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XiangDi Wang, Steven Hart, Janey Wiggs, Eldon Geisert, ; Mouse Genomic Loci Modulating Corneal Thickness. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6230.
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© ARVO (1962-2015); The Authors (2016-present)
One of the risk factors for developing glaucoma is central corneal thickness (CCT). We have used a mouse genetic reference panel (the BXD RI strain set) to define mammalian genomic loci modulating CCT.
CCT was measured in 50 BXD RI strains between 60-90 days of age. The mice were deeply anesthetized and the eyes were positioned in front of the Mouse Bore of a Bioptigen ocular contrast tomography (OCT) system. The cornea was put into the appropriate focal plane and scanned. The corneal scans were then saved to a portable hard drive for subsequent analysis. The central corneal thickness was measured three times for each eye using the Mouse Retina Program, In Vivo Vue Clinic, in the Bioptigen Software. CCT data for each strain was averaged and used to identify quantitative trait loci (QTLs) modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org).
This analysis revealed one significant QTL on Chr 13 and several suggestive QTLs on Chr 1, Chr 7, Chr 11 and Chr 16. The significant locus on Chr 13 was examined further to define potential candidate genes modulating this eye phenotype. Using the eye microarray dataset (HEIMED) on GeneNetwork, we identified cis-QTLs that could be modulating CCT in the BXD RI strain set. There were 11 genes that are cis-QTLs in this region of Chr 13: Lyst, Hecw1, Cdc2l5, Rala, Vps41, Stard3nl, Sfrp4, Trim27, Zkscan3, Hist1h4b and Hist1h4i. Of these 11 genes only three appeared to be expressed in our cornea array dataset: Lyst (lysosomal trafficking regulator), Rala (v-ral simian leukemia viral oncogene homolog) and Trim27 (tripartite motif-containing 27). These candidate genes were examined to determine if they are potential risk factors for human glaucoma. LYST was found to have a significant p value (p = 0.0084) in relationship to all human glaucoma cases in the results of the NEIGHBOR/GLAUGEN meta-analysis when Bonferroni corrected for the three tests.
This novel approach has identified a putative gene modulating CCT in the mouse and a potential risk factor for primary open angle glaucoma.
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