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          Institute: MPI für molekulare Genetik     Collection: Research Group Development and Disease     Display Documents

ID: 24745.0, MPI für molekulare Genetik / Research Group Development and Disease
Evidence for a NOD2-independent susceptibility locus for inflammatory bowel disease on chromosome 16p
Authors:Hampe, Jochen; Frenzel, Henning; Mirza, Muddassar M.; Croucher, Peter J. P.; Cuthbert, Andrew; Mascheretti, Silvia; Huse, Klaus; Platzer, Matthias; Bridger, Stephen; Meyer, Birgit; Nürnberg, Peter; Stokkers, Pieter; Krawczak, Michael; Mathew, Christopher G.; Curran, Mark; Schreiber, Stefan
Date of Publication (YYYY-MM-DD):2001-12-18
Title of Journal:Proceedings of the National Academy of Sciences
Issue / Number:1
Start Page:321
End Page:326
Review Status:not specified
Audience:Experts Only
Abstract / Description:Heritable predisposition to inflammatory bowel disease (IBD) has been demonstrated by epidemiological and genetic analysis. Linkage of IBD to broad regions of chromosome 16 has been established by analysis of multiple populations. NOD2, located on proximal 16q, was recently identified as an IBD gene. As the linkage regions on chromosome 16 are large, we have investigated the possibility that NOD2 is not the only IBD gene located on this chromosome. A high-density experiment using 39 microsatellite markers was performed to identify additional regions of association, and to indicate areas of interest for further investigation. A triple-peaked configuration of the linkage curve with peak logarithm of odds (lod) scores of 2.7, 3.2, and 3.1 was observed on proximal 16p, proximal 16q, and central 16q, respectively. The cohort was stratified by coding individuals carrying the NOD2 single nucleotide polymorphism (SNP)8 and SNP13 "unknown." Significance at the central peak, corresponding to the genomic location of NOD2, then decreased from 3.2 to 1.2. The maximal lod scores on the proximal p-arm (lod = 2.1) and central q-arm (lod = 2.6) changed only moderately. An exploratory association analysis (TRANSMIT) yielded a strong lead at D16S3068 (P = 0.00028). The region around this marker was further investigated by using anonymous SNPs. An associated haplotype containing three SNPs was identified (peak significance P = 0.00027, IBD phenotype). On stratification based on NOD2 genotype, this significance increased to P = 0.0001. These results confirm the importance of NOD2 and provide evidence for a second IBD gene located on chromosome 16p.
External Publication Status:published
Document Type:Article
Communicated by:Stefan Mundlos
Affiliations:MPI für molekulare Genetik
External Affiliations:Department of General Internal Medicine, Christian Albrechts University, 24118 Kiel, Germany
Divisions of Medical and Molecular Genetics and of Medicine, Guy's, King's, and St. Thomas' School of Medicine, London WC2R 2LS, United Kingdom
Institute for Molecular Biotechnology, 07745 Jena, Germany Gene Mapping Center, Max Delbrück Center for Molecular Medicine, D-13092 Berlin, Germany
Department of Gastroenterology, Academic Medical Centre, Amsterdam 105AZ, The Netherlands
University of Wales College of Medicine, Cardiff CF 144XN, United Kingdom
Axys Pharmaceuticals, San Diego, CA 92037
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