Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Find Gene Responsible for Neurodegenerative Disease in Dogs, Possibly in Humans

25.08.2010
A North Carolina State University researcher has helped to locate and identify a gene responsible for a fatal neurodegenerative disease that affects American Staffordshire terriers. This same gene may be responsible for a similar rare, fatal disease in humans. Its discovery will lead to improved screening and diagnosis of the disease in dogs and is the first step in working toward a cure for both canines and humans.

Dr. Natasha Olby, associate professor of neurology, was part of a multi-national team of researchers who located the gene responsible for a variant of neuronal ceroid lipofuscinoses (NCL), a family of diseases that result in mental and motor deterioration – and eventually death – in the dogs.

The team’s results were published in the Aug. 17 issue of the Proceedings of the National Academy of Sciences.

NCLs, while rare in humans, are most common in children, although an adult-onset form of the disease – known as Kufs’ disease – does occur. In this adult disease, neurons within the brain gradually die, causing loss of vision, epilepsy, dementia and loss of coordination.

Olby saw the first case of a canine version of adult-onset NCL in American Staffordshire terriers in 2000. Over subsequent years, she found that the disease was a widespread and hereditary problem within the breed, affecting one of every 400 registered dogs. The disease kills the neurons in the cerebellum, which controls balance. Over time, the cerebellum shrinks, motor control deteriorates, and the patient dies or is euthanized.

“The disease became so prevalent because it was a recessive disease with a late onset,” says Olby. “Carriers of a single copy of the mutated gene never develop symptoms, and dogs with two copies of the gene might not show symptoms until five or six years of age, so the mutation was able to take hold in the breeding population.”

Through genetic analysis, the research group was able to locate the specific gene – an entirely novel mutation that has not been reported in people. According to Olby, the novel nature of the mutation means that researchers can now test samples from humans with NCL to determine whether this same mutation causes Kufs’ disease in people.

“The canine disease is a good model of the adult human form of the disease,” says Olby. “We hope that this discovery will provide insight into the development of this disease.”

The Department of Clinical Sciences is part of NC State’s College of Veterinary Medicine.

Note to editors: An abstract of the paper follows

“A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis”

Authors: Marie Abitol, Unite Mixte de Recherche 955 de Genetique Fonctionnelle et Medicale, Institut National de la Recherche Agronomique; Jean-Laurent Thibaud, United Propre de Recherche de Neurobiologie, Unisersite Paris-Est Ecole Nationale Veterinaire d’Alfort; Natasha Olby, North Carolina State University; et al

Published: Aug. 17, 2010, in Proceedings of the National Academy of Sciences

Abstract:
Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs’ disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the Arylsulfatase G (ARSG) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs’ disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.

Tracey Peake | EurekAlert!
Further information:
http://www.ncsu.edu

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>