| Title: | Large mosaic copy number variations confer autism risk |
| Journal: | Nature Neuroscience |
| Published: | 11 Jan 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33432194/ |
| DOI: | https://doi.org/10.1038/s41593-020-00766-5 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854495 |
Publication 9536
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Abstract
Although germline de novo copy number variants (CNVs) are known causes of autism spectrum disorder (ASD), the contribution of mosaic (early-developmental) copy number variants (mCNVs) has not been explored. In this study, we assessed the contribution of mCNVs to ASD by ascertaining mCNVs in genotype array intensity data from 12,077 probands with ASD and 5,500 unaffected siblings. We detected 46 mCNVs in probands and 19 mCNVs in siblings, affecting 2.8-73.8% of cells. Probands carried a significant burden of large (>4-Mb) mCNVs, which were detected in 25 probands but only one sibling (odds ratio = 11.4, 95% confidence interval = 1.5-84.2, P = 7.4 × 10−4). Event size positively correlated with severity of ASD symptoms (P = 0.016). Surprisingly, we did not observe mosaic analogues of the short de novo CNVs recurrently observed in ASD (eg, 16p11.2). We further experimentally validated two mCNVs in postmortem brain tissue from 59 additional probands. These results indicate that mCNVs contribute a previously unexplained component of ASD risk.</p>
10 Authors
- Maxwell A. Sherman
- Rachel E. Rodin
- Giulio Genovese
- Caroline Dias
- Alison R. Barton
- Ronen E. Mukamel
- Bonnie Berger
- Peter J. Park
- Christopher A. Walsh
- Po-Ru Loh
1 Application
| Application ID | Title |
|---|---|
| 19808 | Exploring large-scale genetic mosaicism and its relationship to hematological malignancies |
Enabling scientific discoveries that improve human health