Functional landscape of genome-wide postzygotic somatic mutations between monozygotic twins.

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    • Source:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 9423827 Publication Model: Print Cited Medium: Internet ISSN: 1756-1663 (Electronic) Linking ISSN: 13402838 NLM ISO Abbreviation: DNA Res Subsets: MEDLINE
    • Publication Information:
      Publication: 2006- : Oxford : Oxford University Press
      Original Publication: Tokyo, Japan : Kazusa DNA Research Institute ; Universal Academy Press [1994-
    • Subject Terms:
      Twins, Monozygotic*/genetics ; Whole Genome Sequencing* ; Mutation*; Humans ; Female ; Male ; Adult ; Genome, Human ; Middle Aged ; Gene Frequency ; Genotype
    • Abstract:
      Monozygotic (MZ) twins originate from a single fertilized egg, making them genetically identical at the time of conception. However, postzygotic somatic mutations (PZMs) can introduce genetic differences after separation. Although whole-genome sequencing (WGS) sheds light on somatic mutations in cancer genomics, its application in genomic studies of MZ twins remains limited. In this study, we investigate PZMs in 30 healthy MZ twin pairs from the Osaka University Center for Twin Research using WGS (average depth = 23.8) and a robust germline-calling algorithm. We find high genotype concordance rates (exceeding 99%) in MZ twins. We observe an enrichment of PZMs with variant allele frequency around 0.5 in twins with highly concordant genotypes. These PZMs accumulate more frequently in non-coding regions compared with protein-coding regions, which could potentially influence gene expression. No significant association is observed between the number of PZMs and age or sex. Direct sequencing confirms a missense mutation in the ANKRD35 gene among the PZMs. By applying a genome-wide mutational signature pattern technique, we detect an age-related clock-like signature in these early postzygotic somatic mutations in MZ twins. Our study provides insights that contribute to a deeper understanding of genetic variation in MZ twins.
      (© The Author(s) 2024. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)
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    • Contributed Indexing:
      Keywords: age-related clock-like mutational signature; monozygotic twin; postzygotic somatic mutation; twin research; whole-genome sequencing
    • Publication Date:
      Date Created: 20240922 Date Completed: 20241014 Latest Revision: 20241016
    • Publication Date:
      20241016
    • Accession Number:
      PMC11472055
    • Accession Number:
      10.1093/dnares/dsae028
    • Accession Number:
      39306676