title: Whole genome and exome sequencing of monozygotic twins discordant for Crohn's disease.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstrasse 12, 24105 Kiel, Germany. b.petersen@ikmb.uni-kiel.de.
authors.forename: Britt-Sabina
authors.initials: BS
authors.lastname: Petersen
authors.forename: Martina E
authors.initials: ME
authors.lastname: Spehlmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Raedler
authors.forename: Björn
authors.initials: B
authors.lastname: Stade
authors.forename: Ingo
authors.initials: I
authors.lastname: Thomsen
authors.forename: Raquel
authors.initials: R
authors.lastname: Rabionet
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
mesh_terms: D000328:Adult; D001483:Base Sequence; D003424:Crohn Disease / Q000235:genetics*; D056915:DNA Copy Number Variations; D059472:Exome; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014430:Twins, Monozygotic / Q000235:genetics*