Abstract
Crohn's disease (CD) is a complex genetic disorder for which a susceptibility gene, IBD1, has been mapped within the pericentromeric region of chromosome 16. In order to refine the location of IBD1, 77 multiplex CD families were genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37×10−4) in a region centred by markers D16S3136, D16S3117 and D16S770. 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 analyses demonstrated suggestive association between the 207 bp allele of D16S3136 (P<0.05) and a new biallellic marker hb27g11f-end (P=0.01). These markers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step before an exhaustive linkage disequilibrium mapping of putatively transcribed regions to identify IBD1.
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Acknowledgements
We gratefully acknowledge the participation of the patients and their families. Families for the study were kindly recruited by Drs Joaquin Balanzo, Vibeke Binder, Bruno Bonaz, Yoram Bouhnik, Guillaume Cadiot, Antoine Cortot, Bart Crusius, Salvatore Cucchiara, Jean-Jacques Delchier, Bernard Duclos, Jean-Louis Dupas, Jean-Paul Galmiche, Jean-Pierre Gendre, Denis Golfain, Christer Grännö, Denis Heresbach, André Lachaux, Hervé Lautraite, Catherine Lenaerts, Eric Lerebours, Victor Levy, Robert Löfberg, Helmut Malchow, Philippe Marteau, Alain Morali, Francesco Pallone, Salvatore Pena, André Rotenberg, Isabelle Rousseau, Jacques Schmitz, Fergus Shanahan, Iradj Sobhani, Hans Svensson, André Van Gossum, Myriam Van Winckel and Michel Veyrac. For their excellent technical assistance we are grateful to: Jean Christophe Beaudoin, Christophe Billon, The Hung Bui, Lucien Cazes, Fabrice Chareyre, Catherine Giudicelli, Laetitia Gressin, Sonia Kemergi, Marie Legrand, Anna Martins, Catherine Massart, Mourad Sahbatou, Emmanuel Tubacher, Héra Der Sarkissian. This project received financial support from: the European Community (Contract Biomed 2 no BMH4-97-2098), the Ministère Français de l'Education Nationale et de la Recherche, the INSERM, the Direction Générale de la santé (convention no 4T004C), the Association François Aupetit and the Institut de Recherche des Maladies de l'Appareil Digestif and the Swedish Society of Medicine.
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Zouali, H., Chamaillard, M., Lesage, S. et al. Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease. Eur J Hum Genet 9, 731–742 (2001). https://doi.org/10.1038/sj.ejhg.5200710
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DOI: https://doi.org/10.1038/sj.ejhg.5200710
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