Wiggs, J. L., Howell, G. R., Linkroum, K., Abdrabou, W., Hodges, E., Braine, C. E., Pasquale, L. R., Hannon, G. J., Haines, J. L., John, S. W. M. (April 2013) Variations in COL15A1 and COL18A1 influence age of onset of primary open angle glaucoma. Clinical Genetics, 84 (2). p. 167. ISSN 00099163
Abstract
Primary open angle glaucoma (POAG) is a genetically and phenotypically complex disease that is a leading cause of blindness worldwide. Previously we completed a genome-wide scan for early-onset POAG that identified a locus on 9q22 (GLC1J). To identify potential causative variants underlying GLC1J, we used targeted DNA capture followed by high throughput sequencing of individuals from four GLC1J pedigrees, followed by Sanger sequencing to screen candidate variants in additional pedigrees. A mutation likely to cause early-onset glaucoma was not identified, however COL15A1 variants were found in the youngest affected members of 7 of 15 pedigrees with variable disease onset. In addition, the most common COL15A1 variant, R163H, influenced the age of onset in adult POAG cases. RNA in situ hybridization of mouse eyes shows that Col15a1 is expressed in the multiple ocular structures including ciliary body, astrocytes of the optic nerve and cells in the ganglion cell layer. Sanger sequencing of COL18A1, a related multiplexin collagen, identified a rare variant, A1381T, in members of three additional pedigrees with early-onset disease. These results suggest genetic variation in COL15A1 and COL18A1 can modify the age of onset of both early and late onset POAG.
| Item Type: | Paper |
|---|---|
| Subjects: | Investigative techniques and equipment Investigative techniques and equipment > assays Investigative techniques and equipment > assays > next generation sequencing |
| CSHL Authors: | |
| Communities: | CSHL labs > Hannon lab |
| Depositing User: | Matt Covey |
| Date: | 26 April 2013 |
| Date Deposited: | 24 Jun 2013 19:32 |
| Last Modified: | 17 Sep 2013 19:11 |
| PMCID: | PMC3771394 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/28374 |
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