Abstract
BackgroundTo determine whether previously reported loci predisposing to nonsyndromic high myopia show linkage to common myopia in pedigrees from two ethnic groups: Ashkenazi Jewish and Amish. We hypothesized that these high myopia loci might exhibit allelic heterogeneity and be responsible for moderate /mild or common myopia.MethodsCycloplegic and manifest refraction were performed on 38 Jewish and 40 Amish families. Individuals with at least -1.00 D in each meridian of both eyes were classified as myopic. Genomic DNA was genotyped with 12 markers on chromosomes 12q21-23 and 18p11.3. Parametric and nonparametric linkage analyses were conducted to determine whether susceptibility alleles at these loci are important in families with less severe, clinical forms of myopia.ResultsThere was no strong evidence of linkage of common myopia to these candidate regions: all two-point and multipoint heterogeneity LOD scores were < 1.0 and non-parametric linkage p-values were > 0.01. However, one Amish family showed slight evidence of linkage (LOD>1.0) on 12q; another 3 Amish families each gave LOD >1.0 on 18p; and 3 Jewish families each gave LOD >1.0 on 12q.ConclusionsSignificant evidence of linkage (LOD> 3) of myopia was not found on chromosome 18p or 12q loci in these families. These results suggest that these loci do not play a major role in the causation of common myopia in our families studied.
Highlights
To determine whether previously reported loci predisposing to nonsyndromic high myopia show linkage to common myopia in pedigrees from two ethnic groups: Ashkenazi Jewish and Amish
Individual families showing linkage Only one Amish family (3061) showed marginal evidence for linkage (LOD > 1.0) to the region previously reported on chromosome 12 (D12S1706 and D12S346) for both two-point and multipoint parametric analyses (Table 5)
Cycloplegic refractions were done on all individuals less than 40 years of age with one drop each of 1% cyclogyl, 1% mydriacyl and 2.5% phenylephrine
Summary
Screening The study protocol adhered to the tenet of the Declaration of Helsinki and was approved by the University of Pennsylvania and the National Human Genome Research Institute, National Institutes of Health institutional review boards. All other individuals were classified as unknown for the trait This ascertainment protocol resulted in the collection of 40 Amish families and 38 orthodox Jewish families. Of the 40 Amish families, phenotype data were available on 340 persons (170 individuals were affected and 170 were unaffected) but only 323 DNA samples were available to be genotyped. For each of the 12 models tested, simulations were performed assuming that the underlying proportion of families linked to the same marker locus (α) was 25%, 50%, 75% and 100%. All persons younger than age 5 were coded as unknown for the trait This analysis assumed autosomal dominant inheritance of a myopia susceptibility allele. The heterogeneity testing was performed separately in the Jewish and Amish families and in a joint analysis of LOD scores from the two datasets combined.
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