Additional evidence of linkage between Crohn's disease and a putative locus on chromosome 12

The inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis (UC) are chronic intestinal disorder of unknown etiology. Genetic factors play an important role in the pathogenesis of these diseases, but w ith a complex pattern of inheritance. A number of genome-wide scans have id entified several putative susceptibility loci for both CD and UC, including a locus on chromosome 12 reported in a set of British families. We aim to evaluate the linkage between CD or UC and this chromosome 12 locus in an in dependent set of U.S. Caucasian families (36% being of Ashkenazi Jewish ori gin). Methods: Microsatellite markers along chromosome 12 spaced at approxi mately 10 cm intervals were used to test the putative loci in CD only famil ies (65 sib pairs from 46 families). Regions with positive linkage for CD w ere then tested in a panel of UC and mixed families (44 sib pairs from 29 f amilies). Two point linkage analysis was performed with SIBPAL. Multipoint linkage analysis was carried out with MAPMAKER/SIBS. Results: We observed e vidence of linkage between the region on chromosome 12 and Crohn's disease, because there was a significant excess of allele sharing in CD sib pairs ( pi = 0.62, p = 0.0004 from two-point linkage; and logarithm of the odds sco re (LOD) = 2.0 from multipoint linkage). However, we did not observe the sa me linkage in UC and mixed families (p = 0.48; not significant [ns]). Concl usion: Our data provided further evidence that the region on chromosome 12 is likely to contain a gene predisposing to CD.