Estimation of the physical distance between major genomic markers in the Werner syndrome locus (8p11.2-12) by dual-color fish analysis.

The gene responsible for Werner syndrome (WS) is considered to be located between D8S131 and D8S87 in the 8p11.2-12 region that includes the closest marker D8S339 (Goto et al. (1992) Nature 355: 735-738). In this experiment, the order of major markers in this region was determined and the physical distances between them were estimated by dual-color fluorescence in situ hybridization (FISH) using P1, PAC and cosmid clone DNAs as probes. The fine overall order of telomere-D8S131-D8S339-GSR-PP2A beta-D8S283-D8S87-centromere was determined for the first time. The distance from D8S131 to D8S87 was estimated to be 1,634 kb. To our surprise, the distance between D8S131 and D8S87 is much shorter than previously estimated by recombination analysis, 8.3 cM equivalent to 8.3 Mb in physical distance. These information provide the basis for the positional cloning of WS gene and the identification of its mutation.