Background
Clinical studies have identified several regions of the genome with copy number variations
(CNVs) associated with diverse neurodevelopmental behavioral disorders.
Methods
We analyzed 1 million (M) single nucleotide polymorphism genotype arrays for evidence
of previously reported recurrent CNVs and enriched genome-wide CNV burden in DNA from
600 brains, including 441 individuals with various psychiatric diagnoses. We explored
gene expression in the dorsolateral prefrontal cortex in selected cases with CNVs
and in other subjects with Illumina BeadArrays (568 subjects in total) and additionally
in 66–92 subjects with quantitative real-time polymerase chain reaction.
Results
The CNVs in previously reported genomic regions were identified in 4 of 193 patients
with the diagnosis of schizophrenia (1q21.1, 11q25, 15q11.2, 22q11), 4 of 238 patients
with mood disorders (11q25, 15q11.2, 22q11), and 1 of 10 patients with autism (2p16.3).
No evidence of increased genome-wide CNV burden was observed in cases with schizophrenia
or mood disorders, although the study is underpowered to observe rare events. Messenger
RNA expression patterns suggested incomplete molecular penetrance of observed CNVs.
Conclusions
Our data confirm in brain DNA the presence of certain recurrent CNVs in a small percentage
of patients with psychiatric diagnoses.
Key Words
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Article info
Publication history
Published online: July 16, 2012
Accepted:
June 12,
2012
Received in revised form:
June 11,
2012
Received:
November 18,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Brain Copy Number Variants and Neuropsychiatric TraitsBiological PsychiatryVol. 72Issue 8
- PreviewIn this issue of Biological Psychiatry, genomic analysis of patients with neuropsychiatric disease reveals the presence of rare copy number variants (CNVs) in about 2% of the approximately 400 brains examined (1). CNVs represent deviations from the normal diploid state (n = 2) at a given position or locus in the human genome because of a deletion or duplication at that locus. The CNVs identified have been associated previously with psychiatric illness in large-scale, case-control studies that utilized genomic DNA isolated from blood lymphocytes; however, such CNV have not been directly observed in brains of individuals with neuropsychiatric illness.
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