Glaucoma is a leading cause of blindness world-wide and the second leading cause of blindness in the United States. About 80,000 of the 2,000,000 affected Americans are blind from glaucoma, and African Americans are at increased risk of developing the disease. It is estimated that as many as 50% of affected individuals do not realize that they have glaucoma. For many individuals, irreversible damage will have occurred by the time diagnosis and treatment have begun. Because treatments exist which can slow or stop progression of the disease, presymptomatic testing could potentially save sight in many individuals. Because the existing treatments don't work for everyone, improved treatment approaches are also needed. The PI long range goal is to identify genes responsible for adult onset forms of primary open angle glaucoma and to use cloned copies of those genes as tools with which to explore the underlying mechanisms of the disease, develop presymptomatic test(s), and design novel approaches to therapy and prevention. The approach of this project is to identify the location of glaucoma gene(s) on human chromosomes and to do mutation screening of candidate genes located at the site of mapped glaucoma genes. An initial collection of 56 families will be expanded, and sib pairs and isolate individuals will also be recruited. A genome scan will be carried out by screening DNA from family members with microsatellite repeat genetic markers from throughout the genome. Fine-scale mapping will be carried out in the immediate vicinity of the known glaucoma genes. Genes that have already been mapped to the region for which linage was detected will be evaluated for the presence of mutations in affected family members. Several specific candidate genes have been selected for use in mutation screening. Identification of new glaucoma genes will enhance our understanding of disease processes and assist in development of new diagnostic tests and alternative therapies.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY011671-02
Application #
2838375
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1997-12-01
Project End
2002-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Bailey, Jessica N Cooke; Gharahkhani, Puya; Kang, Jae H et al. (2018) Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. Invest Ophthalmol Vis Sci 59:629-636
Khawaja, Anthony P; Cooke Bailey, Jessica N; Wareham, Nicholas J et al. (2018) Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. Nat Genet 50:778-782
Pasquale, Louis R (2016) Vascular and autonomic dysregulation in primary open-angle glaucoma. Curr Opin Ophthalmol 27:94-101
Li, Zheng; Allingham, R Rand; Nakano, Masakazu et al. (2015) A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet 24:3880-92
Kang, J H; Loomis, S J; Yaspan, B L et al. (2014) Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. Eye (Lond) 28:662-71
Springelkamp, Henriët; Höhn, René; Mishra, Aniket et al. (2014) Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun 5:4883
Loomis, Stephanie J; Kang, Jae H; Weinreb, Robert N et al. (2014) Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss. Ophthalmology 121:508-16
Garnai, Sarah J; Huyghe, Jeroen R; Reed, David M et al. (2014) Congenital cataracts: de novo gene conversion event in CRYBB2. Mol Vis 20:1579-93
Liu, Yutao; Garrett, Melanie E; Yaspan, Brian L et al. (2014) DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma. Invest Ophthalmol Vis Sci 55:8251-8
Bailey, Jessica N Cooke; Yaspan, Brian L; Pasquale, Louis R et al. (2014) Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma. Hum Genet 133:1319-30

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