Fine mapping of the cystinosis gene using an integrated genetic and physical map of a region within human chromosome band 17p13.

The cystinosis gene has been reported to reside in a 3.1 cM region of chromosome 17p13 flanked by markers D17S1828 and D17S1798. We created a yeast artificial chromosome (YAC) contig between these markers and report here an integrated genetic and physical map which will aid in the identification of other genes in this area. Using one pertinent YAC clone, 898A10, we identified new polymorphic markers in the cystinosis gene region. One such marker, D17S2167, was localized by radiation hybrid analysis to within 10.2 cR8000 of D17S1828. Haplotype analysis in two separate informative families revealed recombination events which placed the cystinosis gene between markers D17S1828 and D17S2167, an area estimated to be 187-510 kb in size. This dramatic narrowing of the cystinosis gene region permits the creation of a P1 or cosmid contig across the area of interest. The ultimate cloning of the cystinosis gene should eventually reveal how a functional lysosomal transport protein is synthesized, targetted, processed, and integrated into the lysosomal membrane.