Researchers from the LUPA Consortium have discovered a new gene responsible for the development of a human respiratory disease thanks to the study of the same illness naturally occurring in pet dogs. Primary ciliary dyskinesis (PCD) is a rare genetic disease affecting one human out 20.000 and characterized by abnormally functioning cellular cilia. Cilia are very abundant at the surface of respiratory airways, when beating they allow the elimination of microorganisms from air. If cilia are immotile or not motile enough affected people develop frequent respiratory infections leading to a progressive loss of lung functions. Mutations in about ten different genes can be responsible for this condition but more than 60% of cases are still unsolved. Animals may develop the same disease.
In 2007 a few Old English Sheepdogs suffering from chronicle bronchitis were examined at the Veterinary Faculty of the University of Liège. The frequency of affected dogs among pedigrees suggests a genetic disease. Moreover one dog presented a situs inversus, an inversion of the heart position. Together with respiratory troubles PCD can lead to organs displacement due to dysfunction of specific motile cilia during embryonic development. The analysis of the genetic material from 5 affected and 15 healthy Old English Sheepdogs led to the discovery of a region on chromosome 34 associated with the development of the disease. Among the 151 genes included in the region ten were coding for proteins involved in cilia function. All the exons were sequenced and a disrupting mutation was discovered in CCDC39 coding for a protein with not yet known function regarding cilia structure and motility.As this gene was not implied in human PCD cases fifty samples from people harbouring similar cilia defects as dogs were screened for mutations in CCDC39. Fifteen different mutations were identified explaining about 5% of all human PCD cases. This study brightly illustrates the ability of the dog model to solve the genetic basis of similar human diseases, the goal pursued by the European project LUPA. The discovery of the implication of CCDC39 in PCD cases will help the genetic counselling of affected families. Regarding dogs a genetic test has been developed to detect Old English sheepdog carriers of the mutation to prevent breeding carriers and giving birth to potentially affected puppies.