The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Cell. 2022 Nov 10;185(23):4409-4427.e18. doi: 10.1016/j.cell.2022.10.009.
Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (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 parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants 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% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.
全面了解自闭症谱系障碍（ASD）的遗传学需要进行全基因组测序（WGS）。我们展示了自闭症之声 MSSNG 资源的最新版本，其中包括 5100 名 ASD 患者和 6212 名非 ASD 父母和兄弟姐妹（总计 n=11312）的 WGS 数据。在 MSSNG 和西蒙斯单倍型收集（SSC；n=9205）中研究了各种各样的遗传变异，我们在 MSSNG 中鉴定出 718/5100 名 ASD 患者（14.1%）和 SSC 中的 350/2419 名（14.5%）的 ASD 相关罕见变异。考虑到基因组结构，52%是核序列水平的变异，46%是核结构变异（包括拷贝数变异、倒位、大片段插入、单亲二体同质性和串联重复扩展），2%是线粒体变异。我们的研究为携带 ASD 相关罕见变异的家庭探索基因型-表型相关性提供了指南，并为扩展研究提供了切入点，以剖析在 ASD 患者中占 85%左右的仍为特发性的病因。
