Letter/Communication
Functional impact of global rare copy number variation in autism spectrum disorders
Nature, Vol.466(7304), pp.368-372
07/15/2010
DOI: 10.1038/nature09146
PMID: 20531469
Abstract
The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
Details
- Title: Subtitle
- Functional impact of global rare copy number variation in autism spectrum disorders
- Creators
- Dalila Pinto - Program in Genetics and Genomic BiologyAlistair Pagnamenta - The Wellcome Trust Centre for Human Genetics [Oxford]Lambertus Klei - Department of Psychiatry [Pittsburgh]Richard Anney - Division of Mental Health and AddictionDaniele Merico - Banting and Best Department of Medical ResearchRegina Regan - Academic Centre on Rare DiseasesJudith Conroy - Academic Centre on Rare DiseasesTiago Magalhaes - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]Catarina Correia - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]Brett Abrahams - Department of NeurologyJoana Almeida - Unidade de Neurodesenvolvimento e AutismoElena Bacchelli - Department of Pharmacy and BiotechnologyGary Bader - Banting and Best Department of Medical ResearchAnthony Bailey - Department of PsychiatryGillian Baird - Newcomen CentreAgatino Battaglia - Department of Psychiatry and Behavioral Sciences [Stanford]Tom Berney - Child and Adolescent Mental HealthNadia Bolshakova - Division of Mental Health and AddictionSven Bölte - Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyPatrick Bolton - Department of Child and Adolescent PsychiatryThomas Bourgeron - Génétique Humaine et Fonctions CognitivesSean Brennan - Division of Mental Health and AddictionJessica Brian - Autism Research UnitSusan Bryson - Department of Pediatrics and PsychologyAndrew Carson - Program in Genetics and Genomic BiologyGuillermo Casallo - Program in Genetics and Genomic BiologyJillian Casey - Academic Centre on Rare DiseasesBrian Chung - Program in Genetics and Genomic BiologyLynne Cochrane - Division of Mental Health and AddictionChristina Corsello - Autism and Communicative Disorders CentreEmily Crawford - Department of Molecular Physiology & Biophysics and PsychiatryAndrew Crossett - Department of StatisticsCheryl Cytrynbaum - Program in Genetics and Genomic BiologyGeraldine Dawson - Scientific AffairsMaretha De Jonge - Department of PsychiatryRichard Delorme - Service de psychopathologie de l'enfant et de l'adolescentIrene Drmic - Autism Research UnitEftichia Duketis - Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyFrederico Duque - Unidade de Neurodesenvolvimento e AutismoAnnette Estes - Department of Speech and Hearing Sciences [Washington]Penny Farrar - The Wellcome Trust Centre for Human Genetics [Oxford]Bridget Fernandez - Disciplines of Genetics and MedicineSusan Folstein - John P. Hussman Institute for Human GenomicsEric Fombonne - Department of Psychiatry [Montréal]Christine Freitag - Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyJohn Gilbert - John P. Hussman Institute for Human GenomicsChristopher Gillberg - Department of Child and Adolescent PsychiatryJoseph Glessner - The Center for Applied GenomicsJeremy Goldberg - Department of Psychiatry and Behavioural NeurosciencesAndrew Green - University College DublinJonathan Green - Academic Department of Child PsychiatryStephen Guter - Department of PsychiatryHakon Hakonarson - The Center for Applied GenomicsElizabeth Heron - Division of Mental Health and AddictionMatthew Hill - Division of Mental Health and AddictionRichard Holt - The Wellcome Trust Centre for Human Genetics [Oxford]Jennifer Howe - Program in Genetics and Genomic BiologyGillian Hughes - Division of Mental Health and AddictionVanessa Hus - Autism and Communicative Disorders CentreRoberta Igliozzi - Department of Psychiatry and Behavioral Sciences [Stanford]Cecilia Kim - The Center for Applied GenomicsSabine Klauck - Division of Molecular Genome AnalysisAlexander Kolevzon - Human Genetics CenterOlena Korvatska - Department of MedicineVlad Kustanovich - Autism Genetic Resource ExchangeClara Lajonchere - Autism Genetic Resource ExchangeJanine Lamb - Centre for Integrated Genomic Medical Research, ManchesterMagdalena Laskawiec - Department of PsychiatryMarion Leboyer - Institut Mondor de Recherche BiomédicaleAnn Le Couteur - Child and Adolescent Mental HealthBennett Leventhal - Nathan Kline Institute for Psychiatric ResearchAnath Lionel - Program in Genetics and Genomic BiologyXiao-Qing Liu - Program in Genetics and Genomic BiologyCatherine Lord - Autism and Communicative Disorders CentreLinda Lotspeich - Department of Psychiatry and Behavioral Sciences [Stanford]Sabata Lund - Department of Molecular Physiology & Biophysics and PsychiatryElena Maestrini - Department of Pharmacy and BiotechnologyWilliam Mahoney - Department of PediatricsCarine Mantoulan - Centre d'Etudes et de Recherches en PsychoPathologieChristian Marshall - Program in Genetics and Genomic BiologyHelen Mcconachie - Child and Adolescent Mental HealthChristopher Mcdougle - Department of PsychiatryJane Mcgrath - Division of Mental Health and AddictionWilliam Mcmahon - Department of Developmental NeuroscienceAlison Merikangas - Division of Mental Health and AddictionOhsuke Migita - Program in Genetics and Genomic BiologyNancy Minshew - Departments of Psychiatry and NeurologyGhazala Mirza - The Wellcome Trust Centre for Human Genetics [Oxford]Jeff Munson - Department of Psychiatry and Behavioural SciencesStanley Nelson - Department of Human Genetics, Los AngelesCarolyn Noakes - Autism Research UnitAbdul Noor - Centre for Addiction and Mental HealthGudrun Nygren - Department of Child and Adolescent PsychiatryGuiomar Oliveira - Unidade de Neurodesenvolvimento e AutismoKaterina Papanikolaou - University Department of Child PsychiatryJeremy Parr - Institutes of Neuroscience and Health and SocietyBarbara Parrini - Department of Psychiatry and Behavioral Sciences [Stanford]Tara Paton - Program in Genetics and Genomic BiologyAndrew Pickles - Department of MedicineMarion Pilorge - Physiopathologie des Maladies du Système Nerveux Central
- Contributors
- Val C Sheffield (Contributor) - University of Iowa, Stead Family Department of Pediatrics
- Resource Type
- Letter/Communication
- Publication Details
- Nature, Vol.466(7304), pp.368-372
- DOI
- 10.1038/nature09146
- PMID
- 20531469
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4679
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 07/15/2010
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984070718202771
Metrics
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