Coeliac disease: follow-up linkage study provides further support for existence of a susceptibility locus on chromosome 11p11
Article first published online: 7 FEB 2003
© 2001 University College London
Annals of Human Genetics
Volume 65, Issue 4, pages 377–386, July 2001
How to Cite
KING, A. L., FRASER, J. S., MOODIE, S. J., CURTIS, D., DEARLOVE, A. M., ELLIS, H. J., ROSEN-BRONSON, S. and CICLITIRA, P. J. (2001), Coeliac disease: follow-up linkage study provides further support for existence of a susceptibility locus on chromosome 11p11. Annals of Human Genetics, 65: 377–386. doi: 10.1046/j.1469-1809.2001.6540377.x
- Issue published online: 7 FEB 2003
- Article first published online: 7 FEB 2003
- Cited By
Susceptibility to coeliac disease has a strong genetic component. The HLA associations have been well described but it is clear that other genes outside this region must also be involved in disease development. Two previous genome-wide linkage studies using the affected sib pair method produced conflicting results. Our own family based linkage study of 16 highly informative pedigrees identified 17 possibly linked regions, each of which produced a result significant at p < 0.05 or less.
We have now investigated these 17 regions in a larger set of pedigrees using more finely spaced markers. Fifty multiply affected families were studied, comprising the 16 pedigrees from the original genome screen plus 34 new highly informative pedigrees. A total of 128 microsatellite markers were genotyped with an average spacing between markers of 5 cM. Two-point and three-point linkage analysis using classical and model free methods identified five potential susceptibility loci with heterogeneity lod scores > 2.0, at 6p12, 11p11, 17q12, 18q23 and 22q13.3. The most significant was a heterogeneity lod of 2.6 at D11S914 on chromosome 11p11. This marker maps to a position implicated in one of the two previous genome scans and taken together these results provide strong support for the existence of a susceptibility locus in this region.