The contribution of genomics

Duhayer_RC

Molecular genetics has come on leaps and bounds in the past decade, as new tools, methodologies and disciplines like bioinformatics have been developed. These advances have enabled processing and analysis of increasingly large data sets, which has led to faster result generation. Nature published the dog’s complete genome sequence, principally achieved by the BROAD Institute (Boston, MA, United States) headed by Kerstin Lindblad-Toh. Dogs joined humans, mice, rats and chimpanzees on this list of genomes of which we now have very in-depth knowledge. But why did we choose the dog rather than another mammal and what advances has this sequencing opened the way to, and what will the future hold?

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The excesses of genetic manipulation

Down the centuries – especially in the past 300-400 years – humans have had a huge impact on selective breeding, crossing dogs to produce more than 300 breeds. In anatomical terms, these crossings have produced more diversity than is seen in any other species of mammal.

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Unfortunately, when you perform selective breeding based on phenotypic and behavioural traits you also select morbid homozygous alleles responsible for numerous genetic diseases. As a consequence, most dog breeds – each of them being more or less a genetic isolate – suffer from diseases that affect either that particular breed or a group of related breeds. This unfortunate situation, which worries all dog lovers be they breeders, veterinarians or owners, is an opportunity for medical genetics. Three key reasons for this are: firstly, many of these diseases also affect humans; secondly, we know more about dog diseases than about diseases affecting any other animal species; and thirdly, dogs live with humans and so are subjected to the same environmental conditions.

Increased prevention

These considerations have raised awareness of the unique importance dogs can have as a particularly favourable genetic model for identifying morbid gene alleles. This is not only an opportunity for medical genetics, but for veterinary medicine as well. Up until a few years ago the veterinary bibliography mostly comprised clinical cases regarding rare genetic diseases with particular symptoms and treatments. Genetic research is now opening the door to predictive medicine, with the possibility of prescribing genetic screening and improving monitoring of dog populations with the development of genetic identification tests. 480 canine genetic diseases have now been indexed.

Genetic tests can thus be conducted to confirm a diagnosis if the animal presents with the symptoms of a specific disease or as a form of screening, particularly in breeding kennels. These genetic tests make it possible to establish the status with respect to a specific disease of an animal of a breed for which the test has been approved, based on the mutation in a given gene. Breeders can use the results as an extra criterion for selecting breeding stock alongside morphological and behavioural criteria.

New studies

In January 2008, the European Commission launched a project to find animal models other than rodents to study complex human genetic diseases. Twenty-two partners are involved in the four-year Lupa project to collect blood from 8,000-10,000 dogs suffering from one of the 18 genetic diseases selected by the project designers.

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These diseases are split into five groups: cardiovascular diseases, cancers, neurological disorders (primarily epilepsy), inflammatory problems such as diabetes and eczema, and monogenic diseases. The first stage in the project is the collection of blood samples, which is followed by genotyping, in which each of the samples is characterised for 50,000 markers. The final stage is the comparison of the marker genotypes of affected dogs with those of healthy dogs. Various genetic mapping techniques will then be used to gradually and precisely localise the genes responsible for the diseases in the study. Blood will not be collected from laboratory animals, but from sick animals examined by veterinarians (twelve veterinary schools from around Europe will participate in collecting blood samples).

The consequences of the study will be two-fold. In veterinary medicine, it will help verify the predisposition of certain dogs to developing genetic diseases so that the necessary measures can be taken, such as eliminating them from breeding programmes, providing a diet to slow down the development of the disease in question and designing preventive treatment. In human medicine, the results could be extrapolated to humans. Studies of the same type have been conducted on the human genome, but the great diversity of human genomes compared with dog genomes is a major complicating factor, which among other things demands recourse to 5,000 sick and 5,000 healthy humans, rather than the 200 sick and 200 healthy dogs required in the Lupa project. This is why human medicine is placing so much hope in man’s best friend.

© Diffomédia/Royal Canin
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The contribution of genomics
    The contribution of genomics

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