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

1999; Elsevier BV; Volume: 1; Issue: 5 Linguagem: Inglês

10.1097/00125817-199907000-00005

1530-0366

Huiying Yang, Ohmen Jd, Yan Ma, Bentley Lg, Targan, Nathan Fischel‐Ghodsian, Rotter Ji,

RNA Research and Splicing

Purpose: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 with a complex pattern of inheritance.A number of genome-wide scans have identified several putative susceptibility loci for both CD and UC, including a locus on chromosome 1 2 reported in a set of British faniil~es.We aim to evaluate the linkage between CD or UC and this chromosome 1 2 locus in an independent set of U.S. Caucasian families (36% being of Ashkenazi Jewish origln).Methods: Microsatellite markers along chromosome 1 2 spaced at approximately 1 0 cm intervals were used to test the putative loci in CD only families (65 sib pairs from 46 families).Regions with pos~tive linkage for CD were then tested in a panel of UC and mixed families (44 sib pairs from 29 families).Two point linkage analysis was performed with SIBPAL.Multipoint linkage analysis was carried out with MAPMAKER/SIBS.Results: We observed evidence of linkage between the region on chromosome 1 2 and Crohn's disease, because there was a significant excess of allele sharing in CD sib pairs (TT = 0.62, p = 0.0004 from two-point linkage; and logarithm of the odds score (LOD) = 2.0 from multipoint linkage).However, we did not observe the same linkage in UC and mixed families ( p = 0.48; not significant [ns]).Conclusion: Our data provided further evidence that the region on chromosome 1 2 is likely to contain a gene predisposing to CD.