Targeted correction of megabase-scale CNTN6 duplication in induced pluripotent stem cells and impacts on gene expression
Copy number variations of the human CNTN6 gene, resulting from megabase-scale microdeletions or microduplications in the 3p26.3 region, are frequently implicated in neurodevelopmental disorders such as intellectual disability and developmental delay. However, duplication of the full-length human CNT...
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PeerJ Inc.
2025-01-01
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| author | Maria Gridina Polina Orlova Oleg Serov |
| author_facet | Maria Gridina Polina Orlova Oleg Serov |
| author_sort | Maria Gridina |
| collection | DOAJ |
| description | Copy number variations of the human CNTN6 gene, resulting from megabase-scale microdeletions or microduplications in the 3p26.3 region, are frequently implicated in neurodevelopmental disorders such as intellectual disability and developmental delay. However, duplication of the full-length human CNTN6 gene presents with variable penetrance, resulting in phenotypes that range from neurodevelopmental disorders to no visible pathologies, even within the same family. Previously, we obtained a set of induced pluripotent stem cell lines derived from a patient with a CNTN6 gene duplication and from two healthy donors. Our findings demonstrated that CNTN6 expression in neurons carrying the duplication was significantly reduced. Additionally, the expression from the CNTN6 duplicated allele was markedly lower compared to the wild-type allele. Here, we first introduce a system for correcting megabase-scale duplications in induced pluripotent stem cells and secondly analyze the impact of this correction on CNTN6 gene expression. We showed that the deletion of one copy of the CNTN6 duplication did not affect the expression levels of the remaining allele in the neuronal cells. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-5d223188666449ad99aa1725581b1dad2025-01-22T15:05:14ZengPeerJ Inc.PeerJ2167-83592025-01-0113e1856710.7717/peerj.18567Targeted correction of megabase-scale CNTN6 duplication in induced pluripotent stem cells and impacts on gene expressionMaria Gridina0Polina Orlova1Oleg Serov2Genomic Mechanisms of Ontogenesis, Institute of Cytology and Genetics, Novosibirsk, Novosibirsk, RussiaGenomic Mechanisms of Ontogenesis, Institute of Cytology and Genetics, Novosibirsk, Novosibirsk, RussiaGenomic Mechanisms of Ontogenesis, Institute of Cytology and Genetics, Novosibirsk, Novosibirsk, RussiaCopy number variations of the human CNTN6 gene, resulting from megabase-scale microdeletions or microduplications in the 3p26.3 region, are frequently implicated in neurodevelopmental disorders such as intellectual disability and developmental delay. However, duplication of the full-length human CNTN6 gene presents with variable penetrance, resulting in phenotypes that range from neurodevelopmental disorders to no visible pathologies, even within the same family. Previously, we obtained a set of induced pluripotent stem cell lines derived from a patient with a CNTN6 gene duplication and from two healthy donors. Our findings demonstrated that CNTN6 expression in neurons carrying the duplication was significantly reduced. Additionally, the expression from the CNTN6 duplicated allele was markedly lower compared to the wild-type allele. Here, we first introduce a system for correcting megabase-scale duplications in induced pluripotent stem cells and secondly analyze the impact of this correction on CNTN6 gene expression. We showed that the deletion of one copy of the CNTN6 duplication did not affect the expression levels of the remaining allele in the neuronal cells.https://peerj.com/articles/18567.pdfCRISPR/Cas9-mediated genome editingCre/loxP systemDuplicationCNTN6Differentiation of induced pluripotent stem cellsInduced pluripotent stem cells |
| spellingShingle | Maria Gridina Polina Orlova Oleg Serov Targeted correction of megabase-scale CNTN6 duplication in induced pluripotent stem cells and impacts on gene expression PeerJ CRISPR/Cas9-mediated genome editing Cre/loxP system Duplication CNTN6 Differentiation of induced pluripotent stem cells Induced pluripotent stem cells |
| title | Targeted correction of megabase-scale CNTN6 duplication in induced pluripotent stem cells and impacts on gene expression |
| title_full | Targeted correction of megabase-scale CNTN6 duplication in induced pluripotent stem cells and impacts on gene expression |
| title_fullStr | Targeted correction of megabase-scale CNTN6 duplication in induced pluripotent stem cells and impacts on gene expression |
| title_full_unstemmed | Targeted correction of megabase-scale CNTN6 duplication in induced pluripotent stem cells and impacts on gene expression |
| title_short | Targeted correction of megabase-scale CNTN6 duplication in induced pluripotent stem cells and impacts on gene expression |
| title_sort | targeted correction of megabase scale cntn6 duplication in induced pluripotent stem cells and impacts on gene expression |
| topic | CRISPR/Cas9-mediated genome editing Cre/loxP system Duplication CNTN6 Differentiation of induced pluripotent stem cells Induced pluripotent stem cells |
| url | https://peerj.com/articles/18567.pdf |
| work_keys_str_mv | AT mariagridina targetedcorrectionofmegabasescalecntn6duplicationininducedpluripotentstemcellsandimpactsongeneexpression AT polinaorlova targetedcorrectionofmegabasescalecntn6duplicationininducedpluripotentstemcellsandimpactsongeneexpression AT olegserov targetedcorrectionofmegabasescalecntn6duplicationininducedpluripotentstemcellsandimpactsongeneexpression |