Rhesus monkeys and humans share common susceptibility genes for age-related macular disease

Peter J. Francis, Binoy Appukuttan, Emily Simmons, Noelle Landauer, Jonathan Stoddard, Sara Hamon, Jurg Ott, Betsy Ferguson, Michael Klein, J. Timothy Stout, Martha Neuringer

Research output: Contribution to journalArticle

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Abstract

Age-related macular degeneration (AMD), a complex multigenic disorder and the most common cause of vision loss in the elderly, is associated with polymorphisms in the LOC387715/ARMS2 and HTRA1 genes on 10q26. Like humans, macaque monkeys possess a macula and develop age-related macular pathologies including drusen, the phenotypic hallmark of AMD. We genotyped a cohort of 137 unrelated rhesus macaques with and without macular drusen. As in humans, one variant within LOC387715/ARMS2 and one in HTRA1 were significantly associated with affected status. HTRA1 and the predicted LOC387715/ARMS2 gene were both transcribed in rhesus and human retina and retinal pigment epithelium. Among several primate species, orthologous exons for the human LOC387715/ARMS2 gene were present only in Old World monkeys and apes. In functional analyses, the disease-associated HTRA1 polymorphism resulted in a 2-fold increase in gene expression, supporting a role in pathogenesis. These results demonstrate that two genes associated with AMD in humans are also associated with macular disease in rhesus macaques and that one of these genes is specific to higher primates. This is the first evidence that humans and macaques share the same genetic susceptibility factors for a common complex disease.

Original languageEnglish (US)
Pages (from-to)2673-2680
Number of pages8
JournalHuman Molecular Genetics
Volume17
Issue number17
DOIs
StatePublished - 2008

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Macaca mulatta
Macular Degeneration
Genes
Macaca
Primates
Cercopithecidae
Retinal Pigment Epithelium
Hominidae
Genetic Predisposition to Disease
Haplorhini
Retina
Exons
Pathology
Gene Expression

ASJC Scopus subject areas

  • Genetics

Cite this

Francis, P. J., Appukuttan, B., Simmons, E., Landauer, N., Stoddard, J., Hamon, S., ... Neuringer, M. (2008). Rhesus monkeys and humans share common susceptibility genes for age-related macular disease. Human Molecular Genetics, 17(17), 2673-2680. https://doi.org/10.1093/hmg/ddn167

Rhesus monkeys and humans share common susceptibility genes for age-related macular disease. / Francis, Peter J.; Appukuttan, Binoy; Simmons, Emily; Landauer, Noelle; Stoddard, Jonathan; Hamon, Sara; Ott, Jurg; Ferguson, Betsy; Klein, Michael; Stout, J. Timothy; Neuringer, Martha.

In: Human Molecular Genetics, Vol. 17, No. 17, 2008, p. 2673-2680.

Research output: Contribution to journalArticle

Francis, PJ, Appukuttan, B, Simmons, E, Landauer, N, Stoddard, J, Hamon, S, Ott, J, Ferguson, B, Klein, M, Stout, JT & Neuringer, M 2008, 'Rhesus monkeys and humans share common susceptibility genes for age-related macular disease', Human Molecular Genetics, vol. 17, no. 17, pp. 2673-2680. https://doi.org/10.1093/hmg/ddn167
Francis PJ, Appukuttan B, Simmons E, Landauer N, Stoddard J, Hamon S et al. Rhesus monkeys and humans share common susceptibility genes for age-related macular disease. Human Molecular Genetics. 2008;17(17):2673-2680. https://doi.org/10.1093/hmg/ddn167
Francis, Peter J. ; Appukuttan, Binoy ; Simmons, Emily ; Landauer, Noelle ; Stoddard, Jonathan ; Hamon, Sara ; Ott, Jurg ; Ferguson, Betsy ; Klein, Michael ; Stout, J. Timothy ; Neuringer, Martha. / Rhesus monkeys and humans share common susceptibility genes for age-related macular disease. In: Human Molecular Genetics. 2008 ; Vol. 17, No. 17. pp. 2673-2680.
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