999.6330217.x
Subject(s) - allele , locus (genetics) , genetics , biology , human leukocyte antigen , linkage disequilibrium , coeliac disease , major histocompatibility complex , haplotype , gene , disease , antigen , medicine , pathology
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 have 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.