MND Research breaking news…new gene discoveries

MNDMND Research breaking news…new gene discoveries shed light on motor neurone disease…this is why your donations are so very important..

Breaking news from MND Australia – 27 June 2016

New gene discoveries shed light on motor neurone disease.

Two papers published today in the prestigious journal Nature Genetics provide new insights on the genes predisposing to amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND). Three new genes known as C21orf2, MOBP and SCFD1 have been linked to MND, and a fourth gene, NEK1, has been confirmed as an MND susceptibility gene.
The findings are the result of a huge international effort involving hundreds of scientists and thousands of samples from people with MND. The work of the contributing groups was supported by various grants from governmental and charitable bodies, including the Motor Neurone Disease Research Institute of Australia.

The MNDRIA have prepared a brief explanation about what the latest research means;

This latest finding is a new piece of a complex puzzle. We already know that genetics plays an important role in why some people get MND. Research to date has told us about the genetics of some inherited forms of MND – where there’s a family history of the condition. Familial MND is seen in about 10% of all cases of MND, where more than one family member is affected. This new research has found several new genes associated with sporadic MND. Sporadic MND accounts for about 90% of people with MND, where only one person in a family has had MND. A combination of variations in the newly identified genes (plus other genes yet to be discovered) interacting with lifestyle and environmental factors could contribute to causing MND. Understanding what these new genes do could help to identify potential targets for therapies in the future.

New genes associated with sporadic MND

A study conducted by an international consortium of scientists has revealed three new genes known as C21orf2, MOBP and SCFD1are linked to ALS.

The C21orf2 gene was found to have rare mutations, which increased an individual’s risk of developing ALS by 65 per cent. The exact function of C21orf2 is unknown but it may be involved in cell movement, DNA repair and/or dysfunction of the structures that provide cells with energy.

Two other genes identified in the study, MOBP and SCFD1, will require more extensive studies to fine-map variants in them that cause MND.

About 90% of ALS cases are sporadic. Project MinE was established in 2013 to find both common and rare DNA variations associated with ALS by mining genetic data (www.projectmine.com).

Using genetic information from Project MinE, comprising 15,156 ALS patients and 26,224 healthy controls from 15 countries, the researchers used “snapshot” chip-based genetic data combined with whole genome sequencing of 1,861 individuals to find new genes linked to ALS.

The Motor Neurone Disease Research Institute of Australia (MNDRIA) is funding the next phase of research through the Ice Bucket Challenge Grant awarded in 2015 to Professor Naomi Wray and colleagues for the establishment of the Sporadic ALS Australia (SALSA) consortium. The consortium has implemented identical data and DNA collection protocols in all the major MND clinics in Australia.

The Queensland Brain Institute’s Professor Naomi Wray was involved in the data analysis aspect of the international study.

“This research opens new opportunities to understand a complex and debilitating disease, which currently has no effective treatments.

“The SALSA consortium paves the way for Australians with MND to join international efforts in genetic discoveries as a step towards penetrating the complexity of this terrible disease,” Professor Wray said.

MNDRIA Executive Director Research Janet Nash said the collaborative efforts of researchers around the world, ALS patients and the public had provided vital insight to the mechanisms that lead to ALS.

“We are very hopeful that the discovery of new genes will lead to future therapeutic studies,” Ms Nash said.

To access the journal article

New study confirms NEK1 is a risk gene for familial and sporadic motor neurone disease

An international study has confirmed that variants of the NEK1 gene confer susceptibility to ALS.

NEK1 was implicated in ALS in a study published in the journal Science in 2015 but required further investigation before being conclusively linked to the disease.

Researchers in the current study investigated more than 1,000 individuals from 11 countries including Australia with familial ALS (FALS) and more than 7,000 controls to reveal a significant association between FALS and gene variants that cause loss of function of the NEK1 protein.

Further analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for a particular mutation “p.Arg261His” as well as NEK1 loss of function variants. In total, NEK1 variants were observed in nearly three per cent of ALS cases, demonstrating that it is a major risk factor for ALS.

NEK1 is a multi-functional enzyme that has been linked to several cellular functions including cell movement, DNA damage response and nerve cell morphology. Notably, NEK1 is thought to interact with the C21orf2 gene product, also identified as a risk factor for ALS in Nature Genetics today.
Article from MND Australia

To access the journal article