A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
| Autor: | Carlos Cardoso, Jenny C. Taylor, David Antony Keays, Alistair T. Pagnamenta, Valerio Conti, Antonio Falace, Françoise Watrin, Francesca Novara, Emilie Pallesi-Pocachard, Agathe A. Deparis, Renzo Guerrini, Aurelie Carabalona, Alfonso Represa, Emmanuelle Buhler, Elena Parrini, Orsetta Zuffardi, Richard J. Leventer, Stefano Lise, Usha Kini, Fabienne Schaller |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetics Candidate gene General Immunology and Microbiology General Chemical Engineering General Neuroscience Electroporation Biology medicine.disease Phenotype General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Epilepsy 030104 developmental biology 0302 clinical medicine Neuroimaging RNA interference medicine Gene 030217 neurology & neurosurgery Exome sequencing |
| Zdroj: | Journal of Visualized Experiments. |
| ISSN: | 1940-087X |
| DOI: | 10.3791/53570 |
| Popis: | Birth defects that involve the cerebral cortex - also known as malformations of cortical development (MCD) - are important causes of intellectual disability and account for 20-40% of drug-resistant epilepsy in childhood. High-resolution brain imaging has facilitated in vivo identification of a large group of MCD phenotypes. Despite the advances in brain imaging, genomic analysis and generation of animal models, a straightforward workflow to systematically prioritize candidate genes and to test functional effects of putative mutations is missing. To overcome this problem, an experimental strategy enabling the identification of novel causative genes for MCD was developed and validated. This strategy is based on identifying candidate genomic regions or genes via array-CGH or whole-exome sequencing and characterizing the effects of their inactivation or of overexpression of specific mutations in developing rodent brains via in utero electroporation. This approach led to the identification of the C6orf70 gene, encoding for a putative vesicular protein, to the pathogenesis of periventricular nodular heterotopia, a MCD caused by defective neuronal migration. |
| Databáze: | OpenAIRE |
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