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Whole genome and exome sequencing of monozygotic twins discordant for Crohn’s disease

Britt-Sabina Petersen1*, Martina E Spehlmann2, Andreas Raedler3, Björn Stade1, Ingo Thomsen1, Raquel Rabionet4, Philip Rosenstiel1, Stefan Schreiber2 and Andre Franke1

Author Affiliations

1 Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstrasse 12, 24105 Kiel, Germany

2 Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany

3 Department of Internal Medicine II, Gastroenterology, Asklepios Westklinikum Hamburg, Hamburg, Germany

4 Genomics and Disease Group, Center for Genomic Regulation, Barcelona, Spain

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BMC Genomics 2014, 15:564  doi:10.1186/1471-2164-15-564

Published: 5 July 2014



Crohn’s disease (CD) is an inflammatory bowel disease caused by genetic and environmental factors. More than 160 susceptibility loci have been identified for IBD, yet a large part of the genetic variance remains unexplained. Recent studies have demonstrated genetic differences between monozygotic twins, who were long thought to be genetically completely identical.


We aimed to test if somatic mutations play a role in CD etiology by sequencing the genomes and exomes of directly affected tissue from the bowel and blood samples of one and the blood-derived exomes of two further monozygotic discordant twin pairs. Our goal was the identification of mutations present only in the affected twins, pointing to novel candidates for CD susceptibility loci. We present a thorough genetic characterization of the sequenced individuals but detected no consistent differences within the twin pairs. An estimate of the CD susceptibility based on known CD loci however hinted at a higher mutational load in all three twin pairs compared to 1,920 healthy individuals.


Somatic mosaicism does not seem to play a role in the discordance of monozygotic CD twins. Our study constitutes the first to perform whole genome sequencing for CD twins and therefore provides a valuable reference dataset for future studies. We present an example framework for mosaicism detection and point to the challenges in these types of analyses.

Crohn’s disease; Discordant monozygotic twins; Somatic mosaicism; Whole genome sequencing; Exome sequencing