Chapter

Reelin Glycoprotein

pp 365-384

Epigenetic Modulation of Reelin Function in Schizophrenia and Bipolar Disorder

  • Hamid Mostafavi AbdolmalekyAffiliated withBiomedical Engineering Department, Boston UniversityLaboratory of Nutrition and Metabolism at BIDMC, Department of Surgery, Harvard Medical SchoolDepartments of Medicine (Genetics Program), Genetics & Genomics, and Pathology & Laboratory Medicine, Boston University School of MedicineDepartment of Psychiatry, Tehran Psychiatric Institute and Mental Health Research Center, Iran University of Medical Sciences
  • , Cassandra L. SmithAffiliated withBiomedical Engineering Department, Boston University
  • , Jin-Rong ZhouAffiliated withLaboratory of Nutrition and Metabolism at BIDMC, Department of Surgery, Harvard Medical School
  • , Sam ThiagalingamAffiliated withDepartments of Medicine (Genetics Program), Genetics & Genomics, and Pathology & Laboratory Medicine, Boston University School of Medicine

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Studies from several laboratories have provided convincing data to support the notion that altered DNA methylation in response to varying physiological and environmental conditions may play a critical role in the fine-tuning of gene expression. However, the establishment of abnormal gene promoter DNA methylation patterns resulting from environmental insults or dysfunctional genes of the DNA methylation machinery may destabilize the normal epigenetic modification of genes. This may affect the equilibrium in the differential gene expression patterns in the normal differentiated cells and tilt the balance toward the disease phenotype. The individuals with genetic susceptibility to specific diseases are likely to be more prone to abnormal DNA methylation. Thus, it is highly likely that the lack of a direct relationship between genotype and phenotype in major psychiatric disorders and the variability in the manifestation of diseases in individuals with identical genetic makeup could be derived from the changes in the DNA methylation patterns.