Human Molecular Genetics Advance Access originally published online on November 6, 2007
Human Molecular Genetics 2008 17(3):458-465; doi:10.1093/hmg/ddm323
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Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia
1 Department of Psychological Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK 2 Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195 Berlin, Germany
* To whom correspondence should be addressed. Tel: +44 2920743058; Fax: +44 2920746554; Email: owenmj{at}cardiff.ac.uk
Received September 21, 2007; Revised October 29, 2007; Accepted November 5, 2007
Copy number variations (CNVs) account for a substantial proportion of human genomic variation, and have been shown to cause neurodevelopmental disorders. We sought to determine the relevance of CNVs to the aetiology of schizophrenia (SZ). Whole-genome, high-resolution, tiling path BAC array comparative genomic hybridization (array CGH) was employed to test DNA from 93 individuals with DSM-IV SZ. Common DNA copy number changes that are unlikely to be directly pathogenic in SZ were filtered out by comparison to a reference dataset of 372 control individuals analyzed in our laboratory, and a screen against the Database of Genomic Variants. The remaining aberrations were validated with Affymetrix 250K SNP arrays or 244K Agilent oligo-arrays and tested for inheritance from the parents. A total of 13 aberrations satisfied our criteria. Two of them are very likely to be pathogenic. The first one is a deletion at 2p16.3 that was present in an affected sibling and disrupts NRXN1. The second one is a de novo duplication at 15q13.1 spanning APBA2. The proteins of these two genes interact directly and play a role in synaptic development and function. Both genes have been affected by CNVs in patients with autism and mental retardation, but neither has been previously implicated in SZ.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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