A unifying model that explains the origins of human inverted copy number variants.
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...
| Những tác giả chính: | , , |
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| Định dạng: | Bài viết |
| Ngôn ngữ: | English |
| Được phát hành: |
Public Library of Science (PLoS)
2024-01-01
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| Loạt: | PLoS Genetics |
| Truy cập trực tuyến: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1011091&type=printable |
| _version_ | 1827059334062800896 |
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| author | Bonita J Brewer Maitreya J Dunham M K Raghuraman |
| author_facet | Bonita J Brewer Maitreya J Dunham M K Raghuraman |
| author_sort | Bonita J Brewer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T02:00:21Z |
| format | Article |
| id | doaj.art-f4ac5e5b8cc9472c8d2bc8fb7d6b64fa |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2025-02-18T18:39:15Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-f4ac5e5b8cc9472c8d2bc8fb7d6b64fa2024-10-21T05:31:42ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042024-01-01201e101109110.1371/journal.pgen.1011091A unifying model that explains the origins of human inverted copy number variants.Bonita J BrewerMaitreya J DunhamM K RaghuramanWith 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1011091&type=printable |
| spellingShingle | Bonita J Brewer Maitreya J Dunham M K Raghuraman A unifying model that explains the origins of human inverted copy number variants. PLoS Genetics |
| title | A unifying model that explains the origins of human inverted copy number variants. |
| title_full | A unifying model that explains the origins of human inverted copy number variants. |
| title_fullStr | A unifying model that explains the origins of human inverted copy number variants. |
| title_full_unstemmed | A unifying model that explains the origins of human inverted copy number variants. |
| title_short | A unifying model that explains the origins of human inverted copy number variants. |
| title_sort | unifying model that explains the origins of human inverted copy number variants |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1011091&type=printable |
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