A unifying model that explains the origins of human inverted copy number variants.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101239074 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7404 (Electronic) Linking ISSN: 15537390 NLM ISO Abbreviation: PLoS Genet Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, c2005-
    • Subject Terms:
      DNA Copy Number Variations*/genetics ; Homologous Recombination*; Humans ; Base Sequence ; DNA Replication/genetics ; Inverted Repeat Sequences
    • Abstract:
      With the release of the telomere-to-telomere human genome sequence and the availability of both long-read sequencing and optical genome mapping techniques, the identification of copy number variants (CNVs) and other structural variants is providing new insights into human genetic disease. Different mechanisms have been proposed to account for the novel junctions in these complex architectures, including aberrant forms of DNA replication, non-allelic homologous recombination, and various pathways that repair DNA breaks. Here, we have focused on a set of structural variants that include an inverted segment and propose that they share a common initiating event: an inverted triplication with long, unstable palindromic junctions. The secondary rearrangement of these palindromes gives rise to the various forms of inverted structural variants. We postulate that this same mechanism (ODIRA: origin-dependent inverted-repeat amplification) that creates the inverted CNVs in inherited syndromes also generates the palindromes found in cancers.
      Competing Interests: The authors have declared that no competing interests exist.

      (Copyright: © 2024 Brewer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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    • Grant Information:
      R01 GM018926 United States GM NIGMS NIH HHS; R01 GM147040 United States GM NIGMS NIH HHS; R35 GM122497 United States GM NIGMS NIH HHS
    • Publication Date:
      Date Created: 20240104 Date Completed: 20240108 Latest Revision: 20241019
    • Publication Date:
      20241019
    • Accession Number:
      PMC10766186
    • Accession Number:
      10.1371/journal.pgen.1011091
    • Accession Number:
      38175827