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Human Molecular Genetics Advance Access published online on February 5, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh079
© 2004 by Oxford University Press
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©2004 Oxford University Press

Article

GENETICS OF INFLAMMATORY BOWEL DISEASE: PROGRESS AND PROSPECTS

Christopher G. Mathew 1* and Cathryn M. Lewis 1

1 Division of Genetics and Development, Guy's, King's and St Thomas's School of Medicine, King's College London, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, UK

* To whom correspondence should be addressed. E-mail: christopher.mathew{at}kcl.ac.uk.


  Abstract

Strong epidemiological evidence for a genetic contribution to pathogenesis in inflammatory bowel disease (IBD) has stimulated efforts to identify susceptibility genes for both of its major clinical forms, Crohn's disease and ulcerative colitis. Genome scans for linkage have indicated multiple regions of interest, but replication of these has been limited. The detection of linkage on chromosome 16 (IBD1) led to the unequivocal identification of the NOD2 gene (now called CARD15) as a susceptibility gene for Crohn's disease. This seminal discovery has provided proof of principle for positional cloning and candidate gene approaches to identify IBD genes. It has also led to useful strategic insights in complex disease genetics, and generated new directions in the investigation of the molecular pathways to pathogenesis. Linkage and association studies have also provided strong support for IBD susceptibility genes on chromosomes 5q31, 6p21 and 19p, while loci of interest at 3p, 3q and 14q require further follow-up. Although important obstacles to further progress will need to be overcome, the successes of the past two years suggest that a detailed description of the genetic basis of inflammatory bowel disease is a realistic goal.


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