Genomic Patterns of De Novo Mutation in Simplex Autism
In: Cell, Jg. 171 (2017-10-01), Heft 3
Online
academicJournal
- 710 - 722.e12
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 ∼1.5 × 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 × 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 × 10-3), suggesting a path forward for genetically characterizing more complex cases of autism.
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Genomic Patterns of De Novo Mutation in Simplex Autism
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Autor/in / Beteiligte Person: | Turner, Tychele N ; Coe, Bradley P ; Dickel, Diane E ; Hoekzema, Kendra ; Nelson, Bradley J ; Zody, Michael C ; Kronenberg, Zev N ; Hormozdiari, Fereydoun ; Raja, Archana ; Pennacchio, Len A ; Darnell, Robert B ; Eichler, Evan E |
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Zeitschrift: | Cell, Jg. 171 (2017-10-01), Heft 3 |
Veröffentlichung: | eScholarship, University of California, 2017 |
Medientyp: | academicJournal |
Umfang: | 710 - 722.e12 |
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