TY - JOUR
T1 - A novel strategy combining array-CGH, whole-exome sequencing and in utero electroporation in rodents to identify causative genes for brain malformations
AU - Conti, Valerio
AU - Carabalona, Aurelie
AU - Pallesi-Pocachard, Emilie
AU - Leventer, Richard J.
AU - Schaller, Fabienne
AU - Parrini, Elena
AU - Deparis, Agathe A.
AU - Watrin, Françoise
AU - Buhler, Emmanuelle
AU - Novara, Francesca
AU - Lise, Stefano
AU - Pagnamenta, Alistair T.
AU - Kini, Usha
AU - Taylor, Jenny C.
AU - Zuffardi, Orsetta
AU - Represa, Alfonso
AU - Keays, David Antony
AU - Guerrini, Renzo
AU - Falace, Antonio
AU - Cardoso, Carlos
N1 - Extracted concepts
Malformations of Cortical Development
Genes
Neuroimaging
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - Animal model
KW - Array-CGH
KW - In utero electroporation
KW - Issue 130
KW - Malformations of cortical development
KW - Neuroscience
KW - RNA interference
KW - Whole-exome sequencing
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U2 - 10.3791/53570
DO - 10.3791/53570
M3 - Article
AN - SCOPUS:85037616647
VL - 2017
JO - Journal of Visualized Experiments
JF - Journal of Visualized Experiments
SN - 1940-087X
IS - 130
M1 - e53570
ER -