In the first genomewide search for the genetic roots
of the most common form of amyotrophic lateral sclerosis,
Johns Hopkins scientists have newly identified 34 unique
variations in the human genetic code among 276 unrelated
subjects with ALS.
The 34 so-called single nucleotide polymorphisms, or
SNPs, represent good candidate genes predisposing people to
the noninherited form of the fatal neurodegenerative
"Although we haven't located the exact gene
responsible for sporadic ALS, our results seriously narrow
the search and bring us that much closer to finding what we
need to start developing treatments for the disease," said
Bryan J. Traynor, of the Department of
Neurology at the School of Medicine.
ALS, also known as Lou Gehrig's disease for the
legendary Yankee first baseman who succumbed to its
paralyzing assault on the nervous system, kills 10,000
Americans a year. An estimated one in 2,000 people is at
risk of developing the disease.
Genes behind inherited forms of ALS--responsible for
about only 5 percent of all cases--were discovered a decade
ago, but no genetic roots had been found for sporadic ALS,
which occurs in people without a family history of the
In the Johns Hopkins study, described in the online
version of Lancet Neurology this month, Traynor and his
team scanned the entire genome of 276 adult male and female
subjects with sporadic ALS and 271 adult male and female
subjects with no history of neurological disease.
Researchers used a new technology known as "SNP chips"
to analyze all 555,352 SNPs in the genome of each subject.
SNP chips are glass slides that resemble computer processor
chips. They're coated with tiny beads that "read" the SNPs
scattered throughout the human genome.
The researchers found 34 genetic variants that ALS
patients were more likely to have compared to normal
individuals without the disease.
"This is the first major step toward understanding how
genetics may influence the most common form of ALS," said
co-researcher Jeffrey D. Rothstein, professor in the
Department of Neurology. "The results will not only help us
to better understand sporadic ALS but also to tailor tools
that will reveal therapies for it."
Traynor cautioned that the 34 SNPs are not guaranteed
trail markers for ALS genes. "If you roll dice 555,352
times, you are bound to get lucky by chance alone on some
of those throws," he said. "The next step is to go back and
figure out which of these 'hits' are real and which are
Thousands of other SNPs were more weakly associated
with ALS, some of which could turn out to be just as
important as those more strongly linked.
Traynor says a follow-up study is in the works that
will replicate the research using a similar number of
patients and controls. Traynor, who has a joint affiliation
with the National Institute of Mental Health, collaborated
in this study with lead author Jennifer Schymick and fellow
researcher John Hardy, both of the Laboratory of
Neurogenetics at the National Institute on Aging.
Researchers from the National Institutes of Health, the
Packard Center for ALS Research at Johns Hopkins and the
University of Turin, Italy, also contributed to this
This study was supported by funding from the National
Institute of Neurological Disorders and Stroke, the Packard
Center for ALS Research at Johns Hopkins and the ALS