Dataset Information

Copy number detection in discordant monozygotic twins of Congenital Diaphragmatic Hernia (CDH) and Esophageal Atresia (EA) cohorts.

ABSTRACT: The occurrence of phenotypic differences between monozygotic (MZ) twins is commonly attributed to environmental factors, assuming that MZ twins have a complete identical genetic make-up. Yet, recently several lines of evidence showed that both genetic and epigenetic factors could have a role in phenotypic discordance after all. A high occurrence of copy number variation (CNV) differences was observed within MZ twin pairs discordant for Parkinson's disease, thereby stressing on the importance of post-zygotic mutations as disease-predisposing events. In this study, the prevalence of discrepant CNVs was analyzed in discordant MZ twins of the Esophageal Atresia (EA) and Congenital Diaphragmatic Hernia (CDH) cohort in the Netherlands. Blood-derived DNA from 11 pairs (7 EA and 4 CDH) was screened using high-resolution SNP arrays. Results showed an identical copy number profile in each twin pair. Mosaic chromosome gain or losses could not be detected either with a detection threshold of 20%. Some of the germ-line structural events demonstrated in five out of eleven twin pairs could function as a susceptible genetic background. For example, the 177-Kb loss of chromosome 10q26 in CDH pair-3 harbors the TCF7L2 gene (Tcf4 protein), which is implicated in the regulation of muscle fiber type development and maturation. In conclusion, discrepant CNVs are not a common cause of twin discordancy in these investigated congenital anomaly cohorts.

SUBMITTER: Veenma D

PROVIDER: S-EPMC3283183 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Copy number detection in discordant monozygotic twins of Congenital Diaphragmatic Hernia (CDH) and Esophageal Atresia (EA) cohorts.

Veenma Danielle D Brosens Erwin E de Jong Elisabeth E van de Ven Cees C Meeussen Connie C Cohen-Overbeek Titia T Boter Marjan M Eussen Hubertus H Douben Hannie H Tibboel Dick D de Klein Annelies A

European journal of human genetics : EJHG 20111109 3

The occurrence of phenotypic differences between monozygotic (MZ) twins is commonly attributed to environmental factors, assuming that MZ twins have a complete identical genetic make-up. Yet, recently several lines of evidence showed that both genetic and epigenetic factors could have a role in phenotypic discordance after all. A high occurrence of copy number variation (CNV) differences was observed within MZ twin pairs discordant for Parkinson's disease, thereby stressing on the importance of ...[more]

PMID: 22071887

Similar Datasets

Project description:BackgroundRheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes such as altered DNA methylation, which may also be influenced by genetic factors. To investigate possible contributions of DNA methylation to the aetiology of rheumatoid arthritis with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease-discordant monozygotic twin pairs.MethodsGenome-wide DNA methylation was assessed in 79 monozygotic twin pairs discordant for rheumatoid arthritis using the HumanMethylation450 BeadChip array (Illumina). Discordant twins were tested for both differential DNA methylation and methylation variability between rheumatoid arthritis and healthy twins. The methylation variability signature was then compared with methylation variants from studies of other autoimmune diseases and with an independent healthy population.ResultsWe have identified a differentially variable DNA methylation signature that suggests multiple stress response pathways may be involved in the aetiology of the disease. This methylation variability signature also highlighted potential epigenetic disruption of multiple RUNX3 transcription factor binding sites as being associated with disease development. Comparison with previously performed epigenome-wide association studies of rheumatoid arthritis and type 1 diabetes identified shared pathways for autoimmune disorders, suggesting that epigenetics plays a role in autoimmunity and offering the possibility of identifying new targets for intervention.ConclusionsThrough genome-wide analysis of DNA methylation in disease-discordant monozygotic twins, we have identified a differentially variable DNA methylation signature, in the absence of differential methylation in rheumatoid arthritis. This finding supports the importance of epigenetic variability as an emerging component in autoimmune disorders.

Dataset Information

Copy number detection in discordant monozygotic twins of Congenital Diaphragmatic Hernia (CDH) and Esophageal Atresia (EA) cohorts.

Publications

Copy number detection in discordant monozygotic twins of Congenital Diaphragmatic Hernia (CDH) and Esophageal Atresia (EA) cohorts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets