Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis

Inflammatory bowel disease (IBD) is a chronic relapsing disorder affecting the gastro-intestinal tract and is subdivided into two main subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Although the aetiology of IBD is unknown, a strong genetic susceptibility is suggested and different candidate regions have been identified for both CD and UC. The IBD1 region on chromosome 16 has been confirmed to be important for susceptibility to CD, whereas conflicting evidence has been obtained for UC. We performed a combined linkage and segregation analysis in the identified IBD1 region on a sample of 82 extended families with IBD using a parametric method implemented in the computer program COMDS. This approach allows simultaneous evaluation of linkage while estimating the mode of inheritance and to include severity of the trait to characterise the CD and UC phenotypes. Our results are consistent with the presence of a major gene in the IBD1 region close to D16S408 involved in both UC and CD. Furthermore, our data support evidence that a single mutation in the gene leads more frequently to UC, whereas inheritance of two mutant alleles results in the more severe CD. In our study the IBD1 locus was found to have a major role in IBD predisposition in the Italian population.