Jon M. McClellan talks with
ScienceWatch.com and answers a few questions about
this month's Fast Breaking Paper in the field of
Neuroscience & Behavior.
Article Title: Rare structural variants disrupt
multiple genes in neurodevelopmental pathways in
Authors: Et Al.
Year: APR 25 2008
* Univ Washington, Dept Psychiat, Seattle, WA 98195
* Univ Washington, Dept Med, Seattle, WA 98195 USA.
* Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724
(addresses have been truncated)
Would you summarize the significance of your paper
in layman’s terms?
In this paper, we demonstrated that schizophrenia may be caused by many
different, individually rare severe mutations. My colleagues at the
University of Washington, and at Cold Spring Harbor Laboratory, used new
technologies to screen genome-wide for rare genomic deletions and
duplications that disrupt genes in individuals with schizophrenia, and in
healthy controls. Rare structural mutations were much more common in people
with schizophrenia. Most patients had a different mutation. The genes
altered by these mutations were disproportionately involved in
"...perhaps most individuals with
schizophrenia have a unique genetic
Our findings challenge the conventional belief that schizophrenia stems
from the collective action of shared common mutations, each one of which
may only have small to moderate effects on disease risk. The results of our
study suggest that many, perhaps most individuals with schizophrenia have a
unique genetic cause. If so, this has enormous implications for future
genetic research. Most current studies are designed to detect mutations
shared by a substantial proportion of people with the illness, and will
predictably fail if most patients have a different genetic cause.
Where do you see your research leading in the
This model also has important implications for treatment development.
Although most people with the illness may have a different genetic cause,
the genes disrupted by rare mutations may work in the same, or overlapping,
neurodevelopmental pathways. As they are identified, these pathways will
become the target for future treatment efforts.
Jon McClellan, M.D.
Department of Psychiatry and Behavioral Sciences
University of Washington
Seattle, Washington, USA