| Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. | |
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MedLine Citation:
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PMID: 21658581 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6-12.0, p = 2.4 × 10(-7)). We estimate there are 130-234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1. |
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Authors:
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Stephan J Sanders; A Gulhan Ercan-Sencicek; Vanessa Hus; Rui Luo; Michael T Murtha; Daniel Moreno-De-Luca; Su H Chu; Michael P Moreau; Abha R Gupta; Susanne A Thomson; Christopher E Mason; Kaya Bilguvar; Patricia B S Celestino-Soper; Murim Choi; Emily L Crawford; Lea Davis; Nicole R Davis Wright; Rahul M Dhodapkar; Michael DiCola; Nicholas M DiLullo; Thomas V Fernandez; Vikram Fielding-Singh; Daniel O Fishman; Stephanie Frahm; Rouben Garagaloyan; Gerald S Goh; Sindhuja Kammela; Lambertus Klei; Jennifer K Lowe; Sabata C Lund; Anna D McGrew; Kyle A Meyer; William J Moffat; John D Murdoch; Brian J O'Roak; Gordon T Ober; Rebecca S Pottenger; Melanie J Raubeson; Youeun Song; Qi Wang; Brian L Yaspan; Timothy W Yu; Ilana R Yurkiewicz; Arthur L Beaudet; Rita M Cantor; Martin Curland; Dorothy E Grice; Murat Günel; Richard P Lifton; Shrikant M Mane; Donna M Martin; Chad A Shaw; Michael Sheldon; Jay A Tischfield; Christopher A Walsh; Eric M Morrow; David H Ledbetter; Eric Fombonne; Catherine Lord; Christa Lese Martin; Andrew I Brooks; James S Sutcliffe; Edwin H Cook; Daniel Geschwind; Kathryn Roeder; Bernie Devlin; Matthew W State |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neuron Volume: 70 ISSN: 1097-4199 ISO Abbreviation: Neuron Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-10 Completed Date: 2011-08-23 Revised Date: 2012-04-06 |
Medline Journal Info:
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Nlm Unique ID: 8809320 Medline TA: Neuron Country: United States |
Other Details:
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Languages: eng Pagination: 863-85 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Program on Neurogenetics, Yale University School of Medicine, 230 South Frontage Road, New Haven, CT 06520, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Cadherins / genetics Cell Adhesion Molecules, Neuronal / genetics Child Child Development Disorders, Pervasive / genetics* Child, Preschool Chromosomes, Human, Pair 16 / genetics* Chromosomes, Human, Pair 7 / genetics* Chromosomes, Human, X / genetics DNA Copy Number Variations / genetics* Family Health* Female Gene Duplication / genetics Gene Expression Profiling Genome-Wide Association Study Genotype Humans Male Nerve Tissue Proteins / genetics Oligonucleotide Array Sequence Analysis Phenotype Proteins / genetics Siblings Ubiquitin Thiolesterase / genetics Williams Syndrome / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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K23 MH080954-05/MH/NIMH NIH HHS; R01 MH057881-15/MH/NIMH NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Cadherins; 0/Cell Adhesion Molecules, Neuronal; 0/FOR20 protein, human; 0/H-cadherin; 0/NRXN1 protein, human; 0/Nerve Tissue Proteins; 0/Proteins; EC 3.1.2.15/USP7 protein, human; EC 3.1.2.15/Ubiquitin Thiolesterase |
| Comments/Corrections | |
Comment In:
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Nat Rev Neurosci. 2011 Aug;12(8):429
[PMID:
21772319
]
Neuron. 2011 Jun 9;70(5):806-8 [PMID: 21658575 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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