Clinical studies have identified several regions of the genome with copy number variations (CNVs) associated with diverse neurodevelopmental behavioral disorders.
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.
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.
Our data confirm in brain DNA the presence of certain recurrent CNVs in a small percentage of patients with psychiatric diagnoses.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Biological Psychiatry
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia.Science. 2008; 320: 539-543
- Rare chromosomal deletions and duplications increase risk of schizophrenia.Nature. 2008; 455: 237-241
- Large recurrent microdeletions associated with schizophrenia.Nature. 2008; 455: 232-236
- Strong association of de novo copy number mutations with sporadic schizophrenia.Nat Genet. 2008; 40: 880-885
- Accurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function.PLoS Genet. 2010; 6: e1001097
- Copy number variants in schizophrenia: Confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications.Am J Psychiatry. 2011; 168: 302-316
- Rare de novo variants associated with autism implicate a large functional network of genes.Neuron. 2011; 70: 898-907
- Ontogenetic de novo copy number variations (CNVs) as a source of genetic individuality: Studies on two families with MZD twins for schizophrenia.PLoS One. 2011; 6: e17125
- Critical factors in gene expression in postmortem human brain: Focus on studies in schizophrenia.Biol Psychiatry. 2006; 60: 650-658
- PennCNV: An integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data.Genome Res. 2007; 17: 1665-1674
- QuantiSNP: An Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data.Nucleic Acids Res. 2007; 35: 2013-2025
- Lumi: A pipeline for processing Illumina microarray.Bioinformatics. 2008; 24: 1547-1548
- Adjusting batch effects in microarray expression data using Empirical Bayes methods.Biostatistics. 2007; 8: 118-127
- Capturing heterogeneity in gene expression studies by surrogate variable analysis.PLoS Genet. 2007; 3: 1724-1735
- Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: A susceptibility region for neurological dysfunction including developmental and language delay.Hum Genet. 2011; 130: 517-528
- Mapping autism risk loci using genetic linkage and chromosomal rearrangements.Nat Genet. 2007; 39: 319-328
- Temporal dynamics and genetic control of the human neocortical transcriptome across the lifespan.Nature. 2011; 478: 519-524
Published online: July 16, 2012
Accepted: June 12, 2012
Received in revised form: June 11, 2012
Received: November 18, 2011
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
ScienceDirectAccess this article on ScienceDirect
- 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.