A genome-wide search identifies potential new susceptibility loci for Crohn's disease

Chronic inflammatory bowel disease (IBD) presents as two major clinical for ms, Crohn's disease (CD) and ulcerative colitis (UC). Genetic epidemiologic al studies and animal models suggest that inherited factors play significan t roles in the susceptibility to both forms of IBD. From four genome-wide s cans, putative susceptibility loci on chromosome 16 (IBD1 for CD), and on c hromosomes 1, 3, 4, 6, 7, 10, and 12 for IBD, have been identified. Several other groups, including ours, have confirmed linkage to the loci on chromo somes 12 and 16. The aim of this study is to identify other potential susce ptibility loci for CD with a genome-wide search approach. In our sample of 222 individuals from 46 families (20 Jewish and 26 non-Jewish), with a tota l of 65 sibpairs diagnosed with CD, we observed a novel locus with suggesti ve linkage [multipoint logarithm of the odds score (Mlod) >2] at chromosome 14q11.2 (Mlod = 2.8, p = 0.0002). In addition, suggestive linkage was obse rved in our Jewish families at chromosome 17q21-q23 (Mlod = 2.1, p = 0.01) and chromosome 5q33-q35 (Mlod = 2.2, p = 0.0003). The syntenic regions of t he latter locus are mapped within two putative loci on mouse chromosomes 11 and 18, which were identified in a mouse IBD model induced by dextran sulf ate sodium (29). Our preliminary results provide potential evidence for sev eral susceptibility loci contributing to the risk of CD. The observation of man-mouse synteny may accelerate the identification of CD susceptibility g ene(s) on human chromosome 5.