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E. D. Simmons, B. Appukuttan, N. Landauer, M. Neuringer, M. Klein, J. T. Stout, P. Francis; Sequence Analysis of Human AMD Susceptibility Genes in an Aged Nonhuman Primate Population. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5094.
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Age-related macular degeneration (AMD) is a complex disease in which both genetic factors and environmental exposures determine susceptibility. Recently, single nucleotide polymorphisms within the putative gene LOC387715 and the adjacent HTRA1 gene have been associated with increased risk of AMD development in humans. Our aim was to sequence these genes and identify disease-related polymorphisms in a rhesus monkey population that develops age-related drusenoid maculopathy.
Retinal color stereo-photographs were used to classify the severity of drusen in an aged population (17-29 years) of rhesus monkeys (Macaca mulatta). Genomic DNA was isolated from peripheral blood. Consensus human and chimp primers were designed to pertinent regions of the LOC387715 and HTRA1 genes. PCR-based sequencing of these genes was performed on affected monkeys with (a) >20 hard drusen and (b) at least one soft drusen. Results were compared with a control group with <3 small hard drusen. Human gDNA was used as a positive control.
Consensus primers for the LOC387715 sequence gave amplified products of the expected size from rhesus gDNA. Sequence analysis from animals with hard drusen, animals with soft drusen and controls showed that all animals possessed the GCT nucleotides at predicted codon 69, and none were polymorphic for the AMD susceptibility loci. Consensus HTRA1 promoter primers amplified correct products from human gDNA but not from rhesus gDNA.
Although the LOC387715 codon 69 was conserved from rhesus to human, none of the monkeys tested possessed the previously described LOC387715 polymorphism associated with AMD. Unlike LOC387715, our results suggest that the HTRA1 promoter region may have diverged within the primate lineage. Further investigations are warranted to investigate other loci that may influence development of age-related maculopathy in this nonhuman primate population.
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