Refined genetic and physical positioning of the gene for Doyne honeycomb retinal dystrophy (DHRD)

Doyne honeycomb retinal dystrophy (DHRD) is a late-onset autosomal dominant disorder that causes degeneration of the retina and can lead to blindness. We have previously assigned DHRD to a 5-cM region of chromosome 2p16 betwe en marker loci D2S2739 and D2S378. Using sequence-tagged sites (STSs), expr essed sequence tags (ESTs) and polymorphic markers within the DHRD region, we have identified 18 yeast artificial chromosomes (YACs) encompassing the DHRD locus? spanning approximately 3 Mb. The YAC contig was constructed by STS content mapping of these YACs and incorporates 13 STSs, including four genes and six polymorphic marker loci. We also report the genetic mapping o f two families with a dominant drusen phenotype to the DHRD locus: and gene tic refinement of the disease locus to a critical interval flanked by micro satellite marker loci D2S2352 and D2S2251, a distance of approximately 700 kb. These studies exclude a number of candidate genes and provide a resourc e for construction of a transcriptional map of the region, as a prerequisit e to identification of the DHRD disease-causing gene and genes for other di seases mapping in the region, such as Malattia leventinese and Carney compl ex.