Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia.
Science
; 320(5875): 539-43, 2008 Apr 25.
Article
em En
| MEDLINE
| ID: mdl-18369103
ABSTRACT
Schizophrenia is a devastating neurodevelopmental disorder whose genetic influences remain elusive. We hypothesize that individually rare structural variants contribute to the illness. Microdeletions and microduplications >100 kilobases were identified by microarray comparative genomic hybridization of genomic DNA from 150 individuals with schizophrenia and 268 ancestry-matched controls. All variants were validated by high-resolution platforms. Novel deletions and duplications of genes were present in 5% of controls versus 15% of cases and 20% of young-onset cases, both highly significant differences. The association was independently replicated in patients with childhood-onset schizophrenia as compared with their parents. Mutations in cases disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways. These results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
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Encéfalo
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Deleção de Genes
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Duplicação Gênica
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Mutação
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Science
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos