Further refinement of the MYP2 locus for autosomal dominant high myopia by linkage disequilibrium analysis.
BACKGROUND
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).


CONCLUSIONS
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
T L
TL
Department of Ophthalmology, University of Minnesota Medical Center, Minneapolis, Minnesota, USA. youngt@email.chop.edu
Atwood
L D
LD
Ronan
S M
SM
Dewan
A T
AT
Alvear
A B
AB
Peterson
J
J
Holleschau
A
A
King
R A
RA
D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D005799:Genes, Dominant; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D009216:Myopia / Q000235:genetics*; D010375:Pedigree; D020161:Physical Chromosome Mapping
D005819:Genetic Markers