Molecular genetics of human myopia: an update

Abstract

Myopia, or nearsightedness, is the most common human eye disorder in the world, and is a significant global public health concern. Along with cataract, macular degeneration, infectious disease, and vitamin A deficiency, myopia is one of the most important causes of visual impairment worldwide. Severe or high-grade myopia is a leading cause of blindness because of its associated ocular morbidities of retinal detachment, macular choroidal degeneration, premature cataract, and glaucoma. Ample evidence documents the heritability of the non-syndromic forms of this condition, especially for high-grade myopia, commonly referred to as myopic spherical refractive power of 5 to 6 diopters or higher. Multiple high-grade myopia genetic loci have been identified, and confirmatory studies identifying high-grade and moderate myopia loci have also occurred. In general, myopia susceptibility genes are unknown with few association studies performed, and without confirmation in other research laboratories or testing of separate patient cohorts.

Figures

Figure 1

The Center for Inherited Research (CIDR) International Family High Myopia linkage study analyses show strong confirmation for linkage of one or more high-grade myopia susceptibility genes to the MYP3 locus at chromosome 12q21–23. The major contributors to this locus with two peaks are from the Duke and Hellerup sites. The Melbourne, Toulouse and Cardiff sites did not have significant linkage to this locus. The strongest consensus linkage region is near 101.97cM, which replicates previous MYP3 locus analyses.

Figure 2

Schematic representation of the arrangement of Opsin gene array and CXorf2 genes on chromosome Xq28 locus source - UCSC genome browser. OPN1LW= opsin 1 low wavelength –red cone pigment gene, OPN1MW =opsin 1 medium wavelength –green cone pigment gene, TKTL1= transketolase-related gene. Vertical bars are exons, horizontal bars are introns, and arrow heads indicate the direction of transcription. A color version of this figure is available online at www.optvissci.com.

Figure 3

(A) Quantification of opsin gene expression by real-time polymerase chain reaction. Expression pattern follows the number of copies previously reported by Young et al 2004. (B) Quantification of CXorf2 gene expression by real-time polymerase chain reaction. All affected males show an expression of up to 5 copies of CXorf2. The calibrator was assigned a value of 3 copies based on and relative to the findings of the number of known copies of opsin gene array.

Figure 4

Array comparative genomic hybridization (CGH) y-axis represents log2 ratio calculated by subtracting the log value of the reference sample intensity from the log of the test sample intensity. R= red opsin gene, G= green opsin gene. A color version of this figure is available online at www.optvissci.com.

Figure 5

Human COL1A1 gene structure. The size of each exon and intron is not to scale. Vertical lines show 8 single nucleotide polymorphisms (SNPs) with their respective public reference SNP rs number from the dbSNP database.