EU project LUPA uses dogs to piece together human genetic disorders puzzle
Scientists have been relentless in the pursuit to unlock the mystery behind genetic disorders but the complexity of their underlying causes has made it difficult to get answers. For a group of researchers, dogs may hold the key to the solution. While dogs are less genetically complex, they suffer from the same diseases as humans. The LUPA project, named after the female-wolf that fed the twin founders of Rome, is backed by the EU with EUR 12 million and will end in 2012.
The project partners from 12 European countries will collect 10 000 DNA samples and genome wide association (GWA) data from purebred dogs that are either healthy or suffering from diseases that also affect humans.
More than 200 genetic diseases have been reported in recent years. The dog population is made up of 400 purebred breeds, with each breed being a genetic isolate with unique characteristics.
The lower genetic complexity is brought on by the result of inbreeding, and single-nucleotide polymorphism (SNP) markers required to carry out entire genome scans is split by at least 10. SNPs are DNA sequence variations occurring after a single nucleotide in the genome sequence is altered.
The researchers, experts in the field of genomics, will compare the genome of affected dogs to the genome of healthy ones of the same breed. They will target the genes responsible for at least 18 disorders, such as cancer and heart disease. These disorders are outlined in five Work Packages (WPs). WP1 describes four cancers; WP2 three cardiovascular disorders; WP3 four inflammatory disorders; WP4 neurological disorders; and WP5 simple (monogenic) disorders.
'We have decided to focus on certain areas and to standardise the characterisation of these diseases,' said Professor Leif Andersson of Uppsala University in Sweden. The research team will use the DNA from the different breeds of animals in several countries.
'Once they have found the gene, they plan to see what role it plays in humans,' explained LUPA project leader Professor Michel Georges from the University of Liege in Belgium.
Breeds participating in the project include the Golden Retriever and German Shepherd for cancer, the English Cocker Spaniel for aggressive behaviour, and the Doberman and Boxer for hypothyroid diseases. Dogs included in the cardio-vascular disorders group include Great Danes and the Irish Wolfhound, while the Greyhound and Collie are part of the monogenic disorders package.
The DNA samples will be transferred to a centralised, high-throughput SNP genotyping facility, which will store and make the genotypes available for the researchers involved in the project.
The analysis of the genome of the affected dogs will help the researchers identify the genes involved in the mechanisms of these diseases, and gain more insight into the pathways of the pathology, the group said.
The results obtained in LUPA will benefit human medicine and advance medical research. The dog model being used in LUPA will play a key role in improving the understanding of the pathogenesis of common human diseases.
Also participating in LUPA are Denmark, France, Germany Norway, Switzerland and the UK.