Discovery of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene

Map of human chromosome 7.

In the early 1980s a number of novel molecular tools were applied to CF to try to map the genomic location of the gene responsible for CF (Mayo, B. J. et al., 1980). With the application of restriction fragment length polymorphism (RFLP) analysis (Kan, Y. W. & Dozy, A. M., 1978) the CF locus was tightly mapped to human chromosome 7q31 (right) (Knowlton, R. G. et al., 1985; White, R. et al., 1985;Wainwright, B. et al., 1986).

A physical map of the region was created by chromosomal walking (Rommens, J. M. et al., 1989) indicating that the gene covered a sequence of around 250,000 base pairs (bp). Two putative transcribed complementary DNA (cDNA) clones from the sequence were used to probe cDNA libraries created from colon carcinoma cell lines, normal and CF sweat gland cells, pancreas and adult lungs. This led to the isolation of 18 further cDNA clones with overlapping sequences that in total spanned 6.1 Kbp and predicted a protein of 1480 amino acids (Riordan et al., 1989)

The sequence shared homology with members of the newly-characterised ATP binding cassette (ABC) superfamily, membrane-spanning proteins capable of transporting ions and other substances (Gros et al., 1986; Higgins et al., 1986; Higgins et al., 1988). The gene was named the cystic fibrosis transmembrane conductance regulator gene (CFTR) encoding the CFTR protein (Riordan et al., 1989).