A long-range restriction map encompassing the cystic fibrosis locus and its closely linked genetic markers

Abstract

The cystic fibrosis (CF) locus has been localized to the long arm of chromosome 7 by linkage analysis, and the genetic relationship between CF and the probes J3.11, met, and 7C22 has been extensively studied. To extend this genetic analysis to higher resolution, to provide information on physical distances underlying the genetic relationships, and to set limits to the position of the cystic fibrosis mutation, we have constructed a partial restriction map covering approximately 5 Mb that defines the physical relationship between these and the more recently isolated markers CS.7, XV-2c, Lcn2, and C2/5. Allelic association indicates that CS.7 and XV-2c are close to the CF locus, and an expressed sequence from this region has been described as a candidate gene for this mutation (X. Estivill et al., 1987, Nature (London) 326: 840-845). Using pulsed-field gel electrophoresis we have determined the physical order of these markers to be cen-7C22-Lcn2-met-C2/5-XV-2c-CS.7-J3.11-tel and have localized the CF mutation to an interval of less than 1500 kb. A (not unexpected) disproportionality was observed between the currently best estimates of genetic and physical distances, with the interval J3.11-met showing an approximately fourfold higher frequency of recombination than the met-7C22 interval.