These findings, from a study led Teepu Siddique, M.D., and colleagues at Northwestern University, open the door to investigating gene-environment interactions as a cause of ALS and other illnesses and to the development of molecular targets for specific treatments. The study was published in the August 22 online issue (available now) of the journal Neurology.
Siddique is Les Turner ALS Foundation/Herbert C. Wenske Professor, Davee Department of Neurology and Clinical Neurosciences, professor of cell and molecular biology and director of the Neuromuscular Disorders Program at Northwestern University Feinberg School of Medicine.
ALS is a complex neurodegenerative disorder of the motor neurons that results in muscle weakness, difficulty speaking, swallowing and breathing and eventual total paralysis and death generally within five years.
In 1993 Siddique and collaborators determined that mutations in a gene known as SOD1 account for 20 percent of familial, or inherited, ALS (2 percent of all cases of ALS). However, the cause of sporadic ALS is still unknown.
In earlier research Siddique and other researchers hypothesized that sporadic ALS is modulated by variations in multiple genes interacting with each other and environmental exposures.
The genes for human paraoxanases (PON 1, PON 2 and PON 3), which are located on chromosome 7q21.3, code for the production of detoxifying enzymes involved in the metabolism of a variety of drugs, organophosphate insecticides, such as parathion, diazinon and chlorpyrifos, and nerve gas agents such as sarin.
Previous research described a possible twofold increased risk for developing ALS in veterans of the Gulf War, indicating a war-related environmental exposure to organophosphates and sarin in genetically susceptible individuals as a possible cause. PON gene cluster variants have previously been associated with other neurodegenerative and vascular disorders, including Alzheimer's disease, Parkinson's disease, coronary artery disease and stroke.
Although the Northwestern DNA study samples were not analyzed for inclusion of Gulf War veterans, Siddique and co-researchers found significant evidence that gene variations (polymorphisms) on the chromosome region encompassing PON2-PON3 were strongly associated with sporadic ALS.
"Thus, single nucleotide polymorphism genotyping in the intergenic regions of the PON gene cluster, and replication, gene expression, gene-gene interaction and PON serum/enzymatic studies may help elucidate the complexity of PON cluster association with ALS," Siddique said.
Siddique hopes to study DNA samples from Gulf War veterans with increased incidence of sporadic ALS and has applied for their DNA from the Veterans Administration collection.
Elizabeth Crown | EurekAlert!
Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences