Early postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pair

dc.citation.epage459en_US
dc.citation.issueNumber7en_US
dc.citation.spage455en_US
dc.citation.volumeNumber51en_US
dc.contributor.authorDal, G. M.en_US
dc.contributor.authorErgüner, B.en_US
dc.contributor.authorSaǧıroǧlu, M. S.en_US
dc.contributor.authorYüksel, B.en_US
dc.contributor.authorOnat, O. E.en_US
dc.contributor.authorAlkan C.en_US
dc.contributor.authorÖzçelik, T.en_US
dc.date.accessioned2016-02-08T10:59:17Z
dc.date.available2016-02-08T10:59:17Z
dc.date.issued2014en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.departmentDepartment of Computer Engineeringen_US
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.description.abstractBackground: Human de novo single-nucleotide variation (SNV) rate is estimated to range between 0.82-1.70×10-8 mutations per base per generation. However, contribution of early postzygotic mutations to the overall human de novo SNV rate is unknown. Methods: We performed deep whole-genome sequencing (more than 30-fold coverage per individual) of the whole-blood-derived DNA samples of a healthy monozygotic twin pair and their parents. We examined the genotypes of each individual simultaneously for each of the SNVs and discovered de novo SNVs regarding the timing of mutagenesis. Putative de novo SNVs were validated using Sanger-based capillary sequencing. Results: We conservatively characterised 23 de novo SNVs shared by the twin pair, 8 de novo SNVs specific to twin I and 1 de novo SNV specific to twin II. Based on the number of de novo SNVs validated by Sanger sequencing and the number of callable bases of each twin, we calculated the overall de novo SNV rate of 1.31×10-8 and 1.01×10-8 for twin I and twin II, respectively. Of these, rates of the early postzygotic de novo SNVs were estimated to be 0.34×10-8 for twin I and 0.04×10-8 for twin II. Conclusions: Early postzygotic mutations constitute a substantial proportion of de novo mutations in humans. Therefore, genome mosaicism resulting from early mitotic events during embryogenesis is common and could substantially contribute to the development of diseases.en_US
dc.identifier.doi10.1136/jmedgenet-2013-102197en_US
dc.identifier.issn0022-2593
dc.identifier.urihttp://hdl.handle.net/11693/26399
dc.language.isoEnglishen_US
dc.publisherB M J Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1136/jmedgenet-2013-102197en_US
dc.source.titleJournal of Medical Geneticsen_US
dc.subjectDNAen_US
dc.subjectAdulten_US
dc.subjectControlled studyen_US
dc.subjectDNA isolationen_US
dc.subjectFemaleen_US
dc.subjectGene frequencyen_US
dc.subjectGene mappingen_US
dc.subjectGene sequenceen_US
dc.subjectGenetic proceduresen_US
dc.subjectGenetic variabilityen_US
dc.subjectGenome analysisen_US
dc.subjectGenotypeen_US
dc.subjectHumanen_US
dc.subjectHuman experimenten_US
dc.subjectIndel mutationen_US
dc.subjectMaleen_US
dc.subjectMiddle ageden_US
dc.subjectMitosisen_US
dc.subjectMonozygotic twinsen_US
dc.subjectMutagenesisen_US
dc.subjectMutation rateen_US
dc.subjectNormal humanen_US
dc.subjectParenten_US
dc.subjectPriority journalen_US
dc.subjectReference allele frequencyen_US
dc.subjectSanger sequencingen_US
dc.subjectSingle nucleotide polymorphismen_US
dc.subjectSingle nucleotide variationen_US
dc.subjectYoung adulten_US
dc.subjectDNA sequenceen_US
dc.subjectTwinsen_US
dc.titleEarly postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pairen_US
dc.typeArticleen_US
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