首页|Identification of de novo Mutations in the Chinese Autism Spectrum Disorder Cohort via Whole-Exome Sequencing Unveils Brain Regions Implicated in Autism

Identification of de novo Mutations in the Chinese Autism Spectrum Disorder Cohort via Whole-Exome Sequencing Unveils Brain Regions Implicated in Autism

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Autism spectrum disorder(ASD)is a highly her-itable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors.Although hun-dreds of ASD risk genes,implicated in synaptic formation and transcriptional regulation,have been identified through human genetic studies,the East Asian ASD cohorts are still under-represented in genome-wide genetic studies.Here,we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin.Using a joint-calling analytical pipeline based on GATK toolkits,we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants,as well as de novo copy number variations containing known ASD-related genes.Importantly,combined with single-cell sequencing data from the developing human brain,we found that the expression of genes with de novo mutations was specifically enriched in the pre-,post-central gyrus(PRC,PC)and banks of the superior temporal(BST)regions in the human brain.By further analyzing the brain imaging data with ASD and healthy controls,we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls,suggesting the potential structural deficits associated with ASD.Finally,we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas,the insula,as well as the frontal lobes in ASD patients.This work indicated that combinatorial analysis with genome-wide screening,single-cell sequencing,and brain imaging data reveal the brain regions contributing to the etiology of ASD.

AutismCohortsWhole-exome sequencingSingle-cell sequencing

Bo Yuan、Mengdi Wang、Xinran Wu、Peipei Cheng、Ran Zhang、Shunying Yu、Jie Zhang、Yasong Du、Xiaoqun Wang、Zilong Qiu

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Institute of Neuroscience,State Key Laboratory of Neuroscience,CAS Center for Excellence in Brain Science and Intelligence Technology,Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology,Chinese Academy of Sciences,Shanghai 200032,China

Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

Institute of Science and Technology for Brain-Inspired Intelligence,Fudan University,Shanghai 200433,China

Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200032,China

Beijing Normal University,Beijing 100875,China

Songjiang Research Institute,Songjiang Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 201600,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaShanghai Brain-Intelligence Project from STCSMStrategic Priority Research Program of the Chinese Academy of SciencesProgram of Shanghai Academic Research LeaderOpen Large Infrastructure Research of the Chinese Academy of SciencesShanghai Municipal Science and Technology Major Project

3162501381941015320007266197308616JC1420501XDBS010602002018SHZDZX01

2023

10.1007/s12264-023-01037-6

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(10)
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