Genetic and physical location of the gene for Stargardt`s disease and further evidence for genetic homogeneity

Stargardt`s disease is inherited as an autosomal recessive condition characterized by a juvenile macular dystrophy. Genetic linkage analysis recently assigned the disease locus to chromosome 1p21-p13 with the best estimate for location of the gene near the locus D1S435. We performed linkage analysis in 34 North American families and 2 inbred families from the Kingdom of Saudi Arabia with 12 highly polymorphic markers on chromosome 1p flanking D1S435 between D1S207 and D1S223 and report significant linkage for all 12 markers with no evidence for genetic heterogeneity. Two-point linkage analysis demonstrated the Stargardt`s disease locus and D1S435 are linked with a maximum lod score of 17.17 at a recombination fraction of 1%. The markers UT851, D1S188, D1S424, UT2069, and D1S236 also demonstrated recombination fractions of 1% or less with two-point lod scores of 15.86, 21.93, 16.41, 20.36, and 17.37, respectively. To characterize this region further, fifty-five YACs with an average length of 1,118 kb were assembled from the CEPH megabase YAC library to establish a physical map for subsequent efforts to clone this gene. A YAC contig containing the genetic markers UT851, D1S188, D1S424, UT2069, D1S435, D1S236, D1S497, D1S420, UT5782, D1S206, and D1S223, has been constructed covering at least 11 cM.more » The genetic mapping data places the Stargardt`s disease locus between the markers UT851 and D1S435, suggesting that the Stargardt`s disease gene is present on this YAC contig.« less