Human Molecular Genetics, 2000, Vol. 9, No. 9 1425-1432
© 2000 Oxford University Press
Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease
The Martin Boyer Genetics Research Laboratories, Gastroenterology and 1Hematology/Oncology sections, Department of Medicine and 2Department of Statistics, The University of Chicago Hospitals, 5841 South Maryland Avenue, MC6084, Chicago, IL 60637, USA, 3The Harvey M. and Lynn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, The Johns Hopkins University School of Medicine, 918 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA, 4DMC/Sinai Hospitals, Detroit, MI, USA
The idiopathic inflammatory bowel diseases (IBDs), consisting of Crohn’s disease and ulcerative colitis, are complex genetic disorders involving chronic inflammation of the intestines. Multiple genetic loci have been implicated through genome-wide searches, but refinement of localization sufficient to undertake positional cloning efforts has been problematic. This difficulty can be obviated through identification of ancestrally shared regions in genetic isolates, such as the Chaldean population, a Roman Catholic group from Iraq. We analyzed four multiply affected American Chaldean families with inflammatory bowel disease not known to be related. We observed evidence for linkage and linkage disequilibrium in precisely the same region of chromosome band 1p36 reported previously in an outbred population. Maximal evidence for linkage was observed near D1S1597 by multipoint analysis (MLOD = 3.01, P = 6.1 x 10–5). A shared haplotype (D1S507 to D1S1628) was observed over 27 cM between two families. There was homozygous sharing of a 5 cM portion of that haplotype in one family and over a <1 cM region in the second family. Homozygous sharing of this haplotype near D1S2697 and D1S3669 was observed in one individual in a third multiply affected family, with heterozygous sharing in a fourth family. Linkage in outbred families as well as in this genetic isolate indicates that a pathophysiologically crucial IBD susceptibility gene is located in 1p36. These findings provide a unique opportunity to refine the localization and identify a major susceptibility gene for a complex genetic disorder.
+ To whom correspondence should be addressed. Tel: +1 773 702 5375; Fax: +1 773 702 2281; Email: jcho@medicine.bsd.uchicago.edu
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