Cystic fibrosis is an autosomal recessively inherited disease, which is characterized by multiple abnormalities in the production of body secretions. The relative impermeability of sweat glands to chloride ions has been developed as a diagnostic test for cystic fibrosis. The cumulative evidence suggests that chloride transmembrane transport may be the primary defect of the disease. Recently we have cloned and characterized mouse erythrocyte band 3 and a human non-erythrocyte anion transport protein cDNA. We intend to use those two cDNAs to isolate related cDNAs from a liver cDNA library, and then use the different cDNAs to examine RNA by Northern Blot analysis from different cells and tissues in particular those tissues which are affected by cystic fibrosis. RNA species detected in these experiments will be cloned as cDNAs which will be sequenced and used to isolate their corresponding genomic clones. The cloned genes will be used to identify restriction fragment length polymorphisms (RFLPs) associated with the anion transport (AT) genes. The presence or absence of such RFLPs in the DNA of families afflicted by cystic fibrosis will determine whether the AT genes are closely linked with the disease. The AT genes will be mapped by somatic cell genetics and Southern blot analysis. Subsequently, the characterised AT clones will be used to identify the genetic lesions in the AT gene in cystic fibrosis patients. This information will enable us to design probes for diagnosis of the disease and detection of carriers of the disease and would be invaluable in prenatal testing and genetic counseling.
