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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents

ID: 268558.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Dissection of the inflammatory bowel disease transcriptome using genome-wide cDNA microarrays
Authors:Costello, Christine M.; Mah, Nancy; Häsler, Robert; Rosenstiel, Philip; Waetzig, Georg H.; Hahn, Andreas; Lu, Tim; Gurbuz, Yesim; Nikolaus, Susanna; Albrecht, Mario; Hampe, Jochen; Lucius, Ralph; Klöppel, Günther; Eickhoff, Holger; Lehrach, Hans; Lengauer, Thomas; Schreiber, Stefan
Date of Publication (YYYY-MM-DD):2005-08-23
Title of Journal:PLoS Medicine
Journal Abbrev.:PLoS Med
Issue / Number:8:e199
Start Page:1
End Page:17
Copyright:© 2005 Costello et al
Review Status:not specified
Audience:Experts Only
Abstract / Description:Background

The differential pathophysiologic mechanisms that trigger and maintain the two forms of inflammatory bowel disease (IBD), Crohn disease (CD), and ulcerative colitis (UC) are only partially understood. cDNA microarrays can be used to decipher gene regulation events at a genome-wide level and to identify novel unknown genes that might be involved in perpetuating inflammatory disease progression.
Methods and Findings

High-density cDNA microarrays representing 33,792 UniGene clusters were prepared. Biopsies were taken from the sigmoid colon of normal controls (n = 11), CD patients (n = 10) and UC patients (n = 10). 33P-radiolabeled cDNA from purified poly(A)+ RNA extracted from biopsies (unpooled) was hybridized to the arrays. We identified 500 and 272 transcripts differentially regulated in CD and UC, respectively. Interesting hits were independently verified by real-time PCR in a second sample of 100 individuals, and immunohistochemistry was used for exemplary localization. The main findings point to novel molecules important in abnormal immune regulation and the highly disturbed cell biology of colonic epithelial cells in IBD pathogenesis, e.g., CYLD (cylindromatosis, turban tumor syndrome) and CDH11 (cadherin 11, type 2). By the nature of the array setup, many of the genes identified were to our knowledge previously uncharacterized, and prediction of the putative function of a subsection of these genes indicate that some could be involved in early events in disease pathophysiology.

A comprehensive set of candidate genes not previously associated with IBD was revealed, which underlines the polygenic and complex nature of the disease. It points out substantial differences in pathophysiology between CD and UC. The multiple unknown genes identified may stimulate new research in the fields of barrier mechanisms and cell signalling in the context of IBD, and ultimately new therapeutic approaches.
Comment of the Author/Creator:The authors have declared that no competing interests exist.
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Institute for Clinical Molecular Biology, University Hospital Schleswig Holstein, Christian-Albrechts University of Kiel, Kiel, Germany;
CONARIS Research Institute, Kiel, Germany, 3 Department of Computational Biology and Applied Algorithmics, Max-Planck-Institute for Informatics, Saarbrücken, Germany; Institute of Pathology, University Hospital Schleswig Holstein, Kiel, Germany;
Department of General Internal Medicine, University Hospital Schleswig Holstein, Kiel, Germany;
Institute of Anatomy, University Hospital Schleswig Holstein, Kiel, Germany
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