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 been mapped tochromosome 17q by linkage analysis. Two unrelated South African families are linked to thislocus and the identification of key recombination events assigned the RP17 locus to a 10cMinterval on 17q22. The work reported here refines the mapping of the locus from a 10cM to a1cM interval between the microsatellite markers D17S1604 and D17S948. A physical map ofthis interval was constructed using information from the Whitehead/MIT YAC contig WC 17.8.Sequence-tagged site (STS) content mapping of seven overlapping YACs from this contig wasemployed in order to build the map. A BAC library was screened to cover a gap in the YACcontig and two positive BACs were identified. Intragenic polymorphisms in the retinal fascingene provided evidence for the exclusion of this candidate as the RP17 disease gene.Keywords: retinitis pigmentosa; RP17; fine mapping; YAC contig; retinal fascin