Novel Submicroscopic Chromosomal Abnormalities Detected in Autism Spectrum Disorder

Susan L. Christian, Camille W. Brune, Jyotsna Sudi, Ravinesh A. Kumar, Shaung Liu, Samer Karamohamed, Judith A. Badner, Seiichi Matsui, Jeffrey Conroy, Devin McQuaid, James Gergel, Eli Hatchwell, T. Conrad Gilliam, Elliot S. Gershon, Norma J. Nowak, William B. Dobyns, Edwin H. Cook

Research output: Contribution to journalArticlepeer-review

236 Scopus citations


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 ∼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.

Original languageEnglish (US)
Pages (from-to)1111-1117
Number of pages7
JournalBiological psychiatry
Issue number12
StatePublished - Jun 15 2008
Externally publishedYes

Bibliographical note

Funding Information:
We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. The Autism Genetic Resource Exchange is a program of Cure Autism Now and is supported, in part, by a grant to Daniel H. Geschwind (Principal Investigator) from the National Institute of Mental Health (MH64547).

Funding Information:
This work was partially funded by the National Alliance for Autism Research (SLC) and the National Institute of Neurological Diseases and Stroke (R01 NS51812) (SLC). This work was also supported by the National Institutes of Health/National Cancer Institute (P30 CA016056 ) (Roswell Park Cancer Institute's [RPCI] Cancer Center Support Grant).


  • Array comparative genomic hybridization
  • autism
  • microdeletions
  • microduplications


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