Identifier PRJCA000393
Title Targeted sequencing and functional analysis reveal a potentially shared pathogenesis in autism spectrum disorders
Project data type Variation
Organism Homo sapiens
Description Autism spectrum disorder (ASD) represents a set of complex neurodevelopmental disorders with large degrees of heritability and heterogeneity. We sequenced 136 microcephaly or macrocephaly (Mic-Mac)-related genes and 158 possible ASD-risk genes in 536 Chinese ASD probands and detected 22 damaging de novo mutations (DNMs) in 20 genes, including CHD8 and SCN2A, with recurrent events. Nine of the 20 genes were previously reported toreportedly harbour DNMs in ASD patients from other populations, and while 11 genes of them were first identified here for the first timein present study. We combined genetic variations of the 294 sequenced genes from publicly available whole-exome or whole-genome sequencing studies (4,167 probands plus 1,786 controls) with our Chinese population (536 cases plus 1,457 controls) to optimize the power of candidate-gene prioritization. As a result, we prioritized 67 ASD-candidate genes that exhibited significantly higher probabilities of haploinsufficiency and genic intolerance, and significantly interacted and co-expressed with each another, as well as other known ASD-risk genes. Probands with DNMs or rare inherited mutations in the 67 candidate genes exhibited significantly lower intelligence quotients, supporting their strong functional impact. Additionally, we prioritized 39 ASD-related Mic-Mac-risk genes, and showed their that interactioned and co-expressed expression with each other, as well other known Mic-Mac- or ASD-risk genes, and formedin a functional network that converged on chromatin remodelling, synapse transmission, and cell cycle progression. Genes within the three functional subnetworks exhibited distinct and recognizable spatiotemporal-expression patterns in human brains and laminar-expression profiles in the developing neocortex, highlighting their important roles in brain development.
Sample scope Monoisolate
Release date 2017-03-25
Submitter Jinchen  Li  (
Affiliation Central South University
Submission date 2017-03-25

Project Data

Resource name Description
BioSample (1) -
SAMC012451 Autism
GSA (1) -
CRA000220 CRA000220