EPIGENETIC STUDIES OF GENOMIC RETROELEMENTS IN MAJOR PSYCHOSIS

The

Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health

This work

is dedicated to the exploration of the role of epigenetic 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 (ERV’s),

Alu’s, and LINE’s, among others, which as a rule are

hypermethylated.  There is evidence from schizophrenia 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 illnesses

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 and genomic regions that exhibit evidence

for genetic linkage and association to major psychosis.  Genomic-wide epigenetic

study of the moiety of retroelements is now warranted, and I will discuss how