Epigenetic studies of genomic retroelements in major psychosis

Kan, Pei-Xiang; Popendikyte, Violeta; Kaminsky, Zachary A.; Yolken, Robert H.; Petronis, Arturas

doi:10.1016/j.schres.2003.09.004

« Previous Next »Schizophrenia Research
Volume 67, Issue 1 , Pages 95-106, 1 March 2004

Epigenetic studies of genomic retroelements in major psychosis

Pei-Xiang Kan
- The Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, University of Toronto, Room 28, 250 College Street, Toronto, Ontario, Canada M5T 1R8
Violeta Popendikyte
- The Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, University of Toronto, Room 28, 250 College Street, Toronto, Ontario, Canada M5T 1R8
- Institute of Biotechnology, Graiciuno 8, Vilnius 2028, Lithuania
Zachary A. Kaminsky
- The Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, University of Toronto, Room 28, 250 College Street, Toronto, Ontario, Canada M5T 1R8
Robert H. Yolken
- Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4933, USA
Arturas Petronis
- Corresponding author. Tel.: +1-416-535-8501x4880; fax: +1-416-979-4666.
- The Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, University of Toronto, Room 28, 250 College Street, Toronto, Ontario, Canada M5T 1R8

Received 15 April 2003; received in revised form 10 September 2003; accepted 12 September 2003.

Abstract

This work is dedicated to the exploration of the role of epigenetic (epiG) factors in major psychosis. One of the key functions of epigenetic modification of the genome of eukaryotic cells is to suppress transcriptional activity of the retroelements. Examples of retroelements are endogenous retroviral sequences (ERVs), Alu's, and LINEs, among others, which as a rule are hypermethylated. There is evidence from schizophrenia (SCH) and other human complex diseases that some of the genomic retroelements become transcribed in the affected tissues. Our goal was to screen DNA samples from post-mortem brain tissues of individuals who were affected with major psychiatric illness for retroelements that were located in the hypomethylated fraction of the genomic DNA. Over 100 Alu sequences were cloned, sequenced, and mapped to the human genome. A substantial portion of the cloned Alu's are located close to or within the genes that may be interesting targets for further genetic, transcription, and epigenetic studies.

Keywords: Epigenetics, DNA methylation, Schizophrenia, Bipolar disorder, Retroelements, Alu sequences, Endogenous retroviruses, Post-mortem brain