Molecular genetics and the basic defect causing cystic fibrosis

Recombinant DNA sequences are now available that allow the mapping of the entire human genome, but the first linkage to CF came using classical protein polymorphisms. The enzyme paraoxonase was shown to be loosely linked to CF by the Copenhagen group, to be followed quickly by six cloned DNA sequences: pJ3-11, 7C22, COL1A2, and TCRB (St. Mary's), 917 (Toronto), and met (Salt Lake City). Both pJ3-11 and met are very close genetically to the CF mutation and can be used for carrier detection and prenatal diagnosis in many informative families with a CF child. There is no evidence for heterogeneity of the CF locus. The collection of informative markers surrounding the CF locus is now sufficient to permit attempts to be made to isolate the defective gene using a combination of chromosome-mediated gene transfer, pulse-field gel electrophoresis, cosmid mapping, and chromosome walking techniques, although the difficulty of obtaining tissue in which the defect is known to be expressed remains a problem.