Cited by 377Genomic variations and chromosomal abnormalitiesSchizophrenia research and treatmentGenetics and Neurodevelopmental Disorders

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

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Kirov, G., Gumus, D., Chen, W., Norton, N., Georgieva, L., Sari, M., O'Donovan, M. C, Erdogan, F. +3 more·2007·Human Molecular Genetics

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.

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Authors
Kirov, G., Gumus, D., Chen, W., Norton, N., Georgieva, L., Sari, M., O'Donovan, M. C., Erdogan, F., Owen, M. J., Ropers, H.-H., & Ullmann, R.
Affiliations
  • Cardiff University (GB)
  • Max Planck Society (DE)
Venue
Human Molecular Genetics
Published
2007-10-03
Volume
17
Issue
3
Pages
458-465
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
OpenAlex
W2108284636
Cited by
377
References
56
Citations by year
2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 11 · 2019: 13 · 2018: 7 · 2017: 11 · 2016: 14 · 2015: 24 · 2014: 25 · 2013: 30 · 2012: 35
FWCI
23.94
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Wellcome Trust
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
schizophrenia, copy number variation, NRXN1, de novo duplication, synaptic development, neurodevelopmental disorders, genetic interactions
MeSH terms
Adolescent, Adult, Autistic Disorder, Carrier Proteins, Chromosomes, Human, Pair 15, Female, Glycoproteins, Humans, Male, Intellectual Disability, Middle Aged, Nerve Tissue Proteins, Neuropeptides, Nucleic Acid Hybridization, Schizophrenia, Genetic Variation, Cadherins, Case-Control Studies, Gene Dosage

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