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. 2012 Jan;4(1):49-59.
doi: 10.18632/aging.100427.

Quantitative Trait Loci on Chromosome 1 for Cataract and AMD-like Retinopathy in Senescence-Accelerated OXYS Rats

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Free PMC article

Quantitative Trait Loci on Chromosome 1 for Cataract and AMD-like Retinopathy in Senescence-Accelerated OXYS Rats

Elena E Korbolina et al. Aging (Albany NY). .
Free PMC article

Abstract

Age-related macular degeneration (AMD) and cataract are common age-related diseases in humans. Previously we showed that senescence-accelerated OXYS rats develop retinopathy and cataract, which are comparable to human AMD and senile cataract. Here we focused on the identification of quantitative trait loci (QTLs), which affect early-onset cataract and retinopathy in OXYS rats, using F2 hybrids bred by a reciprocal cross (OXYS×WAG and WAG×OXYS). Chromosome 1 showed significant associations between retinopathy and loci in the regions of markers D1Rat30 and D1Rat219 (QTL1) as well as D1Rat219 and D1Rat81 (QTL2); and between early cataract development with the locus in the region of the markers D1Rat219 and D1Rat81 (QTL2). To determine the effects of these QTLs, we generated two congenic strains by transferring chromosome 1 regions from OXYS into WAG background. Both congenic strains (named WAG/OXYS-1.1 and WAG/OXYS-1.2, respectively) display early cataract and retinopathy development. Thus, we confirmed that genes located in the analyzed regions of chromosome 1 are associated with the development of these diseases in OXYS rats.

Conflict of interest statement

The authors of this manuscript have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Plots of the distribution of trait linkage probability in the population of F2 rats (bred by reciprocal cross of OXYS and WAG) at age 3-4 months. The linkage of: (panel A) retinopathy; (panel B) cataract with markers on chromosome 1 was analyzed. Dotted vertical line at LOD = 2.0 is the threshold for suggestive statistical significance. The OXYS regions introgressed into WAG rats in the construction of congenic strains are shown as inserts to the left of the linkage map.
Figure 2
Figure 2
The breeding scheme for the construction of congenic strains. Selection is made at microsatellite marker locus M through a series of backcrosses such that the M1 allele of a donor (OXYS) replaces the M2 allele of a recipient (WAG). Rats are genotyped at M by PCR reaction using DNA obtained from tail tips. The genome of the donor strain is shown as an open symbol, and the genome of the recipient strain as a solid symbol. Increasing shades of gray from light to dark represent an increase in the percentage of genetic background of the recipient that occurs with each backcross (BC). The scheme is based on [26].
Figure 3
Figure 3
Cataract and retinopathy incidence in rats of WAG/OXYS-1.1 and WAG/OXYS-1.2 congenic strains at the ages of 1.5-2 and 3-4 months. Data are presented as a distribution of animal eyes with the stages of cataract and retinopathy (colors labeled with 0 through 2 correspond to a stage of cataract or retinopathy).

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