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The Contribution of Genetic Modulators of Disease Severity in Cystic Fibrosis to other Diseases with Similarities of Clinical Phenotype


Generating solutions




Competition III

Genome Centre(s)



Project Leader(s)

Fiscal Year Project Launched


Project Description

Canada is a world leader in research on cystic fibrosis (CF). Drs. Peter Durie, a pediatrician and senior scientist and Julian Zielenski a geneticist at the Hospital for Sick Children’s Research Institute plan to build on this research strength, by investigating the genetics of other diseases with similar phenotypes – observable physical characteristics, which may be genetically determined.

Drs. Durie and Zielenski are project leaders of The contribution of genetic modulators of disease severity in cystic fibrosis to other diseases with similarities of clinical phenotype. This project will apply knowledge about the genetic factors (so called modifier genes) that influence the severity of CF to other diseases that are clinically similar to CF. These diseases include a single­gene disorder affecting the liver (a1­antitrypsin deficiency), and multifactorial conditions such as pancreatitis due to alcohol abuse and chronic obstructive pulmonary disease due to smoking.

The project will analyse mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) as well as selected modifier genes that are found to influence the severity of disease in patients with CF as well as blood­circulating proteins, in order to identify disease biomarkers, which can help predict disease severity and progression. Diagnostic and prognostic tests will be developed, and genetic test­based risk identification could lead to behaviour modification and disease prevention among those at risk for the diseases. Enormous human suffering and prohibitive healthcare costs are associated with alcohol abuse and tobacco smoking.

This project is expected to yield results of worldwide importance, such as development of genetic tests of disease susceptibility that will be useful in future research projects and in development of preventative strategies to modify behaviour in high risk populations. This in turn should lead to reduced morbidity and mortality and more efficient healthcare. Important components of the project are ethical issues associated with genomics research, as well as industrial, economic and social benefits.


Integrated GE3LS Research: Reporting genetic research results: Perspectives of study participants and researchers
GE3LS Project Leaders: Robin Hayeems, University of Toronto

Several recent commentaries argue that researchers bear an obligation to report genetic research findings to study participants. The nature and scope of this obligation remains disputed and unresolved. While the principles of respect for persons, reciprocity, and beneficence are fundamental to the research enterprise, they may neither be well served if results are disclosed nor denied if they are not disclosed. This integrated GE3LS research examines study participants’ and researchers’ perspectives on how to manage genetic research results with respect to this putative obligation.

Phase 1 of this research surveyed research participants from the Canadian Consortium for Cystic Fibrosis research regarding the meaning ascribed to a recent gene modifier finding reported in the academic literature. One key finding was that study participants expect researchers to share genetic research results with them. Phase II of this research involves a complex experimental design that aims to understand the factors influencing researchers’ judgments regarding reporting results. Using a cross sectional factorial survey design that includes vignettes presenting hypothetical scenarios involving genetic research findings to investigators engaged in cystic fibrosis and autism genetics research, this research aims to better understand the factors that influence researchers’ judgments about:

  1. Informing individuals about genetic research findings,
  2. the clinical significance of a hypothetical research finding,
  3. the nature of a research obligation to re-contact study participants with updated information about a particular finding,
  4. and the nature of a clinical obligation that may/may not ensue from reporting research findings.

Taken together, findings from this integrated research will inform the governance of this important research ethics issue.