Cystic fibrosis (CF) is the most common autosomal recessive disorder in the 
Caucasian population, affecting approximately 1 in 2,000 newborns but the actual 
estimate varies with the geographic location. The incidence of CF in 
non-Caucasian populations is low. Intensive efforts using genetic linkage 
information ultimately led to the cloning of the CF gene prior to the 
identification of the gene product or its function. The gene encodes what is 
believed to be a transmembrane protein, which has been named the cystic fibrosis 
transmembrane conductance regulator (CFTR). The CFTR contains two 
nucleotide-binding folds (NBF) which show homology to numerous transport 
proteins with the greatest homology to the P-glycoproteins that are encoded by 
the multiple drug-resistance loci. A three- base deletion resulting in the loss 
of phenylalanine residue (delta F508) in the tenth exon of the CFTR gene is the 
mutation occurring on the majority of CF chromosomes. The overall frequency of 
delta F508 in the present mutant CF gene pool is about 70%, but the study 
populations are not equally represented: there is marked variation in the 
population of delta F508 among different geographic populations. Recently, 
numerous additional, less common mutations have been found. Some mutations occur 
on 2-5% of the CF chromosomes. Many of these are rare 'private' mutations, 
occurring in individual families of all racial and ethnic backgrounds. By 
contrast over 80% of Western European CF mutations have been identified. The 
highly heterogeneous nature of the remaining CF mutations provides important 
insights into the structure and function of the protein, but further 
improvements are needed in DNA-based genetic screening for CF carrier status.