title: Whole-Exome Sequencing in Nine Monozygotic Discordant Twins.
abstract: By definition, monozygotic (MZ) twins carry an identical set of genetic information. The observation of early post-twinning mutational events was shown to cause phenotypic discordance among MZ twin pairs. These mutational events comprise genomic alterations at different scales, ranging from single nucleotide changes to larger copy-number variations (CNVs) of varying sizes, as well as epigenetic changes. Here, we performed whole-exome sequencing (WES) in nine discordant MZ twins to identify somatic mutational events in the affected twin that might exert a dominant negative effect. Five of these MZ twin pairs were discordant for congenital heart defects (CHD), two for endocrine disorders, one for omphalocele, and one for congenital diaphragmatic hernia (CDH). Analysis of WES data from all nine MZ twin pairs using the de novo probability tool DeNovoGear detected only one apparent de novo variation in TMPRSS13 in one of the CHD-affected twins. Analysis of WES data from all nine MZ twin pairs by using standard filter criteria without the de novo probability tool DeNovoGear revealed a total of 6,657 variations in which both the twin pairs differed. After filtering for variations only present in the affected twins and absent in in-house controls, 722 variations remained. Visual inspection for read quality decreased this number to 12, present only in the affected twin. However, Sanger sequencing of the overall 13 variations failed to confirm the variation in the affected twin. These results suggest that somatic mutational events in coding regions do not seem to play a major role in the phenotypic expression of MZ discordant twin pairs.
authors.affiliation: Institute of Human Genetics,University of Bonn,Bonn,Germany.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Cologne Center for Genomics,University of Cologne,Cologne,Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
authors.affiliation: Department of Neonatology,University of Bonn,Bonn,Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartmann
authors.affiliation: Institute of Human Genetics,University of Bonn,Bonn,Germany.
authors.forename: Alina C
authors.initials: AC
authors.lastname: Hilger
authors.affiliation: Department of Obstetrics and Prenatal Medicine,University of Bonn,Bonn,Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Berg
authors.affiliation: Department of Pediatric Cardiology,University of Bonn,Bonn,Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Herberg
authors.affiliation: Division of Endocrinology and Diabetes,Department of Medicine I,University of Bonn,Bonn,Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Klingmüller
authors.affiliation: Cologne Center for Genomics,University of Cologne,Cologne,Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.affiliation: Department of Clinical Chemistry and Clinical Pharmacology,University of Bonn,Bonn,Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.affiliation: Institute of Human Genetics,University of Bonn,Bonn,Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
mesh_terms: D056915:DNA Copy Number Variations; D004200:Diseases in Twins / Q000235:genetics*; D004700:Endocrine System Diseases / Q000235:genetics; D059472:Exome; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics; D006554:Hernia, Umbilical / Q000235:genetics; D065630:Hernias, Diaphragmatic, Congenital / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D014430:Twins, Monozygotic / Q000235:genetics*
keywords: discordance; monozygotic; twin pairs; whole-exome sequencing