Jump to Main Content
Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing
- Wu, Jinyu, Yu, Ping, Jin, Xin, Xu, Xiu, Li, Jinchen, Li, Zhongshan, Wang, Mingbang, Wang, Tao, Wu, Xueli, Jiang, Yi, Cai, Wanshi, Mei, Junpu, Min, Qingjie, Xu, Qiong, Zhou, Bingrui, Guo, Hui, Wang, Ping, Zhou, Wenhao, Hu, Zhengmao, Li, Yingrui, Cai, Tao, Wang, Yi, Xia, Kun, Jiang, Yong-Hui, Sun, Zhong Sheng
- Journal of genetics and genomics 2018 v.45 no.10 pp. 527-538
- Chinese people, autism, chromatin, chromosome translocation, data collection, genes, genetic heterogeneity, genomics, inheritance (genetics), models, mutation, pathogenesis, risk, sequence analysis
- Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity. In this study, we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD, including de novo mutations, inherited variants, copy number variants (CNVs) and genomic structural variants. A higher mutation rate (Poisson test, P < 2.2 × 10−16) in exonic (1.37 × 10−8) and 3′-UTR regions (1.42 × 10−8) was revealed in comparison with that of whole genome (1.05 × 10−8). Using an integrated model, we identified 87 potentially risk genes (P < 0.01) from 4832 genes harboring various rare deleterious variants, including CHD8 and NRXN2, implying that the disorders may be in favor to multiple-hit. In particular, frequent rare inherited mutations of several microcephaly-associated genes (ASPM, WDR62, and ZNF335) were found in ASD. In chromosomal structure analyses, we found four de novo CNVs and one de novo chromosomal rearrangement event, including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1, which causes Angelman syndrome and microcephaly, and a disrupted TNR due to de novo chromosomal translocation t(1; 5)(q25.1; q33.2). Taken together, our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD. Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders, such as ASD, could provide novel insights into pathogenesis, diagnosis and treatment.