Rhesus monkeys and humans share common susceptibility genes for age-related macular disease.
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.
Casey Eye Institute, Oregon Health and Science University, Portland, OR 97239, USA. francisp@ohsu.edu
Peter J
PJ
Francis
Binoy
B
Appukuttan
Emily
E
Simmons
Noelle
N
Landauer
Jonathan
J
Stoddard
Sara
S
Hamon
Jurg
J
Ott
Betsy
B
Ferguson
Michael
M
Klein
J Timothy
JT
Stout
Martha
M
Neuringer
D000375:Aging; D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008253:Macaca mulatta; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000235:genetics*
C514392:ARMS2 protein, human; D011506:Proteins; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases