Analysis of copy number variations in brain DNA from patients with schizophrenia and other psychiatric disorders.
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.
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD 21205, USA.
Tianzhang
T
Ye
Barbara K
BK
Lipska
Ran
R
Tao
Thomas M
TM
Hyde
Liqin
L
Wang
Chao
C
Li
Kwang H
KH
Choi
Richard E
RE
Straub
Joel E
JE
Kleinman
Daniel R
DR
Weinberger
D001321:Autistic Disorder / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D019964:Mood Disorders / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*