| Title: |
Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma |
| Authors: |
King, R; Struebing, FL; Li, Y; Wang, J; Koch, AA; Cooke Bailey, JN; Gharahkhani, P; MacGregor, S; Allingham, RR; Hauser, MA; Wiggs, JL; Geisert, EE; Allingham, R; Brilliant, M; Budenz, D; Fingert, J; Gaasterland, D; Gaasterland, T; Haines, JL; Hark, L; Igo, R; Kang, JH; Kraft, P; Lee, R; Lichter, P; Liu, Y; Moroi, S; Pasquale, LR; Realini, A; Rhee, D; Richards, JR; Ritch, R; Schuman, J; Scott, WK; Singh, K; Sit, A; Vollrath, D; Weinreb, RN; Wollstein, G; Zack, D; Aung, T; Burdon, KP; Cheng, CY; Craig, JE; Cree, AJ; Hammond, CJ; Hewitt, AW; Höhn, R; Hysi, P; Gonzalez, AII; Jonas, J; Khawaja, A; Khor, CC; Klaver, CCW; Pasutto, F; Mackey, D; Mitchell, P; Mishra, A; Pang, C; Springelkamp, H; Thorleifsson, G; Thorsteinsdottir, U; van Duijn, CM; Viswanathan, A; Vitart, V; Wojciechowski, R; Wong, T; Young, TL; Zeller, T |
| Contributors: |
Anderson, MG |
| Publisher Information: |
PUBLIC LIBRARY SCIENCE |
| Publication Year: |
2018 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60-100 days of age). The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to QTLs modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human POAG genome wide association study (NEIGHBORHOOD) to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10-6 for SNP rs76319873. POU6F2 is found in retinal ganglion cells ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1553-7390 |
| Relation: |
King, R., Struebing, F. L., Li, Y., Wang, J., Koch, A. A., Cooke Bailey, J. N., Gharahkhani, P., MacGregor, S., Allingham, R. R., Hauser, M. A., Wiggs, J. L., Geisert, E. E., Allingham, R., Brilliant, M., Budenz, D., Fingert, J., Gaasterland, D., Gaasterland, T., Haines, J. L. ,. Zeller, T. (2018). Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma. Plos Genetics, 14 (1), https://doi.org/10.1371/journal.pgen.1007145.; https://hdl.handle.net/11343/271116 |
| Availability: |
https://hdl.handle.net/11343/271116 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.9546427F |
| Database: |
BASE |