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Human Molecular Genetics Advance Access published online on June 4, 2008
Human Molecular Genetics, doi:10.1093/hmg/ddn167
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Rhesus Monkeys and Humans Share Common Susceptibility Genes for Age-Related Macular Disease

Peter J. Francis1,§,*, Binoy Appukuttan1,§, Emily Simmons1, Noelle Landauer2, Jonathan Stoddard1, Sara Hamon3, Jurg Ott3,4, Betsy Ferguson2, Michael Klein1, J. Timothy Stout1 and Martha Neuringer2

1 Casey Eye Institute, Oregon Health & Science University, Portland, OR. 2 Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR. 3 Laboratory of Statistical Genetics, Rockefeller University, New York, NY 4 Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China

* Corresponding author: Peter J Francis Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Blvd Portland, OR. 97239 Tel: 503 418 1627 Fax: 503 494 7233 Email: francisp{at}ohsu.edu

Received March 21, 2008; Revised May 27, 2008; Accepted June 3, 2008

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.

§ these individuals contributed equally to this article.


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