The aim of this project was to map, identify and characterize secondary genetic factors influencing the severity of clinical symptoms in cystic fibrosis, a disease that exhibits significant clinical variability, even between family members. Although some of this variation can be explained by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), the main cause of CF, evidence is growing that secondary environmental as well genetic factors influence the course of the disease.

Together, the Canadian Consortium assembled 2618 cystic fibrosis families consisting of more than 3000 CF patients. These numbers were bolstered with foreign support, which added more than 360 additional families. As a result, Canadian scientists could perform difficult statistical analyses to reveal complex relationships between genes and disease. Over the course of this project, the investigators performed several genetic screens to uncover gene variants linked to relevant clinical phenotypes.

The investigators validated three previously published genetic associations for CF, including the significance of TGF1ß in CF-related pulmonary defects. This important clinical finding was published in the New England Journal of Medicine in October, 2005. Several genetic screens were subsequently performed, uncovering 23 potential candidate genes involved in pulmonary responses. When the project ended, these and other candidates were being evaluated using additional funding from Genome Canada through the Ontario Genomics Institute. The project team also established tissue-culture cell samples for future research, now the world’s largest resource for CF genetic studies.