Introduction: High myopia (>-6.00 diopters) is a complex common disorder that predisposes individuals to retinal detachment, glaucoma, macular degeneration, and premature cataracts. A recent linkage analysis of seven families with autosomal dominant high myopia has identified one locus (MYP2) for high myopia on chromosome 18p11.31 (Young et al.:Am J Hum Genet 1998;63:109-119). Hap-lotype analysis revealed an initial interval of 7.6 centimorgans (cM). Methods: Transmission disequilibrium tests (TDT) with both the Statistical Analysis for Genetic Epidemiology (SAGE) 3.1 TDTEX and GENEHUNTER2 (GH2) programs were performed using chromosome 18p marker alleles for this interval. Results: Using SAGE analysis, the following p values were obtained for markers in marker order in this region: D18S1146 (p = 0.227), D18S481 (p = 0.001), D18S63 (p = 0.062), D18S1138 (p = 0.0004), D18S52 (p = 1.79 × 10-6), and D18S62 (p = 0.141). GH2 TDT analysis revealed the following p values for the best allele for the markers: D18S1146 (p = 0.083), D18S481 (p = 0.108), D18S63 (p = 0.034), D18S1138 (p = 0.011), D18S52 (p = 0.007), and D18S62 (p = 0.479). Conclusion: These data suggest that the gene for 18p11.31-linked high myopia is most proximal to marker D18S52, with a likely interval of 0.8cM between markers D18S63 and D18S52. Due ot the contraction of the interval size by TDT, these results providea basis for focused positional cloning and cadidate gene analysis at the MYP2 locus.
- Autosomal dominant high myopia
- Disequilibrium testing
- Ene mapping