title: Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder.
abstract: BACKGROUND
  One genetic mechanism known to be associated with autism spectrum disorders (ASD) is chromosomal abnormalities. The identification of copy number variants (CNV), i.e., microdeletions and microduplications that are undetectable at the level of traditional cytogenetic analysis, allows the potential association of submicroscopic chromosomal imbalances and human disease.
  
  
  METHODS
  We performed array comparative genomic hybridization (aCGH) utilizing a 19K whole genome tiling path bacterial artificial chromosome (BAC) microarray on 397 unrelated subjects with autism spectrum disorder. Common CNV were excluded using a control group comprised of 372 individuals from the National Institute of Mental Health (NIMH) Genetics Initiative Control samples. Confirmation studies were performed on all remaining CNV using fluorescence in situ hybridization (FISH), microsatellite analysis, and/or quantitative polymerase chain reaction (PCR) analysis.
  
  
  RESULTS
  A total of 51 CNV were confirmed in 46 ASD subjects. Three maternal interstitial duplications of 15q11-q13 known to be associated with ASD were identified. The other 48 CNV ranged in size from 189 kilobase (kb) to 5.5 megabase (Mb) and contained from 0 to approximately 40 National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) genes. Seven CNV were de novo and 44 were inherited.
  
  
  CONCLUSIONS
  Fifty-one autism-specific CNV were identified in 46 of 397 ASD patients using a 19K BAC microarray for an overall rate of 11.6%. These microdeletions and microduplications cause gene dosage imbalance in 272 genes, many of which could be considered as candidate genes for autism.
authors: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. schrist@bsd.uchicago.edu
authors: Susan L
authors: SL
authors: Christian
authors: Camille W
authors: CW
authors: Brune
authors: Jyotsna
authors: J
authors: Sudi
authors: Ravinesh A
authors: RA
authors: Kumar
authors: Shaung
authors: S
authors: Liu
authors: Samer
authors: S
authors: Karamohamed
authors: Judith A
authors: JA
authors: Badner
authors: Seiichi
authors: S
authors: Matsui
authors: Jeffrey
authors: J
authors: Conroy
authors: Devin
authors: D
authors: McQuaid
authors: James
authors: J
authors: Gergel
authors: Eli
authors: E
authors: Hatchwell
authors: T Conrad
authors: TC
authors: Gilliam
authors: Elliot S
authors: ES
authors: Gershon
authors: Norma J
authors: NJ
authors: Nowak
authors: William B
authors: WB
authors: Dobyns
authors: Edwin H
authors: EH
authors: Cook
mesh_terms: D000483:Alleles; D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics*; D044383:Black People / Q000235:genetics; D002648:Child; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D044465:White People / Q000235:genetics