MAPPING THE RP2 LOCUS FOR X-LINKED RETINITIS-PIGMENTOSA ON PROXIMAL XP - A GENETICALLY DEFINED 5-CM CRITICAL REGION AND EXCLUSION OF CANDIDATE GENES BY PHYSICAL MAPPING

Genetic linkage studies have implicated at least two loci for X-linked retinitis pigmentosa [XLRP] on proximal Xp. We now report a defined g enetic localization for the RP2 locus to a 5-cM interval in Xp11.3-11. 23. Haplotype analysis of polymorphic markers in recombinant individua ls from two XLRP families has enabled us to identify DXS8083 and DXS66 16 as the new distal and proximal flanking markers for RP2. Using STS- content and YAC end-clone mapping, an similar to 1.2 Mb YAC contig has been established encompassing the proximal RP2 boundary and extending from TIMP1 to DXS1240 in Xp11.23. Several ESTs have been positioned a nd ordered on this contig, one of which is novel to the region, identi fied by sequence data-base match to a physically mapped YAC insert ter minal STS. Integration of the genetic and physical data has placed fou r retinally expressed genes proximal to DXS6616, and thereby excluded them from a causitive role in RP2. This work now provides a much neede d focus for positional cloning approaches to isolation of the defectiv e gene.