ABCP Webinar: Decoding autism – insights from Chinese ASD cohorts

Title

Decoding autism – insights from Chinese ASD cohorts

Speaker

Professor Zilong Qiu (仇子龙研究员), Center for Excellence in Brain Science and Intelligence Technology (Institute of Neuroscience), Chinese Academy of Science, Shanghai, China

Language

The talk will be delivered in English.

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder causing impairments in social communication and stereotypical behaviors, often with developmental delay or intellectual disabilities (DD/ID). Accruing evidence indicates that ASD is highly heritable and genome-wide studies on ASD cohorts have defined numerous genetic contributors. Notably, since most of these studies have been performed with individuals of European and Hispanic ancestries, thus there is a paucity of genetic analyses of ASD in the East Asian population. Here, we performed whole-exome sequencing on 772 Chinese ASD trios, combining with a previous 369 ASD trios, to identify de novo variants in 1141 ASD trios. We found that ASD without DD/ID carried less disruptive de novo variants than ASD with DD/ID. Surprisingly, we found that expression of genes with de novo variants in ASD without DD/ID were enriched in a subtype of human neural progenitor cells. Importantly, some ASD risk genes identified in this study are not present in the current ASD gene database, suggesting that there may be unique genetic contributors to ASD with the East Asian ancestry. We validated one such novel ASD candidate gene – SLC35G1 by showing that mice harboring heterozygous deletion of Slc35g1 exhibited defects in social interaction behaviors. Together, this work nominates novel ASD candidate genes and suggests that genome-wide genetic studies in ASD cohorts of different ancestries are essential to reveal the comprehensive genetic architecture of ASD.

Bio of Speaker

Professor Zilong Qiu got his bachelor degree in 1998 from Shanghai Jiao Tong University in Shanghai, and received his PhD degree from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences in 2003. From 2003 to 2009, he did his postdoctoral fellow in Dr Anirvan Ghosh’s lab at the University of California, San Diego, US. He joined the Institute of Neuroscience in July 2009 as Principal Investigator and the Head of the Laboratory of Molecular Basis of Neural Plasticity. His major research interests are molecular basis of neural plasticity.

仇子龙研究员从事自闭症、瑞特综合征等神经发育疾病的生物学研究，研究成果阐述了神经发育疾病的遗传、分子与神经环路机制，并建立了自闭症的非人灵长类动物模型。自闭症的非人灵长类动物模型工作入选科技部2016年“中国科学十大进展”，中国科协2016年“中国生命科学十大进展”。

仇子龙研究员课题组长期受中科院、科技部、国家基金委等项目资助。仇子龙研究员于2016年获中科院上海分院杰出青年科技创新人才奖，2016年获国家基金委“杰出青年”科学基金，2017年获药明康德生命化学研究奖，2017年任中科院特聘研究员，2018年晋升中科院神经所高级研究员，2018年入选科技部“中青年科技创新领军人才”，2019年入选中组部“万人计划“与上海市优秀学术带头人。

仇子龙研究员还长期致力于自闭症与生命科学的科普工作，与知识分子、果壳网公众号等科普新媒体长期合作，撰写了大量自闭症与生命科学方面的科普文章，多次参加中科院SELF、墨子沙龙、一席、造就、上海科普大讲坛等科普活动，荣获2018年上海市科普教育创新二等奖与上海市科技系统优秀志愿者称号，2020年获得全国科普工作先进工作者称号。

Selected Publications:

• Yang, K., Shi, Y., Du, X., Wang, J., Zhang, Y., Shan, S., Yuan, Y., Wang, R., Zhou, C., Liu, Y., Cai, Z., Wang, Y., Fan, L., Xu, H., Yu, J., Cheng, J., Li, F., Qiu, Z. (2021) SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice. Cell Reports 37,109939
• Wu, S., Li, X., Qin, D., Zhang, L., Cheng, T., Chen, Z., Nie, B., Ren, X., Wu, J., Wang, W., Hu, Y., Gu, Y., Lv, L., Yin, Y., Hu,X., Qiu, Z. (2020) Induction of core symptoms of autism spectrum disorders by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys. Science Bulletin. 66:937-946
• Li, S., Yuan, B., Cao, J., Chen, J., Chen, J., Qiu, J., Zhao, X., Wang, X., Qiu, Z., Cheng, T. (2020) Docking sites inside Cas9 for adenine base editing diversification and RNA off-target elimination. Nature Communications11(1):5827
• Cheng, T., Li, S., Yuan, B., Wang, X., Zhou, W., Qiu, Z. (2019) Expanding C–T base editing toolkit with diversified cytidine deaminases. Nature Communications10: 3612
• Cai, Y., Cheng, T.L., Yao, Y., Li, X., Ma, Y., Bao, J., Li, L., Zhao, H., Zhang, M., Qiu, Z, Xue, T. (2019) In vivo genome editing rescues photoreceptor degeneration via a Cas9/RecA-mediated homology-directed repair pathway. Science Advances 5(4):eaav3335
• Li, X., Yu, B., Sun, Q., Zhang, Y., Ren, M., Zhang, X., Li, A., Yuan, J., Madisen, L., Luo, Q., Zeng, H., Gong, H., Qiu, Z. (2018) Generation of a whole-brain atlas for the cholinergic system and mesoscopic projectome analysis of basal forebrain cholinergic neurons. Proc Natl Acad Sci USA. 115(2):415-420
• Dang, T., Duan, W., Yu, B., Tong, D.L., Cheng, C., Zhang, Y.F., Wu, W., Ye, K., Zhang, W.X., Wu, M., Wu, B., An, Y., Qiu, Z., Wu, B.L. (2018) Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development. Molecular Psychiatry23(3):747-758
• Qiu, Z. (2018) Deciphering MECP2 – associated disorders: disrupted circuits and the hope for repair. Current Opinion in Neurobiology 48:30-36 (Invited review)
• Wen, Z., Cheng, T.L., Li, G.Z., Sun, S.B., Yu, S.Y., Zhang, Y., Du, Y.S., Qiu, Z. (2017) Identification of Autism-Related MECP2 Mutations by Whole-Exome Sequencing and Functional Validation. Molecular Autism 8:43
• Yang, K., Yu, B., Cheng, C., Cheng, T.L., Yuan, B., Li, K., Xiao, J.H., Qiu, Z., Zhou, Y.X. (2017) Mir505-3p regulates axonal development via inhibiting autophagy pathway by targeting Atg12. Autophagy 13:1679-1696
• Liu, Z., Li, X., Zhang, J., Cai, Y., Cheng, T., Cheng, C., Wang, Y., Zhang, C., Nie, Yan., Chen, Z., Bian, W., Zhang, L., Xiao, J., Lu, B., Zhang, Y., Zhang., X., Sang, X., Wu, J., Xu, X., Xiong, Z., Zhang, F., Yu, X., Gong, N., Zhou, W., Sun, Q., Qiu, Z. (2016) Autism-like behaviors and germline transmission in transgenic monkeys overexpressing MeCP2. Nature. 530:98-102
• Cheng, T., Wang, Z., Liao, Q., Zhu, Y., Zhou, W., Xu, W., Qiu, Z. (2014) MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex. Developmental Cell 28:547-560

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