Identification of a Gene That Causes Primary Open Angle Glaucoma

American Association for the Advancement of Science (AAAS) - Tập 275 Số 5300 - Trang 668-670 - 1997
Edwin M. Stone1, John H. Fingert1, Wallace L.M. Alward1, Thai Nguyen2, Jon R. Polansky2, Sara L.F. Sunden3, Darryl Nishimura3, Abbot F. Clark4, Arne Nystuen3, Brian E. Nichols1, David A. Mackey5, Robert Ritch6, Jeffrey W. Kalenak7, E. Randy Craven8, Val C. Sheffield3
1E. M. Stone, J. H. Fingert, W. L. M. Alward, B. E. Nichols, Department of Ophthalmology, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
2T. D. Nguyen and J. R. Polansky, Department of Ophthalmology, University of California, San Francisco, CA 94143-0730, USA.
3S. L. F. Sunden, D. Nishimura, A. Nystuen, V. C. Sheffield, Department of Pediatrics, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
4A. F. Clark, Alcon Laboratories, Incorporated, Fort Worth, TX 76134, USA.
5D. A. Mackey, Department of Ophthalmology, University of Melbourne, Melbourne 3002, Australia, and The Menzies Centre, University of Tasmania, Hobart, Tasmania.
6R. Ritch, Department of Ophthalmology, New York Eye and Ear Infirmary, New York, NY 10003, USA.
7J. W. Kalenak, Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
8E. R. Craven, Department of Ophthalmology, University of Colorado School of Medicine, Denver, CO 80262, USA.

Tóm tắt

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma ( GLC1A ) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein ( TIGR ) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.

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Tài liệu tham khảo

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YAC-STS content analysis was performed by PCR amplification of each STS from DNA prepared from individual YAC clones. PCR products were electrophoresed on 2% agarose gels and stained with ethidium bromide. The presence or absence of amplification was scored and this data used to deduce the minimum tiling path of the chromosome 1q glaucoma interval. Radiation hybrid mapping was performed with the Genebridge 4 radiation hybrid panel available from Research Genetics. DNA from each radiation hybrid clone was amplified in duplicate with STS primers. PCR products were electrophoresed on 2% agarose gels and visualized with ethidium bromide. The gels were scored for the presence of amplified product. Radiation hybrid maps based on this data were constructed with the computer programs RH2PT, RHMAXLIK, and RHMINBRK [ Lange K. , Boehnke M. , Cox D. R. , Lunetta K. L., Genome Res. 5, 136 (1995)].

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This paper is dedicated to the memory of Frederick C. Blodi M.D. (1917–1996). We thank G. Beck N. Butler D. Crouch R. Hockey T. Love T. Rohklina L. Streb C. Taylor C. Wiles and K. Vandenburgh for their technical assistance. Supported in part by the Carver Charitable Trust NIH grants EY10564 EY08905 EY02477 and EY02162 and an unrestricted grant from Research to Prevent Blindness New York NY.