PMID- 18374305 OWN - NLM STAT- MEDLINE DCOM- 20080815 LR - 20231105 IS - 1873-2402 (Electronic) IS - 0006-3223 (Print) IS - 0006-3223 (Linking) VI - 63 IP - 12 DP - 2008 Jun 15 TI - Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. PG - 1111-7 LID - 10.1016/j.biopsych.2008.01.009 [doi] AB - 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. FAU - Christian, Susan L AU - Christian SL AD - Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. schrist@bsd.uchicago.edu FAU - Brune, Camille W AU - Brune CW FAU - Sudi, Jyotsna AU - Sudi J FAU - Kumar, Ravinesh A AU - Kumar RA FAU - Liu, Shaung AU - Liu S FAU - Karamohamed, Samer AU - Karamohamed S FAU - Badner, Judith A AU - Badner JA FAU - Matsui, Seiichi AU - Matsui S FAU - Conroy, Jeffrey AU - Conroy J FAU - McQuaid, Devin AU - McQuaid D FAU - Gergel, James AU - Gergel J FAU - Hatchwell, Eli AU - Hatchwell E FAU - Gilliam, T Conrad AU - Gilliam TC FAU - Gershon, Elliot S AU - Gershon ES FAU - Nowak, Norma J AU - Nowak NJ FAU - Dobyns, William B AU - Dobyns WB FAU - Cook, Edwin H Jr AU - Cook EH Jr LA - eng GR - P30 CA016056/CA/NCI NIH HHS/United States GR - R01 NS051812-01/NS/NINDS NIH HHS/United States GR - R01 NS051812/NS/NINDS NIH HHS/United States GR - WT_/Wellcome Trust/United Kingdom GR - R01 MH064547/MH/NIMH NIH HHS/United States GR - R01 NS51812/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080328 PL - United States TA - Biol Psychiatry JT - Biological psychiatry JID - 0213264 SB - IM MH - Alleles MH - Autistic Disorder/diagnosis/*genetics MH - Black People/genetics MH - Child MH - *Chromosome Aberrations MH - Chromosome Deletion MH - Chromosomes, Artificial, Bacterial/genetics MH - Chromosomes, Human, Pair 15/genetics MH - DNA Mutational Analysis MH - Female MH - Gene Dosage/*genetics MH - Gene Duplication MH - Genetic Predisposition to Disease/genetics MH - Genetic Variation/*genetics MH - Genotype MH - Humans MH - Male MH - Nucleic Acid Hybridization/genetics MH - Oligonucleotide Array Sequence Analysis MH - Phenotype MH - Polymerase Chain Reaction MH - White People/genetics PMC - PMC2440346 MID - NIHMS53749 COIS- Financial disclosures and conflicts of interest Susan L. Christian reported no biomedical interests or potential conflicts of interest. Camille W. Brune reported no biomedical interests or potential conflicts of interest. Jyotsna Sudi reported no biomedical interests or potential conflicts of interest. Ravinesh A. Kumar reported no biomedical interests or potential conflicts of interest. Shaung Liu reported no biomedical interests or potential conflicts of interest. Samer KaraMohamed reported no biomedical interests or potential conflicts of interest. Judith A. Badner reported no biomedical interests or potential conflicts of interest. Seiichi Matsui reported no biomedical interests or potential conflicts of interest. Jeffrey Conroy reported no biomedical interests or potential conflicts of interest. Devin McQuaid reported no biomedical interests or potential conflicts of interest. James Gergel reported no biomedical interests or potential conflicts of interest. Eli Hatchwell reported no biomedical interests or potential conflicts of interest. T. Conrad Gilliam reported no biomedical interests or potential conflicts of interest. Elliot S. Gershon reports that he is a consultant to Epix Pharmaceuticals, which has no interest in these findings. Norma J. Nowak reported no biomedical interests or potential conflicts of interest. William B. Dobyns reported no biomedical interests or potential conflicts of interest. Edwin H. Cook, Jr reported no biomedical interests or potential conflicts of interest. EDAT- 2008/04/01 09:00 MHDA- 2008/08/16 09:00 PMCR- 2008/06/26 CRDT- 2008/04/01 09:00 PHST- 2007/12/05 00:00 [received] PHST- 2008/01/10 00:00 [revised] PHST- 2008/01/22 00:00 [accepted] PHST- 2008/04/01 09:00 [pubmed] PHST- 2008/08/16 09:00 [medline] PHST- 2008/04/01 09:00 [entrez] PHST- 2008/06/26 00:00 [pmc-release] AID - S0006-3223(08)00103-0 [pii] AID - 10.1016/j.biopsych.2008.01.009 [doi] PST - ppublish SO - Biol Psychiatry. 2008 Jun 15;63(12):1111-7. doi: 10.1016/j.biopsych.2008.01.009. Epub 2008 Mar 28.