Further refinement of the MYP2 locus for autosomal dominant high myopia by linkage disequilibrium analysis.
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). Haplotype 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 GENEHUNTER 2 (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 x 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 0.8 cM between markers D18S63 and D18S52. Due to the contraction of the interval size by TDT, these results provide a basis for focused positional cloning and candidate gene analysis at the MYP2 locus.
Young, TL; Atwood, LD; Ronan, SM; Dewan, AT; Alvear, AB; Peterson, J; Holleschau, A; King, RA
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