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Jewels That
May Help Explain Behavioral Disorders Found Among 'Junk' DNA
from the American College of Neuropsychopharmacology,
December 8, 2002
Original URL:
http://www.eurekalert.org/pub_releases/2002-12/acon-jtm120502.php
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Disorders:
Prader-Willi, Schizophrenia, Anorexia, Depression
Scientists have been looking for genes that can explain
behavioral disorders for 20 years without much success.
According to L. Alison McInnes of Mt. Sinai School of
Medicine, that may be because they have been concentrating
their efforts in the wrong places in the genome. Speaking on
Dec. 8 at the annual meeting of the American College of
Neuropsychopharmacology held in San Juan, Puerto Rico, McInnes
advised that those interested in genetic links to behavior
should start looking at places in the genome that produce
special molecules called small non-messenger RNA (smnRNA)
rather than concentrating on genes that code for proteins.
Current
genetic screening techniques do not pick up these sequences
because they are very small and not much is known about their
structure. So McInnes and her colleagues at Mt. Sinai have
created a computational and molecular screening technique
designed specifically to look for smnRNA molecules produced by
regions in the genome that have been associated with
behavioral disorders. Furthermore, they have used this method
to successfully identify such molecules in the first few genes
that they investigated, she reported.
The existence
of smnRNAs has been known for some time. Until recently, they
have been generally dismissed as unimportant. New studies are
finding that they are actually quite abundant and involved in
a wide variety of biological processes. As a result, some
scientists are beginning to speculate that they may represent
an entirely new class of gene and type of gene activity.
McInnes cited
the theoretical work of John Mattick and Michael Gagen at the
University of Queensland in Brisbane. Last year they published
a lengthy paper in Molecular Biology and Evolution in which
they argued that, rather than being useless, smnRNAs and
introns - the sequences in the genome between genes that code
for proteins that have been called junk DNA - form a powerful
network that can turn ordinary genes on and off at the proper
times.
"It appears
that smnRNA may be especially relevant for understanding
behavioral differences," McInnes said, "because they appear to
be particularly enriched in the brain. They represent a swift
and energy efficient means of regulating gene expression and
may be especially important for rapid regulatory events." Lack
of expression of an smnRNA has already been strongly
associated with one neuropsychiatric disorder, Prader Willi
syndrome, McInnes reported. Prader-Willi syndrome is
characterized by abnormally poor muscle tone and feeding
difficulties in early infancy, followed by excessive eating
and gradual development of morbid obesity. It is also
accompanied by cognitive impairment.
In the initial
trial of their new screen, the Mt. Sinai researchers
identified a possible smnRNA molecule produced by an intron of
the human corticotrophin-releasing hormone gene.
Corticotrophin releasing hormone (CRH) plays a key role in the
response of humans and other mammals to external threats. It
acts at a number of sites in the nervous system to control
automatic, behavioral and immunological responses of stress.
Alterations in
CRH neural activity appear to contribute to a number of mental
illnesses including depression, anxiety disorders and anorexia
nervosa. In addition, the CRH smnRNA appears to form a
complimentary match with a sequence in an untranslated region
associated with a receptor, called the NMDA-glutamate
receptor, which is widely implicated in schizophrenia and
other degenerative neurological disorders.
The members of
McInnes' research team are Esther Richler, Tara L. Lauriat,
Eric Mesh and Gary Benson from the biomathematics department.
Former team member Michael Inman also contributed to the
research. The team also acknowledges the valuable input of
Jerome Cavaille, a pioneer in the discovery of snmRNA
molecules. The project was supported by the Seaver Center for
Autism Research.
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