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Human Molecular Genetics Advance Access originally published online on May 10, 2008
Human Molecular Genetics 2008 17(16):2474-2485; doi:10.1093/hmg/ddn147
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The Primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress–response pathway

Jonathan M. Skarie and Brian A. Link*

Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA

* To whom correspondence should be addressed at: Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road BSB 405, Milwaukee, WI 53226, USA. Tel: +1 4144568072; Fax: +1 4144566517; Email: blink{at}mcw.edu

Received February 25, 2008; Accepted May 7, 2008

Primary open-angle glaucoma (POAG) is a genetically complex neuropathy that affects retinal ganglion cells and is a leading cause of blindness worldwide. WDR36, a gene of unknown function, was recently identified as causative for POAG at locus GLC1G. Subsequent studies found disease-associated variants in control populations, leaving the role of WDR36 in this disease unclear. To address this issue, we determined the function of WDR36. We studied Wdr36 in zebrafish and found it is the functional homolog of yeast Utp21. Utp21 is cell essential and functions in the nucleolar processing of 18S rRNA, which is required for ribosome biogenesis. Evidence for functional homology comes from sequence alignment, ubiquitous expression, sub-cellular localization to the nucleolus and loss-of-function phenotypes that include defects in 18S rRNA processing and abnormal nucleolar morphology. Additionally, we show that loss of Wdr36 function leads to an activation of the p53 stress–response pathway, suggesting that co-inheritance of defects in p53 pathway genes may influence the impact of WDR36 variants on POAG. Although these results overall do not provide evidence for or against a role of WDR36 in POAG, they do provide important baseline information for future studies.


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T. K. Footz, J. L. Johnson, S. Dubois, N. Boivin, V. Raymond, and M. A. Walter
Glaucoma-associated WDR36 variants encode functional defects in a yeast model system
Hum. Mol. Genet., April 1, 2009; 18(7): 1276 - 1287.
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