Ulcerative colitis and Crohns disease: molecular genetics and clinical implications.

Derek Jewell Professor of Gastroenterology, Gastroenterology Unit, Radcliffe Infirmary, Oxford, OX2 6HE, UK. Tel: +44 (0) 1865 224829; Fax: +44 (0) 1865 790792; E-mail: [email protected] The genetics of inflammatory bowel disease (IBD) is an area of enormous topical interest. Crohn’s disease is one of the first polygenic diseases in which a susceptibility gene (NOD2 ) has been positionally cloned, providing proof of principle for methodologies that to date had been mired in uncertainty. IBD has been highly unusual among polygenic diseases in providing replicated candidate susceptibility regions using genome-scanning methodologies and linkage analysis. Such studies have identified loci with replicated evidence for linkage on chromosomes 1, 3, 6, 12, 14 and 16 – the latter recently yielding NOD2. The next stage is fine mapping each of the remaining candidate loci and identifying the precise genes involved. Although progress is slow, the identification of NOD2 together with technological advances and the availability of increasingly large panels of patients and multiply affected families provide the basis for great optimism. The ultimate goal is a better understanding of disease pathogenesis – both genetic and environmental – with a rational redefinition of Crohn’s disease and ulcerative colitis, and a rational, specific therapeutic approach to each genotypically defined subclass of IBD.