Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease

Crohn's disease (CD) is a complex genetic disorder for which a susceptibili ty gene, IBD1, has been mapped within the pericentromeric region of chromos ome 16. In order to refine the location of IBD1, 77 multiplex CD families w ere genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37 x 10(-4)) in a region centred by markers D16S3136, D16S3117 and D16 S770. Simulation studies showed that the probability for IBD1 to be located in a 5 cM region around these markers was 70%. A 2.5 Mb YAC and BAC contig map spanning this genetic region on chromosome band 16q12 was built. TDT a nalyses demonstrated suggestive association between the 207 bp allele of D1 6S3136 (P <0.05) and a new biallellic marker hb27g11f-end (P=0.01). These m arkers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step befo re an exhaustive linkage disequilibrium mapping of putatively transcribed r egions to identify IBD1.