It is here that the dog steps in. Individuals within the same breed being very closely related, the breed can be considered as a single large family. ‘Studying PCD in a breed of dog comes down to studying a genetically homogenous disease. The genetics of diseases within it is comfortably more  simplified in comparison with humans,’ explains the professor.

In the context of the European LUPA project (‘Unravelling common human diseases using dog genetics’), Anne-Christine Merveille, Anne-Sophie Lequarré, Michel Georges and their colleagues set out about taking an interest in the genes responsible for primary ciliary dyskinesia in the bobtail. Several puppies of this breed, suffering from chronic bronchitis, were examined at the clinic of the ULg’s Faculty of Veterinary Medicine. The analysis and comparison of the DNA of bobtails affected by PCD and healthy dogs enabled the identification of a region of canine chromosome 34 linked to this disease. Ten of the 151 genes situated in this region in effect code for the proteins involved in cilia functioning. In taking the analyses further the researchers were able to more precisely put their finger on a mutation of gene CCDC39. ‘In checking if the equivalent gene in humans also had mutations in the families of patients affected by PCD, we realised that these mutations could explain 5 to 10% of the cases of patients suffering from this complaint,’ reveal the researchers. The results of this study have been published in the Nature Genetics journal (1).

From prenatal diagnosis to gene therapy

Once the mutations of CCDC39 had been detected what remained was an understanding of how they affect the movement of vibrant cilia. ‘We could observe that the loss of function of this gene reduces the mobility of the cilia but we didn’t know if that was due to a direct or indirect effect of the mutation.’ Thanks to the functional analyses of gene CCDC39 the researchers succeeded in demonstrating that the components of the inner dynein arms and the dynein regulatory complex (DRC), an important intermediary of ciliary mobility, are linked to the expression of this gene. ‘The CCDC39 gene plays a key role in the assembly of the cilia’s internal structures, and its mutation affects the correct functioning of the inner dynein arms and the dynein regulatory complex,’ point out the researchers. It is in this way that people who have such mutations have a sort of rigidity in the fluttering of their vibrant cilia.

‘The discovery of the genes responsible for PCD has an undeniable clinical impact. The families with this disease often discover it in a brutal manner, with the birth of a child who is affected. Couples often want to know if other children will be affected or not. They don’t want to see a second child suffering in such a way. Thanks to the identification of predisposition genes, they can make use of prenatal diagnosis,’ explains the researchers. In addition, in the longer term the bringing to light of such genes could permit gene therapy to be envisaged. ‘The dog is a privileged model for developing such a therapy’ add the researchers.

Humans are thus now counting on the dog to better understand and treat the diseases which affect them. Besides the impact this approach could have on human health, it also serves veterinary medicine and thus once again tightens a little more the links between humanity and its ‘best friend.’

(1). Merveille AC, Davis EE, Becker-Heck A, Legendre M, Amirav I, Bataille G, Belmont J, Beydon N, Billen F, Clément A, Clercx C, Coste A, Crosbie R, de Blic J, Deleuze S, Duquesnoy P, Escalier D, Escudier E, Fliegauf M, Horvath J, Hill K, Jorissen M, Just J, Kispert A, Lathrop M, Loges NT, Marthin JK, Momozawa Y, Montantin G, Nielsen KG, Olbrich H, Papon JF, Rayet I, Roger G, Schmidts M, Tenreiro H, Towbin JA, Zelenika D, Zentgraf H, Georges M, Lequarré AS, Katsanis N, Omran H, Amselem S. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs. Nature Genetics Volume: 43, Pages:72–78 (2011)