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De Novo Gene Disruptions in Children on the Autistic Spectrum
- Source :
- Neuron. 74(2):285-299
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- SummaryExome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this differential and the number of recurrent and total targets of gene disruption found in our and similar studies, we estimate between 350 and 400 autism susceptibility genes. Many of the disrupted genes in these studies are associated with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders.
- Subjects :
- Male
Models, Molecular
Parents
Neuroscience(all)
Gene Dosage
SYNGAP1
Biology
medicine.disease_cause
Gene dosage
Fragile X Mental Retardation Protein
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Missense mutation
Genetic Predisposition to Disease
Child
Gene
Genetic Association Studies
Exome sequencing
030304 developmental biology
Family Health
Genetics
0303 health sciences
Mutation
General Neuroscience
medicine.disease
Phenotype
Child Development Disorders, Pervasive
Child, Preschool
Autism
Female
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 08966273
- Volume :
- 74
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Neuron
- Accession number :
- edsair.doi.dedup.....436dac00dfb388b306cc1884918b76cf
- Full Text :
- https://doi.org/10.1016/j.neuron.2012.04.009