Helmholtz Gemeinschaft


Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia

Item Type:Article
Title:Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia
Creators Name:Kirov, G., Gumus, D., Chen, W., Norton, N., Georgieva, L., Sari, M., O'Donovan, M.C., Erdogan, F., Owen, M.J., Ropers, H.H. and Ullmann, R.
Abstract: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.
Keywords:Autistic Disorder, Cadherins, Carrier Proteins, Case-Control Studies, Pair 15 Human Chromosomes, Gene Dosage, Genetic Variation, Glycoproteins, Mental Retardation, Nerve Tissue Proteins, Neuropeptides, Nucleic Acid Hybridization, Schizophrenia
Source:Human Molecular Genetics
Publisher:Oxford University Press
Page Range:458-465
Date:1 February 2008
Official Publication:https://doi.org/10.1093/hmg/ddm323
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library