Human Molecular Genetics, Vol 6, 1335-1339, Copyright © 1997 by Oxford University Press
RS Houlston, IP Tomlinson, D Ford, S Seal, AM Marossy, A Ferguson, GK Holmes, KB Hosie, PD Howdle, DP Jewell, A Godkin, GD Kerr, P Kumar, RF Logan, AH Love, S Johnston, MN Marsh, S Mitton, D O'Donoghue, A Roberts, JA Walker-Smith and MF Stratton
A strong HLA association is seen in coeliac disease [specifically to the
DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account
for the increased risk seen in relatives of affected cases. One or more
genes at HLA-unlinked loci also predispose to coeliac disease and are
probably stronger determinants of disease susceptibility than HLA. A recent
study has proposed a number of candidate regions on chromosomes 6p23
(distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3,
19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked
susceptibility gene. We have examined these regions in 28 coeliac disease
families by linkage analysis. There was excess sharing of chromosome 6p
markers, but no support for a predisposition locus telomeric to HLA. No
significant evidence in favour of linkage to coeliac disease was obtained
for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or
22cen. There was, however, excess sharing close to D15S642. The maximum
non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for
linkage of coeliac disease to chromosome 15q26 is not strong, the well
established association between coeliac disease and insulin dependent
diabetes mellitus, together with the mapping of an IDDM susceptibility
locus (IDDM3) to chromosome 15q26, provide indirect support for this as a
candidate locus conferring susceptibility to coeliac disease in some
families.
ARTICLES
Linkage analysis of candidate regions for coeliac disease genes
Institute of Cancer Research, Sutton, Surrey, UK. r.houlston@icr.ac.uk
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