Wednesday, August 10, 2011

Dog Gene May Lead To Cure For Childhood Epilepsies

A new epilepsy gene found by an international team of EU-funded researchers in Lagotto Romagnolo dogs, known for their gift for truffle hunting, could be a new candidate gene for human benign childhood epilepsies characterised by seizure remission. The gene, LGI2, was found by an international team led by scientists from the University of Helsinki and the Folkhälsan Research Center in Finland.

Lagotto Romagnolo 
Illustration of this article
Although dogs are less genetically complex than humans, they suffer from the same diseases; any discoveries made by scientists about a dog's gene could be relevant to human health too.

This finding was made as part of research supported by almost EUR 12 million of funding from the European Commission through the 'Unravelling the molecular basis of common complex human disorders using the dog as a model system' (LUPA ) project, part of the Seventh Framework Programme 's (FP7) 'Health' Theme.

The LUPA project, which started in 2008 and will run until the end of 2011, brings together veterinary practitioners and scientists from 12 European countries. The team's overall aim is to collect DNA samples from large numbers of dogs suffering from a range of diseases to which humans are also susceptible. Identifying susceptibility genes for common human diseases is tricky due to the complexity of the underlying causes. Some 400 purebred breeds make up the dog population: each one is a genetic isolate with unique characteristics resulting from persistent selection for desired attributes or from genetic changes and inbreeding.

Writing in the journal PLoS Genetics, Professor Hannes Lohi, an author on the study outlining these latest findings from the LUPA project, explains how the discovery is significant for both dogs and humans:
'Every third Lagotto Romagnolo carries the gene mutation in its genome and we have now developed a gene test to be used by breeders to eliminate the disease from the breed. Furthermore, the gene has not previously been linked to human epilepsies, which makes it a new candidate gene for especially childhood epilepsies.'

Lagotto Romagnolo 
File:Lagotto Romagnolo.jpg
Credit: Wikipedia

Epilepsy is the most common neurological disease among children, with 0.5 percent of all children between the ages of 2 and 10 suffering from the condition. During childhood, nerve development in the brain is at its strongest, and epilepsies are characterised by remission; this means that the seizures set in and last for a while before they disappear completely.

An epileptic seizure is caused by an electronic disturbance in brain function. Epilepsies form a heterogeneous group of syndromes of the nervous system in which the causes, the age of onset and the treatment vary significantly. Epilepsy is most common among those on opposite ends of the age spectrum: young children and the elderly.

The exact mechanisms that trigger remission still remain unknown, and this discovery of the new dog gene by the scientists could help researchers better understand how children's brains develop, as well as shed light on remission mechanisms in childhood epilepsies.

'With this study, we gain crucial insight into the pathways and mechanisms that control the development of a child's brain, optimising its structure for electrical stability and seizure-freedom in the rest of adult life. This study will open vast avenues of research in uncovering the molecular bases of the transformation of the brain from its immature state in infancy to its maximal abilities in adolescence and early adulthood,' says Dr. Berge Minassian, another study author based at The Hospital for Sick Children in Toronto, Canada.

Epilepsy is the most common disease of the nervous system in dogs, and different types of hereditary epilepsy exist in many breeds. Previous studies carried out by Professor Lohi uncovered the first canine epilepsy gene, EPM2B, in the Miniature Dachshund. The newly identified mutation in the LGI2 gene is the first idiopathic epilepsy gene in dogs.

Another study author, Eija Seppälä, comments on the findings: 'We tested the mutation in about 40 different breeds and in dogs with a very early age of onset of epilepsy, but it was present only in Lagottos. On the other hand, the study revealed another form of epilepsy in the breed, unconnected with this mutation and with an age of onset in adulthood. In addition, the breed has a progressive juvenile ataxia (lack of motor coordination) with similar onset and symptoms to juvenile epilepsy except that it does not remit - ataxic puppies have to be euthanised usually by the first year of life. More samples are needed for both adult-onset epilepsy and ataxia to enable us to investigate their genetics further.'

Professor Lohi comments on the opportunities this study brings: 'We also study the epilepsies in other breeds, and several new epilepsy loci have been discovered recently. I believe that there will be more similar success stories such as the case of the truffle dogs in future. Canine epilepsies are natural, spontaneous and resemble human epilepsies, offering us a great opportunity to advance ... epilepsy research for the benefit of both humans and dogs.'

Source:
University of Helsinki

Citation: Seppälä, E. H. et al. (2011) LGI2 Truncation Causes a Remitting Focal Epilepsy in Dogs. PLoS Genetics. DOI:10.1371/journal.pgen.1002194.

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