Genome-wide copy number variation analysis in a Chinese autism spectrum disorder cohort.

Guo H1,2, Peng Y1, Hu Z1, Li Y1, Xun G3, Ou J2, Sun L4, Xiong Z5, Liu Y1, Wang T1, Chen J1, Xia L1, Bai T1, Shen Y2, Tian Q1, Hu Y1, Shen L1, Zhao R1, Zhang X4, Zhang F2,6, Zhao J2, Zou X7, Xia K1,8,9.

Author information

Abstract

Autism spectrum disorder (ASD) describes a group of neurodevelopmental disorders with high heritability, although the underlying genetic determinants of ASDs remain largely unknown. Large-scale whole-genome studies of copy number variation in Han Chinese samples are still lacking. We performed a genome-wide copy number variation analysis of 343 ASD trios, 203 patients with sporadic cases and 988 controls in a Chinese population using Illumina genotyping platforms to identify CNVs and related genes that may contribute to ASD risk. We identified 32 rare CNVs larger than 1 Mb in 31 patients. ASD patients were found to carry a higher global burden of rare, large CNVs than controls. Recurrent de novo or case-private CNVs were found at 15q11-13, Xp22.3, 15q13.1-13.2, 3p26.3 and 2p12. The de novo 15q11-13 duplication was more prevalent in this Chinese population than in those with European ancestry. Several genes, including GRAMD2 and STAM, were implicated as novel ASD risk genes when integrating whole-genome CNVs and whole-exome sequencing data. We also identified several CNVs that include known ASD genes (SHANK3, CDH10, CSMD1) or genes involved in nervous system development (NYAP2, ST6GAL2, GRM6). Besides, our study also implicated Contactins-NYAPs-WAVE1 pathway in ASD pathogenesis. Our findings identify ASD-related CNVs in a Chinese population and implicate novel ASD risk genes and related pathway for further study.

PMID:: 28281572
PMCID:: PMC5345089
DOI:: 10.1038/srep44155

Free PMC Article

From HuGE Literature Finder Database

This database contains published literature on genetic associations and other human genome epidemiology

Genome-wide copy number variation analysis in a Chinese autism spectrum disorder cohort.
Scientific reports 2017 Mar 7 44155.
Guo Hui, Peng Yu, Hu Zhengmao, Li Ying, Xun Guanglei, Ou Jianjun, Sun Liangdan, Xiong Zhimin, Liu Yanling, Wang Tianyun, Chen Jingjing, Xia Lu, Bai Ting, Shen Yidong, Tian Qi, Hu Yiqiao, Shen Lu, Zhao Rongjuan, Zhang Xuejun, Zhang Fengyu, Zhao Jingping, Zou Xiaobing, Xia K
The association of CNTNAP2 rs7794745 gene polymorphism and autism in Iranian population.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 2017 Mar .
Zare Sahar, Mashayekhi Farhad, Bidabadi Elh
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
Nature neuroscience 2017 Mar .
C Yuen Ryan K, Merico Daniele, Bookman Matt, L Howe Jennifer, Thiruvahindrapuram Bhooma, Patel Rohan V, Whitney Joe, Deflaux Nicole, Bingham Jonathan, Wang Zhuozhi, Pellecchia Giovanna, Buchanan Janet A, Walker Susan, Marshall Christian R, Uddin Mohammed, Zarrei Mehdi, Deneault Eric, D'Abate Lia, Chan Ada J S, Koyanagi Stephanie, Paton Tara, Pereira Sergio L, Hoang Ny, Engchuan Worrawat, Higginbotham Edward J, Ho Karen, Lamoureux Sylvia, Li Weili, MacDonald Jeffrey R, Nalpathamkalam Thomas, Sung Wilson W L, Tsoi Fiona J, Wei John, Xu Lizhen, Tasse Anne-Marie, Kirby Emily, Van Etten William, Twigger Simon, Roberts Wendy, Drmic Irene, Jilderda Sanne, Modi Bonnie MacKinnon, Kellam Barbara, Szego Michael, Cytrynbaum Cheryl, Weksberg Rosanna, Zwaigenbaum Lonnie, Woodbury-Smith Marc, Brian Jessica, Senman Lili, Iaboni Alana, Doyle-Thomas Krissy, Thompson Ann, Chrysler Christina, Leef Jonathan, Savion-Lemieux Tal, Smith Isabel M, Liu Xudong, Nicolson Rob, Seifer Vicki, Fedele Angie, Cook Edwin H, Dager Stephen, Estes Annette, Gallagher Louise, Malow Beth A, Parr Jeremy R, Spence Sarah J, Vorstman Jacob, Frey Brendan J, Robinson James T, Strug Lisa J, Fernandez Bridget A, Elsabbagh Mayada, Carter Melissa T, Hallmayer Joachim, Knoppers Bartha M, Anagnostou Evdokia, Szatmari Peter, Ring Robert H, Glazer David, Pletcher Mathew T, Scherer Stephen
Ras-like without CAAX 2 (RIT2): a susceptibility gene for autism spectrum disorder.
Metabolic brain disease 2017 Feb .
Hamedani Shima Yazdandoost, Gharesouran Jalal, Noroozi Rezvan, Sayad Arezou, Omrani Mir Davood, Mir Atefeh, Afjeh Sarah Sadat Aghabozrg, Toghi Mehdi, Manoochehrabadi Saba, Ghafouri-Fard Soudeh, Taheri Mohamm
Refining the role of de novo protein-truncating variants in neurodevelopmental disorders by using population reference samples.
Nature genetics 2017 Feb .
Kosmicki Jack A, Samocha Kaitlin E, Howrigan Daniel P, Sanders Stephan J, Slowikowski Kamil, Lek Monkol, Karczewski Konrad J, Cutler David J, Devlin Bernie, Roeder Kathryn, Buxbaum Joseph D, Neale Benjamin M, MacArthur Daniel G, Wall Dennis P, Robinson Elise B, Daly Mark