期刊
CELL
卷 171, 期 3, 页码 710-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2017.08.047
关键词
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资金
- Simons Foundation Autism Research Initiative [SFARI 303241, 385035]
- NIH [R01MH101221, UM1 HG008901, R01HG003988, U54HG006997]
- National Human Genome Research Institute
- National Heart, Lung, and Blood Institute
- GSP Coordinating Center [U24HG008956]
- Department of Energy, University of California [DE-AC02-05CH11231]
- Autism Science Foundation [16-008]
To further our understanding of the genetic etiology of autism, we generated and analyzed genome sequence data from 516 idiopathic autism families (2,064 individuals). This resource includes > 59 million single-nucleotide variants (SNVs) and 9,212 private copy number variants (CNVs), of which 133,992 and 88 are de novo mutations (DNMs), respectively. We estimate a mutation rate of similar to 1.5 x 10(-8) SNVs per site per generation with a significantly higher mutation rate in repetitive DNA. Comparing probands and unaffected siblings, we observe several DNM trends. Probands carry more gene-disruptive CNVs and SNVs, resulting in severe missense mutations and mapping to predicted fetal brain promoters and embryonic stem cell enhancers. These differences become more pronounced for autism genes (p = 1.8 x 10(-3), OR = 2.2). Patients are more likely to carry multiple coding and noncoding DNMs in different genes, which are enriched for expression in striatal neurons (p = 3 x 10(-3)), suggesting a path forward for genetically characterizing more complex cases of autism.
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