title: Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia.
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.
authors.affiliation: Department of Psychological Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Dilihan
authors.initials: D
authors.lastname: Gumus
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Nadine
authors.initials: N
authors.lastname: Norton
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Georgieva
authors.forename: Murat
authors.initials: M
authors.lastname: Sari
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Fikret
authors.initials: F
authors.lastname: Erdogan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000235:genetics; D015820:Cadherins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D014644:Genetic Variation; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics*
chemical_list: C491636:APBA2 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C112162:neurexophilin