The major goal of this project is to apply second generation resequencing technology to identify disease causing variants influencing pediatric and adult lung diseases in a collection of two longitudinal population cohorts of cystic fibrosis patients that have been well characterized for a comprehensive set of clinical traits. In Phase I, exome sequencing was performed on 43 cystic fibrosis patients with early Pa infection and 48 cystic fibrosis patients with late Pa infection to identify variants influencing the time to onset of Pa infection. In Phase II, additional exomes were added to the study, to reach a total of 91 individuals with early Pa infection and 96 with late Pa infection. The majority of the 340 subjects of Phase II do not have a Pa infection phenotype, but instead have a pulmonary function phenotype (121 severe vs. 124 mild impairment) as determined by the survival corrected Kulich FEV percentile of Corey et al. A small minority have intermediate phenotypes and/or show severe decline in lung function during childhood.

NHLBI GO-ESP: Lung Cohorts Exome Sequencing Project (Cystic Fibrosis)

Exome sequencing identifies the cause of a Mendelian disorder

Exome sequencing as a tool for Mendelian disease gene discovery

Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies.

Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis