Using a new gene sequencing method, a team of researchers from Johns Hopkins and the National Institutes of Health has discovered a gene that appears to cause some instances of familial amyotrophic lateral sclerosis ( ALS ).
The finding could lead to novel ways to treat the more common form of this fatal neurodegenerative disease, which kills the vast majority of the nearly 6,000 Americans diagnosed with ALS every year.

Researchers don’t know exactly what causes ALS, which destroys the motor neurons that control the movement of all the body’s muscles, including those that control breathing. However, studies into the familial form of the disease, which affects 5-10% of those diagnosed with the disease, could shed some light on why motor neurons die in all types of amyotrophic lateral sclerosis.

Researchers were already aware of a handful of genes that appear to cause some cases of familial amyotrophic lateral sclerosis. In the new study, published in the journal Neuron, Bryan J. Traynor, at the Johns Hopkins University School of Medicine and chief of the Neuromuscular Diseases Research Group at the National Institutes of Health, and his colleagues used a new technique known as exome sequencing to search for more. This new technique differs from the more common type of gene sequencing since it focuses only on the 1-2% of the genome that codes for proteins and ignores the remaining, non-coding DNA. Exome sequencing also sequences thousands of genes at the same time, rather than the step-by-step sequencing of the more traditional method, making exome sequencing significantly faster.

Traynor’s team worked with two affected members of an Italian family discovered by colleague Adriano Chiò, of the University of Turin and by Jessica Mandrioli, of the University of Modena. Using exome sequencing on these two ALS patients and 200 people without the disease, the scientists looked for gene differences that the ALS patients had in common that differed from the other samples. Their search turned up a gene called VCP, short for valosin-containing protein.

When the researchers looked for other instances in which this gene was mutated in 210 additional ALS patients, they found four different mutations that affect VCP in five individuals. None of these mutations were found in the genomes of hundreds of healthy controls, suggesting that VCP is indeed the cause for some of the ALS cases.

Though the scientists still don’t know exactly how mutated VCP might lead to amyotrophic lateral sclerosis, they do know that this gene plays a role in a process known as ubiquination, which tags proteins for degradation. A glitch in this process could lead to too much or too little of some proteins being present in motor neurons, leading to their death.

Source: Johns Hopkins, 2010

XagenaMedicine2010


Link: Xapedia - Medical Encyclopedia