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Schizophrenia Bulletin 2003 29(1):169-178;
© 2003 by Oxford University Press and the Maryland Psychiatric Research Center (MPRC)
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© Oxford University Press

Monozygotic Twins Exhibit Numerous Epigenetic Differences: Clues to Twin Discordance?

Arturas Petronis, M.D., Ph.D., Irving I. Gottesman, Ph.D., Hon. F.R.C.Psych., Peixiang Kan, D.V.M., James L. Kennedy, M.D., F.R.C.P.C., Vincenzo S. Basile, M.Sc., Andrew D. Paterson, M.B., Ch.B., B.S. and Violeta Popendikyte, Ph.D.
Associate Professor; Centre for Addiction and Mental Health, and University of Toronto Toronto, Canada
Professor, Department of Psychiatry, and Senior Fellow, Department of Psychology, University of Minnesota Minneapolis, MN
Postdoctoral Fellow; Centre for Addiction and Mental Health, and University of Toronto Toronto, Canada
Professor, Centre for Addiction and Mental Health, and University of Toronto Toronto, Canada
medical student, McMaster University Hamilton, Canada
Assistant Professor, Department of Genetics and Genomic Biol ogy, Hospital for Sick Children Toronto
Research Scientist, Institute of Biotechnology Vilnius, Lithuania

Send reprint requests to Dr. A. Petronis, The Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 Canada; e-mail: arturas_petronis{at}camh.net

The goal of this pilot study was to explore the putative molecular mechanisms underlying the phenotypic discordance of monozygotic (MZ) twins. Thus, patterns of epigenetic DNA modification were investigated in the 5'-regulatory region of the dopamine D2 receptor gene (DRD2) in two pairs of monozygotic twins, one concordant and one discordant for schizophrenia. The bisulfite DNA modification-based approach was used to fine-map methylated cytosines in DRD2 in genomic DNA extracted from lymphocytes. Numerous DNA methylation differences were identified in the analyzed region both within and between the pairs of MZ twins. "Epigenetic distances" between MZ twins were calculated and used for the comparison of twin DRD2 methylation profiles. It was detected that the affected twin from the pair discordant for schizophrenia was epigenetically "closer" to the affected concordant twins than to his unaffected MZ co-twin. Although the epigenetic analysis was conducted for only several hundred base pairs of DRD2, the fact that numerous studies identified nonuniform methylation patterns across the clones of bisulfite-modified DNA from the same individual, as well as nonuniform patterns across different individuals, argues for the universality of intra- and interindividual epigenetic variation. Epigenetic studies should provide insight into the molecular causes of differential susceptibility to a disease in genetically identical organisms that may generalize to singletons.

Keywords: Monozygotic twins / discordance / schizophrenia / complex disease / epigenetics / DNA methylation / dopamine D2 receptor


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