A YAC CONTIG ENCOMPASSING THE RECESSIVE STARGARDT DISEASE GENE (STGD)ON CHROMOSOME 1P

Stargardt disease (STGD) and fundus flavimaculatus are infrequent auto somal recessive conditions characterized by a juvenile macular dystrop hy and variable degrees of peripheral retinal changes. Linkage analysi s performed in 47 STGD/fundus flavimaculatus families demonstrated sig nificant linkage to 13 polymorphic DNA markers on chromosome 1p. The m aximum combined two-point lod score was 32.7 (maximum recombination fr action [theta(max)] = .006) with the polymorphic marker D1S188. Our da ta demonstrate that STGD and fundus flavimaculatus are the same disord er clinically and genetically and provide further evidence for genetic homogeneity of this phenotype. Analysis of recombination events on di sease chromosomes placed the STGD gene within a 4-cM interval between markers D1S435 and D1S236. A physical map was constructed of a YAC con tig flanking STGD, from markers D1S500 to D1S495, and includes the cri tical interval delineated by historical recombinants. This contig span s similar to 31 cM, with one gap (3-5 cM) that is outside the 4-cM cri tical region. Localization of STGD to a single YAC contig will facilit ate its positional cloning.