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A genome-wide family-based linkage study of coeliac disease

Published online by Cambridge University Press:  20 February 2001

A. L. KING ,
J. Y. YIANNAKOU ,
P. M. BRETT ,
D. CURTIS ,
M.-A. MORRIS ,
A. M. DEARLOVE ,
M. RHODES ,
S. ROSEN-BRONSON ,
C. MATHEW  and
H. J. ELLIS
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A. L. KING
Affiliation:
Department of Gastroenterology (GKT), The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, UK
J. Y. YIANNAKOU
Affiliation:
Department of Gastroenterology (GKT), The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, UK
P. M. BRETT
Affiliation:
Periodontology, Eastman Dental Institute, UCL, 256 Gray's Inn Road, London. WC1X 8LD, UK
D. CURTIS
Affiliation:
Academic Department of Psychological Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, 3rd Floor Alexandra Wing, Turner Street, London E1, UK
M.-A. MORRIS
Affiliation:
Department of Gastroenterology (GKT), The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, UK
A. M. DEARLOVE
Affiliation:
UK HGMP Resource Centre, Hinxton, Cambridge CB10 1SB, UK
M. RHODES
Affiliation:
UK HGMP Resource Centre, Hinxton, Cambridge CB10 1SB, UK
S. ROSEN-BRONSON
Affiliation:
Georgetown University Medical Centre, Washington, DC, 20007, USA
C. MATHEW
Affiliation:
Paediatric Research Unit (GKT), Guy's Hospital, London, SE1 9RT, UK
H. J. ELLIS
Affiliation:
Department of Gastroenterology (GKT), The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, UK
P. J. CICLITIRA
Affiliation:
Department of Gastroenterology (GKT), The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, UK
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Abstract

The susceptibility to develop coeliac disease (CD) has a strong genetic component, which is not entirely explained by HLA associations. Two previous genome wide linkage studies have been performed to identify additional loci outside this region. These studies both used a sib-pair design and produced conflicting results.

Our aim is to identify non-MHC genetic loci contributing to coeliac disease using a family based linkage study. We performed a genome wide search in 16 highly informative multiply affected pedigrees using 400 microsatellite markers with an average spacing of 10 cM. Linkage analysis was performed using lod score and model free methods.

We identified two new potential susceptibility loci with lod scores of 1.9, at 10q23.1, and 16q23.3. Significant, but lower lod scores were found for 6q14 (1.2), 11p11 (1.5), and 19q13.4 (0.9), areas implicated in a previous genome wide study. Lod scores of 0.9 were obtained for both D7S507, which lies 1 cM from the γT-cell receptor gene, and for D2S364, which lies 12 cM from the CTLA4 gene.

Type
Research Article
Information
Annals of Human Genetics , Volume 64 , Issue 6 , November 2000 , pp. 479 - 490
Copyright
University College London 2000

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