加拿大病童医院Morgan Quirbach团队通过全面的全基因组序列注释揭示自闭症的基因组结构。这一研究成果发表在2022年11月10日出版的国际学术期刊《细胞》上。
研究人员报道了自闭症之声MSSNG资源的最新版本，其中包括来自5100名闭症谱系障碍（ASD）患者和6212名非ASD父母和兄弟姐妹的全基因组测序（WGS）数据（总人数=11312人）。通过检查MSSNG和Simons Simplex Collection（SSC；n=9,205）中的各种遗传变异，研究人员在MSSNG的718/5100名ASD患者（14.1%）和SSC的350/2419名患者（14.5%）中确定了ASD相关的罕见变异。考虑到基因组结构，52%是核序列级变异，46%是核结构变异（包括拷贝数变异、倒置、大面积插入、单亲二倍体和串联重复扩增），2%是线粒体变异。
这项研究为探索携带ASD相关罕见变体家庭的基因型与表型的相关性提供了指南，并作为一个切入点，对85%以上仍为特发性ASD人群的病因进行了必要的扩大研究。
据悉，充分了解ASD的遗传学需要WGS。
附：英文原文
Title: Genomic architecture of autism from comprehensive whole-genome sequence annotation
Author: Brett Trost, Bhooma Thiruvahindrapuram, Ada J.S. Chan, Worrawat Engchuan, Edward J. Higginbotham, Jennifer L. Howe, Livia O. Loureiro, Miriam S. Reuter, Delnaz Roshandel, Joe Whitney, Mehdi Zarrei, Matthew Bookman, Cherith Somerville, Rulan Shaath, Mona Abdi, Elbay Aliyev, Rohan V. Patel, Thomas Nalpathamkalam, Giovanna Pellecchia, Omar Hamdan, Gaganjot Kaur, Zhuozhi Wang, Jeffrey R. MacDonald, John Wei, Wilson W.L. Sung, Sylvia Lamoureux, Ny Hoang, Thanuja Selvanayagam, Nicole Deflaux, Melissa Geng, Siavash Ghaffari, John Bates, Edwin J. Young, Qiliang Ding, Carole Shum, Lia DAbate, Clarrisa A. Bradley, Annabel Rutherford, Vernie Aguda, Beverly Apresto, Nan Chen, Sachin Desai, Xiaoyan Du, Matthew L.Y. Fong, Sanjeev Pullenayegum, Kozue Samler, Ting Wang, Karen Ho, Tara Paton, Sergio L. Pereira, Jo-Anne Herbrick, Richard F. Wintle, Jonathan Fuerth, Juti Noppornpitak, Heather Ward, Patrick Magee, Ayman Al Baz, Usanthan Kajendirarajah, Sharvari Kapadia, Jim Vlasblom, Monica Valluri, Joseph Green, Vicki Seifer, Morgan Quirbach
Issue&Volume: 2022/11/10
Abstract: Fully understanding autism spectrum disorder (ASD) genetics requires whole-genomesequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource,which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parentsand siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNGand the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rarevariants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC(14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants,46% were nuclear structural variants (including copy-number variants, inversions,large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% weremitochondrial variants. Our study provides a guidebook for exploring genotype-phenotypecorrelations in families who carry ASD-associated rare variants and serves as an entrypoint to the expanded studies required to dissect the etiology in the ～85% of theASD population that remain idiopathic.
DOI: 10.1016/j.cell.2022.10.009
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01324-1