Why Some People Get Sick... and Others Get Sicker
A gene that turns a chronic inherited neurological disorder — which produces
tremor and muscle weakness in laboratory mice — into a lethal disease that
paralyzes and kills them within a few weeks of birth, has been discovered by
U-M scientists. Called Scnm1, the gene is one of a small group of recently
discovered "modifier" genes that interact with other genes to alter the physical
effects of inherited diseases.
Michelle Trudeau, Miriam Meisler and David Buchner Photo:
Marcia Ledford |
There are many inherited diseases — including cystic fibrosis, amyotrophic
lateral sclerosis (ALS) and epilepsy — where symptoms vary widely, even between
members of the same family. Understanding how modifier genes work could help
scientists solve a fundamental mystery of genetics: Why do people with identical
genetic mutations often differ in the severity or age of onset of the same
inherited disease?
"In our study with mice, we found that the severity of neurological defects
caused by mutations in a gene called Scn8a are determined by another gene,
Scnm1, which is located on a different chromosome," says Miriam Meisler, Ph.D.,
a professor of human genetics in the U-M Medical School. "Scnm1 is expressed
in many human cells, which suggests that it could modify the severity of a
wide range of inherited disorders in humans, including other neurological diseases."
Meisler's research focuses on sodium channel genes that control the flow of
electrical signals between nerve and muscle cells. Mutations in sodium channel
genes produce a variety of neurological disorders — including several types
of epilepsy, ataxia, poor muscle coordination, paralysis and cardiac arrhythmias
like long QT syndrome.
"If we can find a way to change the secondary effects of modifier genes, we
may be able to minimize the impact of the original genetic defect," Meisler
says.
The U-M study was funded by the National Institutes of Health. Meisler conducted
the study with David Buchner, a U-M graduate student, and Michelle Trudeau,
a U-M research associate.
-SFP
Read an expanded version:
www.med.umich.edu/opm/newspage/2003/scnm1.htm
More information on modifier genes:
www.med.umich.edu/genetics/faculty/meislermore.htm
 
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