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11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome

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dc.contributor.author El Maarri, Osman
dc.contributor.author Schreiner, Felix
dc.contributor.author Gohlke, Bettina
dc.contributor.author Stutte, Sonja
dc.contributor.author Bartmann, Peter
dc.contributor.author Hecher, Kurt
dc.contributor.author Oldenburg, Johannes
dc.contributor.author Woelfle, Joachim
dc.date.accessioned 2017-09-14T12:49:01Z
dc.date.available 2017-09-14T12:49:01Z
dc.date.copyright 2013 en_US
dc.identifier.issn 1868-7083 en_US
dc.identifier.uri http://hdl.handle.net/10725/6195
dc.description.abstract Background Prenatal growth restriction and low birth weight have been linked to long-term alterations of health, presumably via adaptive modifications of the epigenome. Recent studies indicate a plasticity of the 11p15 epigenotype in response to environmental changes during early stages of human development. Study design We analyzed methylation levels at different 11p15 loci in 20 growth-discordant monozygotic twin pairs. Intrauterine development was discordant due to severe twin-to-twin transfusion syndrome (TTTS), which was treated by fetoscopic laser coagulation of communicating vessels before 25 weeks of gestation. Methylation levels at age 4 were determined in blood and buccal cell-derived DNA by the single nucleotide primer extension reaction ion pair reverse-phase high performance liquid chromatography (SNuPE IP RP HPLC) assay. Methylation at LINE-1 repeats was analyzed as an estimate of global methylation. Results In general, variance of locus-specific methylation levels appeared to be higher in buccal cell- as compared to blood cell-derived DNA samples. Paired analyses within the twin pairs revealed significant differences at only one CpG site (IGF2 dmr0 SN3 (blood), +1.9% in donors; P = 0.013). When plotting the twin pair-discordance in birth weight against the degree of discordance in site-specific methylation at age 4, only a few CpGs were found to interact (one CpG site each at IGF2dmr0 in blood/saliva DNA, one CpG at LINE-1 repeats in saliva DNA), with 26 to 36% of the intra-twin pair divergence at these sites explained by prenatal growth discordance. However, across the entire cohort of 40 children, site-specific methylation did not correlate with SD-scores for weight or length at birth. Insulin-like growth factor-II serum concentrations showed significant within-twin pair correlations at birth (R = 0.57) and at age 4 (R = 0.79), but did not differ between donors and recipients. They also did not correlate with the analyzed 11p15 methylation parameters. Conclusion In a cohort of 20 growth-discordant monozygotic twin pairs, severe alteration in placental blood supply due to TTTS appears to leave only weak, if any, epigenetic marks at the analyzed CpG sites at 11p15. en_US
dc.language.iso en en_US
dc.title 11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 201508713 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Clinical Epigenetics en_US
dc.journal.volume 6 en_US
dc.journal.issue 6 en_US
dc.identifier.doi https://doi.org/10.1186/1868-7083-6-6 en_US
dc.identifier.ctation Schreiner, F., Gohlke, B., Stutte, S., Bartmann, P., Hecher, K., Oldenburg, J., ... & Woelfle, J. (2014). 11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine development due to severe twin-to-twin transfusion syndrome. Clinical epigenetics, 6(1), 6. en_US
dc.author.email osman.elmaarri@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/1868-7083-6-6 en_US
dc.author.affiliation Lebanese American University en_US


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