Journal article
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
Nature (London), Vol.459(7246), pp.569-573
05/28/2009
DOI: 10.1038/nature07953
PMCID: PMC2925224
PMID: 19404257
Abstract
Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies focusing on candidate genes or genomic regions have identified several copy number variations (CNVs) that are associated with an increased risk of ASDs. Here we present the results from a whole-genome CNV study on a cohort of 859 ASD cases and 1,409 healthy children of European ancestry who were genotyped with ∼550,000 single nucleotide polymorphism markers, in an attempt to comprehensively identify CNVs conferring susceptibility to ASDs. Positive findings were evaluated in an independent cohort of 1,336 ASD cases and 1,110 controls of European ancestry. Besides previously reported ASD candidate genes, such as NRXN1 (ref. 10) and CNTN4 (refs 11, 12), several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls (P = 9.5 × 10-3). Furthermore, CNVs within or surrounding genes involved in the ubiquitin pathways, including UBE3A, PARK2, RFWD2 and FBXO40, were affected by CNVs not observed in controls (P = 3.3 × 10-3). We also identified duplications 55 kilobases upstream of complementary DNA AK123120 (P = 3.6 × 10-6). Although these variants may be individually rare, they target genes involved in neuronal cell-adhesion or ubiquitin degradation, indicating that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.
Details
- Title: Subtitle
- Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
- Creators
- Nancy J Minshew - Departments of Psychiatry and Neurology, University of Pittsburg School of MedicineKelly Thomas - Center for Applied Genomics, Children's Hospital of PhiladelphiaJohn I Nurnberger - Indiana UniversityEmily L Crawford - Center for Molecular Neuroscience and Vanderbilt Kennedy Center, Vanderbilt UniversityFrederick Otieno - Center for Applied Genomics, Children's Hospital of PhiladelphiaGeraldine Dawson - University of WashingtonDavid J Posey - Indiana UniversityKiran Annaiah - Center for Applied Genomics, Children's Hospital of PhiladelphiaWendy Glaberson - Center for Applied Genomics, Children's Hospital of PhiladelphiaShawn Wood - Departments of Psychiatry and Human Genetics, University of PittsburghKacie J Meyer - University of IowaPatrick M. A Sleiman - Center for Applied Genomics, Children's Hospital of PhiladelphiaJudith Miller - University of UtahJeffrey Munson - University of WashingtonCecilia E Kim - Center for Applied Genomics, Children's Hospital of PhiladelphiaJonathan P Bradfield - Center for Applied Genomics, Children's Hospital of PhiladelphiaLatha Soorya - Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of MedicineEdward C Frackelton - Center for Applied Genomics, Children's Hospital of PhiladelphiaMaja Bucan - Dept of Genetics, Biology and Biostatistics, University of Pennsylvania School of MedicineTakeshi Sakurai - Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of MedicineEvdokia Anagnostou - Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of MedicineCuiping Hou - Center for Applied Genomics, Children's Hospital of PhiladelphiaJoseph Piven - Neurodevelopmental Disorders Research Center and Department of Psychiatry, University of North CarolinaRobert T Schultz - Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of MedicineHaitao Zhang - Center for Applied Genomics, Children's Hospital of PhiladelphiaEdwin H Cook - Institute for Juvenile Research and Department of Psychiatry, University of Illinois at ChicagoGerard D Schellenberg - Department of Pathology and Laboratory Medicine, University of Pennsylvania School of MedicineKai Wang - Center for Applied Genomics, Children's Hospital of PhiladelphiaJames Flory - Center for Applied Genomics, Children's Hospital of PhiladelphiaDanielle S Rudd - University of IowaJohn A Sweeney - Institute for Juvenile Research and Department of Psychiatry, University of Illinois at ChicagoDanielle Zurawiecki - Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of MedicineStruan F. A Grant - Center for Applied Genomics, Children's Hospital of Philadelphia Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of MedicineShana Michaels - Departments of Psychiatry and Human Genetics, University of PittsburghSusan E Levy - Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of MedicineRosetta Chiavacci - Center for Applied Genomics, Children's Hospital of PhiladelphiaWilliam M McMahon - University of UtahCamille W Brune - Institute for Juvenile Research and Department of Psychiatry, University of Illinois at ChicagoOlena Korvatska - University of WashingtonGuiqing Cai - Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of MedicineChristopher J McDougle - Indiana UniversityLambertus Klei - Departments of Psychiatry and Human Genetics, University of PittsburghHakon Hakonarson - Center for Applied Genomics, Children's Hospital of Philadelphia Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of MedicineAlexander Kolevzon - Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of MedicineMaria Garris - Center for Applied Genomics, Children's Hospital of PhiladelphiaJeremy M Silverman - Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of MedicineThomas H Wassink - University of IowaThomas Owley - Institute for Juvenile Research and Department of Psychiatry, University of Illinois at ChicagoJoseph T Glessner - Center for Applied Genomics, Children's Hospital of PhiladelphiaJames S Sutcliffe - Center for Molecular Neuroscience and Vanderbilt Kennedy Center, Vanderbilt UniversityJennifer Reichert - Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of MedicineLea K Davis - University of IowaRaphael Bernier - University of WashingtonRachel M Game - Center for Molecular Neuroscience and Vanderbilt Kennedy Center, Vanderbilt UniversityBernie Devlin - Departments of Psychiatry and Human Genetics, University of PittsburghHilary Coon - University of UtahMarcin Imielinski - Center for Applied Genomics, Children's Hospital of PhiladelphiaAnnette Estes - University of WashingtonJoseph D Buxbaum - Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of Medicine Departments of Neuroscience, and Genetics and Genomic Sciences, Mount Sinai School of Medicine
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.459(7246), pp.569-573
- DOI
- 10.1038/nature07953
- PMID
- 19404257
- PMCID
- PMC2925224
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 05/28/2009
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics
- Record Identifier
- 9984003901702771
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