Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia
| Autor: | Abhishek Bhandari, Ming K. Lee, Robert Long, Dheeraj Malhotra, Shane McCarthy, Andrew B. Singleton, Patricia Roccanova, Alexander Nord, Laila Noory, Jonathan Sebat, Zugen Chen, Sarah B. Pierce, Stanley F. Nelson, Mary Kusenda, Sunday M. Stray, Peter Gochman, Vlad Makarov, Tom Walsh, Caitlin Rippey, Evan E. Eichler, Judith L. Rapoport, Robert L. Findling, Linmarie Sikich, Anjené M. Addington, Barry Merriman, Thomas Stromberg, B. Lakshmi, Sean Davis, Carl Baker, Paul S. Meltzer, Greg M. Cooper, Jon McClellan, Mary Claire King, Philip Butler, Kristen L. Eckstrand, Nitin Gogtay |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Psychosis Receptor ErbB-4 Adolescent Molecular Sequence Data Biology Bioinformatics medicine.disease_cause Polymorphism Single Nucleotide Neurodevelopmental disorder Gene Duplication Gene duplication medicine Humans Genetic Predisposition to Disease Amino Acid Sequence Age of Onset Child Gene Oligonucleotide Array Sequence Analysis Genetics Neurons Mutation Multidisciplinary Genome Human Brain medicine.disease ErbB Receptors Excitatory Amino Acid Transporter 1 Schizophrenia Case-Control Studies Human genome Female Gene Deletion Comparative genomic hybridization Signal Transduction |
| Zdroj: | Science (New York, N.Y.). 320(5875) |
| ISSN: | 1095-9203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|