Physical mapping and YAC-cloning connects four genetically distinct 4qter loci (D4S163, D4S139, D4F35S1 and D4F104S1) in the FSHD gene-region.

We have constructed a long-range restriction map of the region on chromosome 4q that contains the gene for facioscapulohumeral muscular dystrophy (FSHD). This region contains the linkage group cen ... D4S163-D4S139-D4F35S1-D4F104S1-FSHD ... 4qter, which spans a genetic distance of about 5 cM. Pulse field gel electrophoresis (PFGE) mapping indicated that these loci span a region not more than 1 Mb. STSs were developed for several of these loci, which served to isolate four overlapping yeast artificial chromosomes (YACs). These YACs confirmed the PFGE map and have allowed us to generate a more detailed restriction map using cosmid contig mapping. The physical distances were smaller than was expected on the basis of the genetic map. Two potential HTF islands have been detected within the cloned region. One HTF island maps about 100 kb centromeric from the tandem repeats involved in the FSHD mutation, whereas the other maps within these tandem repeats.