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Dog genes offer keys to human disease

Date: 27.5.2013 

Berlin, 24 May 2013: For Kerstin Lindblad-Toh, of the University of Uppsala in Sweden, news that the European Union (EU) was to provide funding for a project aimed at using research into canine genetics as a kind of ‘fast-track’ to help provide cures for many important human diseases marked the achievement of a long-held ambition.

As a Professor of Comparative Genomics, who had led the sequencing and analysis of the canine genome project a few years previously, Kerstin knew that dogs provided an excellent model for the study of human diseases and their causes. Dogs suffer from many of the same diseases as humans, including cancer, heart and lung disorders, epilepsy, diabetes, and skin problems. But in dogs these diseases are genetically much simpler to study than in humans. If researchers could understand these simpler canine genetics, not only would it help reduce the high level of inherited canine disease, but the implications for human medicine would be incredibly exciting as well.

The idea of being able to help both Man and his best friend simultaneously was just very appealing to me,” Professor Lindblad-Toh recalls. 

At individual country level, Europe is too fragmented to allow for studies in canine genetics to take place on the necessary scale, she continues. The EU support, provided under the FP7 funding, allowed European canine geneticists and veterinarians to work together on a pan-European scale for the first time and create a research community that equalled, or even surpassed, what was happening in the US.

Taking the Latin word for ‘she-wolf’ as its name – in honour of one of humanity’s most celebrated canine benefactors, the wolf that nursed Romulus and Remus, the twin founders of Rome - the LUPA project brought together partners from 12 European countries. In a major feat of organisation and coordination, the group collected 10,000 DNA samples from purebred dogs from a number of specifically chosen breeds. The focus was on purebred animals because they offer the greatest simplicity in genetic terms.

Within the canine world, each breed has a unique genetic make-up - which means that different breeds are relevant for the study of different diseases. So, for example, LUPA researchers studied the English Springer Spaniel and the Poodle for cancer, the Giant Schnauzer and Hovawart for hypothyroid diseases, and the Great Dane and Doberman for cardio-vascular disorders.

The project even opened up the possibility of treating behavioural disorders, with the Cocker Spaniel being the subject of another line of research, in the hope of understanding more about the genetic roots of aggressive behaviour.  

The idea that canine genetics could help unlock the secrets of human diseases has already led to a number of successes. A mutant gene in Golden Retrievers was identified as being responsible for a skin disorder known as ichthyosis, a generalised scaling of the skin which appears at birth. Analysis of the corresponding gene in human sufferers revealed the same mutation. Old English Sheepdogs, meanwhile, yielded the discovery of a genetic mutation responsible for a rare but serious respiratory disease. Previously, mutations in some ten different genes had been identified as possible causes of PCD (primary ciliary dyskinesis) in humans, but more than 60% of cases had remained unsolved. 

And we have the Lagotto Romagnolo – a breed from the Romagna region of Italy often used as a truffle hunter - to thank for the identification of a new gene associated with epilepsy.

For Professor Lindblad-Toh, the feeling that results from making these discoveries is hard to describe. “It is really exciting when you discover a mutation in a gene with unknown function responsible for a canine disease - and then you find out that mutations in the equivalent human gene are responsible for a similar human pathology,” she says.

But the journey - and the ambition - do not stop with the successes achieved so far. For Kerstin Lindblad-Toh, even greater prizes lie ahead: “With a bit more time, we will be able to pinpoint major genes and pathways involved in cancer development,” she adds.

It seems that dogs really are man’s best friend – in a way no-one could even have dreamed possible just a few years ago. 


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