The CF gene: 10 years on

These days everyone is looking for genes. Grant money, media interviews, self-esteem, Nobel prizes, and lots of interesting biology lure researchers into molecular genetics, and diseases as diverse as asthma, chronic obstructive pulmonary disease and lung cancer will soon be mastered by brave new understanding. All true, but will it make any difference? Cystic fibrosis got there first, and 10 years after the discovery of the CF gene it is a good time to take stock. Compared with polygenic diseases, cystic fibrosis is easy and therefore paints the rosiest picture of what can be achieved by genetic research. If the CF gene has helped patients, then the discovery of genes associated with other diseases may do the same. The steps involved in the genetic revolution were well illustrated in a recent review article1 as shown in fig 1. Figure 1 Medical consequences of the human genome project. Reproduced with permission from Collins.1 By sequencing the CF gene, the protein was deduced and found to resemble a family of ATP binding membrane proteins with both ion channel and macromolecule transporter properties. Cystic fibrosis transmembrane conductance regulator protein (CFTR) is a chloride channel which opens in response to phosphorylation by ATP and is found in sweat and pancreatic ducts, gut, seminiferous tubules, and conducting airways—all sites of cystic fibrosis disease.2Interestingly, CFTR is also expressed in the heart, choroid plexus, and renal tubules, organs with normal function in cystic fibrosis. Other properties of cystic fibrosis have been proposed such as the regulation of apical membrane sodium transport in the airways and acidification of intracellular organelles. No transporter function of CFTR has yet been found. Over 800 disease associated mutations of the CF gene have been described; these differ with ethnic origin but only a handful are common. These mutations have …