Chimeric Genes in Deletions and Duplications Associated with Intellectual Disability
We report on three nonrelated patients with intellectual disability and CNVs that give rise to three new chimeric genes. All the genes forming these fusion transcripts may have an important role in central nervous system development and/or in gene expression regulation, and therefore not only their...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | International Journal of Genomics |
| Online Access: | http://dx.doi.org/10.1155/2017/4798474 |
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| author | Sonia Mayo Sandra Monfort Mónica Roselló Carmen Orellana Silvestre Oltra Alfonso Caro-Llopis Francisco Martínez |
| author_facet | Sonia Mayo Sandra Monfort Mónica Roselló Carmen Orellana Silvestre Oltra Alfonso Caro-Llopis Francisco Martínez |
| author_sort | Sonia Mayo |
| collection | DOAJ |
| description | We report on three nonrelated patients with intellectual disability and CNVs that give rise to three new chimeric genes. All the genes forming these fusion transcripts may have an important role in central nervous system development and/or in gene expression regulation, and therefore not only their deletion or duplication but also the resulting chimeric gene may contribute to the phenotype of the patients. Deletions and duplications are usually pathogenic when affecting dose-sensitive genes. Alternatively, a chimeric gene may also be pathogenic by different gain-of-function mechanisms that are not restricted to dose-sensitive genes: the emergence of a new polypeptide that combines functional domains from two different genes, the deregulated expression of any coding sequence by the promoter region of a neighboring gene, and/or a putative dominant-negative effect due to the preservation of functional domains of partially truncated proteins. Fusion oncogenes are well known, but in other pathologies, the search for chimeric genes is disregarded. According to our findings, we hypothesize that the frequency of fusion transcripts may be much higher than suspected, and it should be taken into account in the array-CGH analyses of patients with intellectual disability. |
| format | Article |
| id | doaj-art-eaf800628ca6449ea44e5a63153b6b79 |
| institution | OA Journals |
| issn | 2314-436X 2314-4378 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Genomics |
| spelling | doaj-art-eaf800628ca6449ea44e5a63153b6b792025-08-20T02:22:02ZengWileyInternational Journal of Genomics2314-436X2314-43782017-01-01201710.1155/2017/47984744798474Chimeric Genes in Deletions and Duplications Associated with Intellectual DisabilitySonia Mayo0Sandra Monfort1Mónica Roselló2Carmen Orellana3Silvestre Oltra4Alfonso Caro-Llopis5Francisco Martínez6Unidad de Genética, Hospital Universitario y Politécnico La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia, SpainUnidad de Genética, Hospital Universitario y Politécnico La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia, SpainUnidad de Genética, Hospital Universitario y Politécnico La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia, SpainUnidad de Genética, Hospital Universitario y Politécnico La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia, SpainUnidad de Genética, Hospital Universitario y Politécnico La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia, SpainUnidad de Genética, Hospital Universitario y Politécnico La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia, SpainUnidad de Genética, Hospital Universitario y Politécnico La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia, SpainWe report on three nonrelated patients with intellectual disability and CNVs that give rise to three new chimeric genes. All the genes forming these fusion transcripts may have an important role in central nervous system development and/or in gene expression regulation, and therefore not only their deletion or duplication but also the resulting chimeric gene may contribute to the phenotype of the patients. Deletions and duplications are usually pathogenic when affecting dose-sensitive genes. Alternatively, a chimeric gene may also be pathogenic by different gain-of-function mechanisms that are not restricted to dose-sensitive genes: the emergence of a new polypeptide that combines functional domains from two different genes, the deregulated expression of any coding sequence by the promoter region of a neighboring gene, and/or a putative dominant-negative effect due to the preservation of functional domains of partially truncated proteins. Fusion oncogenes are well known, but in other pathologies, the search for chimeric genes is disregarded. According to our findings, we hypothesize that the frequency of fusion transcripts may be much higher than suspected, and it should be taken into account in the array-CGH analyses of patients with intellectual disability.http://dx.doi.org/10.1155/2017/4798474 |
| spellingShingle | Sonia Mayo Sandra Monfort Mónica Roselló Carmen Orellana Silvestre Oltra Alfonso Caro-Llopis Francisco Martínez Chimeric Genes in Deletions and Duplications Associated with Intellectual Disability International Journal of Genomics |
| title | Chimeric Genes in Deletions and Duplications Associated with Intellectual Disability |
| title_full | Chimeric Genes in Deletions and Duplications Associated with Intellectual Disability |
| title_fullStr | Chimeric Genes in Deletions and Duplications Associated with Intellectual Disability |
| title_full_unstemmed | Chimeric Genes in Deletions and Duplications Associated with Intellectual Disability |
| title_short | Chimeric Genes in Deletions and Duplications Associated with Intellectual Disability |
| title_sort | chimeric genes in deletions and duplications associated with intellectual disability |
| url | http://dx.doi.org/10.1155/2017/4798474 |
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