Project Acronym:
IBD-Character

Project Reference:
305676

Duration: 52 months

Contract Type:
Small or medium-scale
focused research project

Project Funding:
6 million euros

Research area:
HEALTH.2012.2.4.5-2 Biomarkers and diagnostics for chronic inflammatory diseases of the joint and/or digestive system

This project has received funding from the European Union's Seventh Framework Program for research, technological development and demonstration under grant agreement #305676

Nucleic Acid analysis

Large scale analysis of methylation patterns and transcription profiles will be conducted to complement traditional genotyping, given the low contribution of found genetic alternations to explain for heritability of IBD

Recent advances made by large international consortia, with active contribution of members in this project, have identified a number of susceptibility loci in both ulcerative colitis (UC) and Crohn’s disease (CD) ,  Follow up studies of > 50000 cases and controls, have lead to that now 163 genes/loci and associated SNPs have been confirmed and recently identified as true IBD (CD or UC) genetic susceptibility factors . The project will score information of already existing susceptibility genotypes as a “baseline” for the further analysis and complement the analysis with methylation and transcription profiling within this unique cohort of patients.

The contribution of epigenetic alterations to disease pathogenesis is now emerging as a research priority given the low contribution of found genetic alternations to explain for heritability. To advance the understanding of epigenetic changes in IBD we will perform large scale methylation profiling. The means to analyze and interpret data from large scale methylation studies is still in its early phases but the size of the cohort have been chosen accordingly based on recommendations in recent publications to allow relevant data to be extracted.  . The current study will generate the largest methylation profiling in early IBD patients so far.  Partners within the project have recently found epigenetic factors relevant for development of CD   also in blood. This is a very interesting finding as it opens up for blood based screening of biomarkers as well as explore if epigenetic regulation may represent a target for therapeutic intervention, and it will be further pursued within the project. One of the project aims is to understand the mechanism for initiation of the disease and therefore methylation profiling will also be performed on mucosal biopsies of the actual disease relevant issue. 

To complement the protein assays, as described in the section about proteins, and to facilitate interpretation of the methylation data we will also perform RNA expression analysis on the entire cohort. The RNA expression will be analyzed using high content RNA expression arrays to yield a global view of gene regulation changes in the early stages of IBD.

In addition to array based molecular phenotyping we will perform in depth analysis of a subset of the cohort. Based on the initial diagnose of the IBD patients they will be divided in patients with severe initial disease and more mild symptoms and on a subgroup we will perform whole genome sequencing of bi-sulfite concerted DNA to yield a complete map of methylation changes. The same patients and samples will be subjected to Whole transcriptome Shotgun Sequencing (WTSS) to yield a complete map of expression as well as RNA variants.

For more information about epigenetic analysis, please visit: www.diagenode.com