Refinement of the RP17 locus for autosomal dominant retinitis pigmentosa, construction of a YAC contig and investigation of the candidate gene retinal fascin

The RP17 locus for autosomal dominant retinitis pigmentosa has previously b een mapped to chromosome 17q by linkage analysis. Two unrelated South Afric an families are linked to this locus and the identification of key recombin ation events assigned the RP17 locus to a 10 cM interval on 17q22. The work reported here refines the mapping of the locus from a 10 cM to a 1 cM inte rval between the microsatellite markers D17S1604 and D17S948. A physical ma p of this interval was constructed using information from the Whitehead/MIT YAC contig WC 17.8. Sequence-tagged site (STS) content mapping of seven ov erlapping YACs from this contig was employed in order to build the map. A B AC library was screened to cover a gap in the YAC contig and two positive B ACs were identified. Intragenic polymorphisms in the retinal fascin gene pr ovided evidence for the exclusion of this candidate as the RP17 disease gen e.