title: Strong association of de novo copy number mutations with autism.
abstract: We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic regions were validated by higher-resolution CGH, paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (3%) of patients with an affected first-degree relative, and in 2 out of 196 (1%) of controls. Most de novo CNVs were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. sebat@cshl.edu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sebat
authors.forename: B
authors.initials: B
authors.lastname: Lakshmi
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Malhotra
authors.forename: Jennifer
authors.initials: J
authors.lastname: Troge
authors.forename: Christa
authors.initials: C
authors.lastname: Lese-Martin
authors.forename: Tom
authors.initials: T
authors.lastname: Walsh
authors.forename: Boris
authors.initials: B
authors.lastname: Yamrom
authors.forename: Seungtai
authors.initials: S
authors.lastname: Yoon
authors.forename: Alex
authors.initials: A
authors.lastname: Krasnitz
authors.forename: Jude
authors.initials: J
authors.lastname: Kendall
authors.forename: Anthony
authors.initials: A
authors.lastname: Leotta
authors.forename: Deepa
authors.initials: D
authors.lastname: Pai
authors.forename: Ray
authors.initials: R
authors.lastname: Zhang
authors.forename: Yoon-Ha
authors.initials: YH
authors.lastname: Lee
authors.forename: James
authors.initials: J
authors.lastname: Hicks
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Spence
authors.forename: Annette T
authors.initials: AT
authors.lastname: Lee
authors.forename: Kaija
authors.initials: K
authors.lastname: Puura
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: David
authors.initials: D
authors.lastname: Ledbetter
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Joel
authors.initials: J
authors.lastname: Bregman
authors.forename: James S
authors.initials: JS
authors.lastname: Sutcliffe
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Jobanputra
authors.forename: Wendy
authors.initials: W
authors.lastname: Chung
authors.forename: Dorothy
authors.initials: D
authors.lastname: Warburton
authors.forename: Mary-Claire
authors.initials: MC
authors.lastname: King
authors.forename: David
authors.initials: D
authors.lastname: Skuse
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: T Conrad
authors.initials: TC
authors.lastname: Gilliam
authors.forename: Kenny
authors.initials: K
authors.lastname: Ye
authors.forename: Michael
authors.initials: M
authors.lastname: Wigler
mesh_terms: D020817:Asperger Syndrome / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D020732:Cytogenetic Analysis; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D018095:Germ-Line Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008390:Markov Chains; D018895:Microsatellite Repeats; D009154:Mutation; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010290:Parents; D035781:Siblings