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Failure to Confirm CNVs as of Aetiological Significance in Twin Pairs Discordant for Schizophrenia

Published online by Cambridge University Press:  21 February 2012

Shinji Ono
Affiliation:
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Japan; Department of Neuropsychiatry, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Akira Imamura
Affiliation:
Department of Neuropsychiatry, Nagasaki University Graduate School of Biomedical Sciences, Japan. f1042@cc.nagasaki-u.ac.jp
Shinya Tasaki
Affiliation:
Department of Neuropsychiatry, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Naohiro Kurotaki
Affiliation:
Department of Neuropsychiatry, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Hiroki Ozawa
Affiliation:
Department of Neuropsychiatry, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Koh-ichiro Yoshiura
Affiliation:
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Yuji Okazaki
Affiliation:
Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
Corresponding
E-mail address:

Abstract

Copy number variations (CNVs) are common structural variations in the human genome that strongly affect genomic diversity and can play a role in the development of several diseases, including neurodevelopmental disorders. Recent reports indicate that monozygotic twins can show differential CNV profiles. We searched CNVs in monozygotic twins discordant for schizophrenia to identify susceptible loci for schizophrenia. Three pairs of monozygotic twins discordant for schizophrenia were subjected to analysis. Genomic DNA samples were extracted from peripheral blood lymphocytes. We adopted the Affymetrix Genome-Wide Human SNP (Single Nucleotide Polymorphism) Array 6.0 to detect copy number discordance using Partek Genomics Suite 6.5 beta. In three twin pairs, however, validations by quantitative PCR and DNA sequencing revealed that none of the regions had any discordance between the three twin pairs. Our results support the hypothesis that epigenetic changes or fluctuation in developmental process triggered by environmental factors mainly contribute to the pathogenesis of schizophrenia. Schizophrenia caused by strong genetics factors including copy number alteration or gene mutation may be a small subset of the clinical population.

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Copyright © Cambridge University Press 2010

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Failure to Confirm CNVs as of Aetiological Significance in Twin Pairs Discordant for Schizophrenia
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