Researchers at the Johns Hopkins University School of
Medicine and four other academic
medical centers have been awarded a $9.8 million grant from
the National Institute of Mental Health
to pin down inherited changes that occur outside a cell's
DNA sequence in people with schizophrenia.
Unlike changes or mutations in the DNA sequence itself,
epigenetic marks or alterations can be
affected by a lifetime of exposure to the environment in
which cells operate.
"A comprehensive understanding of a disease's
epigenome can provide hidden and valuable clues
to the role of diet, chemicals, infections and behaviors in
genetic predisposition to diseases," said
Andrew Feinberg, professor of medicine and director of Johns Hopkins' Center for Epigenetics in
its
Institute of Basic Biomedical Sciences, who is leading
the multi-institutional effort.
Because a significant indicator of epigenetic change
is our body chemistry's addition of so-
called methyl groups to DNA at specific sites, the research
will focus on identifying changes in
"methylated" sites in the epigenome that are associated
with schizophrenia.
The research team comprises scientists at Johns
Hopkins and the universities of Pennsylvania,
Alabama at Birmingham, Pittsburgh and California, San
Diego.
"Many researchers have identified genetic alterations
associated with schizophrenia, but so far
they do not account for a large proportion of schizophrenia
patients," Feinberg said. "Our work can
identify differences in methylation patterns seen in blood
samples or brain tissue samples from
patients with and without schizophrenia to fill out the
whole picture of both epigenetic and genetic
contributions to this disabling disorder."
The scientists will take advantage of DNA samples from
the National Institutes of Mental
Health genetics repository. They will analyze the
methylation patterns at nearly 10,000 sites
throughout the genomes of several thousand samples and
controls, choose the 50 most prominent sites
and map the locations of the methylation marks to identify
and analyze the activity of nearby genes.
"These studies will provide the first comprehensive
evaluation of the epigenetics of
schizophrenia and allow for unprecedented integration of
genetic and environmental information about
schizophrenia," Feinberg said.
Because epigenetic changes — unlike nuclear DNA
changes — are potentially reversible, "these
studies may also lead to exciting new avenues for
schizophrenia therapy," Feinberg noted.
Stephen Desiderio, director of the Institute for Basic
Biomedical Sciences at Johns Hopkins,
says the collaborative nature of the epigenome
investigation "promises to add quickly and richly to the
growing body of knowledge about schizophrenia."
The disorder affects an estimated 2 million adults in
the United States alone.
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