• Etude génétique du complexe synaptique lié au récepteur NMDA et caractérisation de modèles à complexité variable dans l'autisme ( PDF , 36364166 kB )

Autism is a developmental disorder of the central nervous system defined by impairments in social interaction and communication, and by restricted and repetitive behavior. Its prevalence is currently estimated at around 1% in the general population. Autism is characterized by a wide heterogeneity at both phenotypic and genetic level. To date, more than 300 candidate genes were characterized either by copy number variations (CNV) and/or nucleotide variations (SNV). Their identification has highlighted a significant contribution of de novo mutations, as well as the involvement of targeted pathophysiological pathways, particularly post-synaptic density (PSD). The work of this thesis was to perform a global genetic study of about 100 autistic individuals representing 88 families, in order to assess both the contribution of CNV by high-resolution pangenomic CGH array and secondly to identify mutations among 216 genes coding protein from post-synaptic complex bound to NMDA receptor (NRC/MASC), with high-throughput targeted sequencing. This complementary approach allowed us to identify new candidate genes and regions, or reproduce their involvement in autism. Our results further demonstrate that the presence of genetic model that involve interactions between de novo and/or rarely inherited are found specifically associated with autism and absent in the intellectual disability. Keywords: Autism, copy number variations, post-synaptic proteome, multi-hit genetic model, high-throughput sequencingAutism is a developmental disorder of the central nervous system defined by impairments in social interaction and communication, and by restricted and repetitive behavior. Its prevalence is currently estimated at around 1% in the general population. Autism is characterized by a wide heterogeneity at both phenotypic and genetic level. To date, more than 300 candidate genes were characterized either by copy number variations (CNV) and/or nucleotide variations (SNV). Their identification has highlighted a significant contribution of de novo mutations, as well as the involvement of targeted pathophysiological pathways, particularly post-synaptic density (PSD).

• Dates
  Created on March 31, 2015