ABSTRACT
I. Introduction The biology of cystic fibrosis (CF) is quite complex, involving multiple organ systems and tissue types. In addition to the primary cellular and physiologic dysfunctions caused by the absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) protein, there are clearly temporal components and environmental factors that contribute to the clinical phenotype. Most patients succumb to the complications of pulmonary disease, but even the pulmonary disease is complex in its etiology and consequently it is not at all clear where the most effective therapeutic targets might lie. One approach for finding those targets is to compare patients with milder attributes of the disease to those with more severe manifestations, and to identify the sources of this variation. Once these sources are identified, the mechanisms behind the variation may be studied and clinical applications developed (e.g., pharmaceuticals), which would target and exploit these mechanisms to effect clinical improvement. Here we discuss genetic approaches to identify genes that modify CF disease severity.
