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      • Department of Molecular Biology and Genetics
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      Early postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pair

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      Author(s)
      Dal, G. M.
      Ergüner, B.
      Saǧıroǧlu, M. S.
      Yüksel, B.
      Onat, O. E.
      Alkan C.
      Özçelik, T.
      Date
      2014
      Source Title
      Journal of Medical Genetics
      Print ISSN
      0022-2593
      Publisher
      B M J Group
      Volume
      51
      Issue
      7
      Pages
      455 - 459
      Language
      English
      Type
      Article
      Item Usage Stats
      230
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      277
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      Abstract
      Background: 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.
      Keywords
      DNA
      Adult
      Controlled study
      DNA isolation
      Female
      Gene frequency
      Gene mapping
      Gene sequence
      Genetic procedures
      Genetic variability
      Genome analysis
      Genotype
      Human
      Human experiment
      Indel mutation
      Male
      Middle aged
      Mitosis
      Monozygotic twins
      Mutagenesis
      Mutation rate
      Normal human
      Parent
      Priority journal
      Reference allele frequency
      Sanger sequencing
      Single nucleotide polymorphism
      Single nucleotide variation
      Young adult
      DNA sequence
      Twins
      Permalink
      http://hdl.handle.net/11693/26399
      Published Version (Please cite this version)
      http://dx.doi.org/10.1136/jmedgenet-2013-102197
      Collections
      • Department of Computer Engineering 1561
      • Department of Molecular Biology and Genetics 542
      • Institute of Materials Science and Nanotechnology (UNAM) 2258
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