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

Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, Gumus, Dilihan, Chen, Wei, Norton, Nadine ORCID: https://orcid.org/0000-0002-3848-4288, Georgieva, Lyudmila, Sari, Murat, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Erdogan, Fikret, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Ropers, Hans-Hilger and Ullmann, Reinhard 2008. Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Human Molecular Genetics 17 (3) , pp. 458-465. 10.1093/hmg/ddm323

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
ISSN:	0964-6906
Last Modified:	17 Oct 2022 08:37
URI:	https://orca.cardiff.ac.uk/id/eprint/623

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