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Disruption of human-specific synaptogenesis program in autism [RNA-seq]

ABSTRACT: Disruption of human-specific synaptogenesis program in autism [RNA-seq]

OTHER RELATED OMICS DATASETS IN: GSE59288

PROVIDER: PRJNA254971 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1510130.fastq.gz	Fastqsanger.gz
	SRR1510140.fastq.gz	Fastqsanger.gz
	SRR1510150.fastq.gz	Fastqsanger.gz
	SRR1510160.fastq.gz	Fastqsanger.gz
	SRR1510170.fastq.gz	Fastqsanger.gz

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Disruption of human-specific synaptogenesis program in autism [RNA-seq]

Project description:To test the connection between the molecular mechanisms underlying autistic disorder and human cognitive evolution, we analyzed the gene expression changes taking place during prefrontal cortex development in autism patients and healthy controls, as well as non-human primates. We found the genes with expression changes in autism are significantly overlapped with genes showing human-specific developmental profile. A major pattern of the overlapped genes reflects the aberrant acceleration of synaptogenesis and synaptic maturation followed by premature synaptic pruning in the prefrontal cortex of autism patients. This pattern involves the same developmental program that controls human-specific extension of cortical synaptogenesis in healthy individuals. Taken together, these findings shed light on the molecular mechanisms underlying autistic phenotype and provide potential targets for clinical intervention.

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Project description:Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with = 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. Keywords: Autism spectrum disorder, Affymetrix SNP genotyping, linkage analysis, copy number analysis, chromosomal rearrangements.

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