Mapping of a macular drusen susceptibility locus in rhesus macaques to the homologue of human chromosome 6q14-15

• Published in: Experimental eye research Vol. 81; no. 4; pp. 401 - 406
• Main Authors: Singh, Krishna K., Ristau, Steven, Dawson, William W., Krawczak, Michael, Schmidtke, Jörg
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2005
• Subjects: ageing macular dystrophy; Animals; Chromosome Mapping - methods; Chromosomes, Human, Pair 6 - genetics; Disease Models, Animal; disease susceptibility; drusen; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Haplotypes; Humans; Macaca mulatta; Macular Degeneration - genetics; retina; Retinal Drusen - genetics; Macaca mulatta; disease susceptibility; retina; ageing macular dystrophy; drusen
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2005.02.011

Rhesus macaques (Macaca mulatta) are a natural model for retinal drusen formation. The present study aimed at clarifying whether chromosomal regions homologous to candidate genes for drusen formation and progression in humans are also associated with a drusen phenotype in rhesus macaques. Some 42 genetic markers from seven chromosomal regions implicated in macular degeneration syndromes in humans were tested for whether they identified homologous, polymorphic sequences in rhesus DNA. This was found to be the case for seven markers, all of which were subsequently screened for the presence of potentially disease-predisposing alleles in 52 randomly chosen adult animals from the Cayo Santiago population of rhesus macaques (Caribbean Primate Research Center, PR, USA). The high drusen prevalence expected in the Cayo Santiago colony was confirmed in our sample in that 38 animals were found to have drusen (73%). Logistic regression analysis revealed that some alleles of the rhesus homologue of anonymous human marker D6S1036 were consistently over-represented among affected animals. Of two candidate genes located in the respective region, allelic variation in one (IMPG1) showed strong association with drusen formation. We conclude that one or more genes located at the rhesus homologue of human 6q14-15 are likely to play a role in retinal drusen formation, a finding that represents a first step towards the identification of genetic factors implicated in macular drusen formation in rhesus macaques. This is an important tool for the separation of genetic and environmental factors which must occur before satisfactory management methods can be developed.