Molecular Phenotypes for Cystic Fibrosis Lung Disease

BACKGROUND:

Cystic fibrosis (CF) is a recessive genetic disorder caused by mutations in CF transmembrane
conductance regulator (CFTR) gene. CF has multi-organ involvement, but respiratory disease is
the major cause of morbidity and mortality. The median age of survival in CF is only 37
years, but there is a broad range of disease severity in the lung, even among patients with
identical CFTR genotypes, including deltaF508 homozygotes.

DESIGN NARRATIVE:

This project holds great promise for defining a robust molecular phenotype for CF lung
disease, which relates to prognosis, and new targets for therapy. By using a large and
well-defined population of deltaF508 homozygotes who also have whole genome single nucleotide
polymorphism (SNP) data, and by studying gene expression across the whole transcriptome in a
large number of samples of two relevant tissues (respiratory epithelium and transformed
lymphocytes), we will be uniquely positioned to develop an integrated view of molecular
mechanisms underlying CF lung disease severity.

Inclusion Criteria:

- Diagnosed with CF

- Participation in Genetic Modifiers of CF Lung Disease study (NCT00037765)

Exclusion Criteria:

- History of lung transplant

- Fully anticoagulated or clotting abnormalities

- Large nosebleed in the last 2 months

- Acutely ill