{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:11:04Z","timestamp":1793412664095,"version":"4.5.0"},"reference-count":29,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5300","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1997,1,31]]},"abstract":"<jats:p>\n            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 (\n            <jats:italic>GLC1A<\/jats:italic>\n            ) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (\n            <jats:italic>TIGR<\/jats:italic>\n            ) 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.\n          <\/jats:p>","DOI":"10.1126\/science.275.5300.668","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:35:26Z","timestamp":1027748126000},"page":"668-670","source":"Crossref","is-referenced-by-count":963,"title":["Identification of a Gene That Causes Primary Open Angle Glaucoma"],"prefix":"10.1126","volume":"275","author":[{"given":"Edwin M.","family":"Stone","sequence":"first","affiliation":[{"name":"E. 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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Fingert","sequence":"additional","affiliation":[{"name":"E. 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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wallace L. M.","family":"Alward","sequence":"additional","affiliation":[{"name":"E. 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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thai D.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"T. D. Nguyen and J. R. Polansky, Department of Ophthalmology, University of California, San Francisco, CA 94143-0730, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon R.","family":"Polansky","sequence":"additional","affiliation":[{"name":"T. D. Nguyen and J. R. Polansky, Department of Ophthalmology, University of California, San Francisco, CA 94143-0730, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara L. F.","family":"Sunden","sequence":"additional","affiliation":[{"name":"S. L. F. Sunden, D. Nishimura, A. Nystuen, V. C. Sheffield, Department of Pediatrics, University of Iowa College of Medicine, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl","family":"Nishimura","sequence":"additional","affiliation":[{"name":"S. L. F. Sunden, D. Nishimura, A. Nystuen, V. C. Sheffield, Department of Pediatrics, University of Iowa College of Medicine, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbot F.","family":"Clark","sequence":"additional","affiliation":[{"name":"A. F. Clark, Alcon Laboratories, Incorporated, Fort Worth, TX 76134, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Nystuen","sequence":"additional","affiliation":[{"name":"S. L. F. Sunden, D. Nishimura, A. Nystuen, V. C. Sheffield, Department of Pediatrics, University of Iowa College of Medicine, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Nichols","sequence":"additional","affiliation":[{"name":"E. 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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Mackey","sequence":"additional","affiliation":[{"name":"D. A. Mackey, Department of Ophthalmology, University of Melbourne, Melbourne 3002, Australia, and The Menzies Centre, University of Tasmania, Hobart, Tasmania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Ritch","sequence":"additional","affiliation":[{"name":"R. Ritch, Department of Ophthalmology, New York Eye and Ear Infirmary, New York, NY 10003, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Kalenak","sequence":"additional","affiliation":[{"name":"J. W. Kalenak, Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, WI 53226, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Randy","family":"Craven","sequence":"additional","affiliation":[{"name":"E. R. Craven, Department of Ophthalmology, University of Colorado School of Medicine, Denver, CO 80262, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val C.","family":"Sheffield","sequence":"additional","affiliation":[{"name":"S. L. F. Sunden, D. Nishimura, A. Nystuen, V. C. Sheffield, Department of Pediatrics, University of Iowa College of Medicine, Iowa City, IA 52242, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/0002-9394(75)90870-3","volume":"80","author":"Hiller R.","year":"1975","unstructured":"Hiller R., Kahn H. A., Am. J. Ophthalmol. 80, 62 (1975).","journal-title":"Am. J. Ophthalmol."},{"key":"e_1_3_1_3_2","first-page":"120","author":"Kahn H. A.","year":"1973","unstructured":"Kahn H. A., Moorhead H. B., U.S. Public Health Serv. Publ. NIH 73-4271973120.","journal-title":"U.S. Public Health Serv. Publ. NIH 73-427"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1001\/archopht.1990.01070040138048","volume":"108","author":"Tielsch J. M.","year":"1990","unstructured":"Tielsch J. M., et al., Arch. Ophthalmol. 108, 286 (1990).","journal-title":"Arch. Ophthalmol."},{"key":"e_1_3_1_5_2","first-page":"61","volume-title":"Transactions of the New Orleans Academy of Ophthalmology","author":"Tielsch J. M.","year":"1993","unstructured":"Tielsch J. M., Transactions of the New Orleans Academy of Ophthalmology, Ball S. F., Franklin R. M.KuglerAmsterdam19936168."},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S0161-6420(13)31615-7","volume":"100","author":"Johnson A. T.","year":"1993","unstructured":"Johnson A. T., et al., Ophthalmology 100, 524 (1993).","journal-title":"Ophthalmology"},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng0593-47","volume":"4","author":"Sheffield V. C.","year":"1993","unstructured":"Sheffield V. C., et al., Nature Genet. 4, 47 (1993).","journal-title":"Nature Genet."},{"key":"e_1_3_1_8_2","first-page":"62","volume":"54","author":"Richards J. E.","year":"1994","unstructured":"Richards J. E., et al., Am. J. Hum. Genet. 54, 62 (1994).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1006\/geno.1994.1269","volume":"21","author":"Wiggs J. L.","year":"1994","unstructured":"Wiggs J. L., et al., Genomics 21, 299 (1994).","journal-title":"Genomics"},{"key":"e_1_3_1_10_2","first-page":"1431","volume":"56","author":"Morissette J.","year":"1995","unstructured":"Morissette J., et al., Am. J. Hum. Genet. 56, 1431 (1995).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_1_11_2","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1101\/gr.6.9.862","volume":"6","author":"Sunden S. L. F.","year":"1996","unstructured":"Sunden S. L. F., et al., Genome Res. 6, 862 (1996).","journal-title":"Genome Res."},{"key":"e_1_3_1_12_2","unstructured":"Sheffield V. C. Stone E. M.unpublished data."},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1093\/hmg\/2.7.1084-a","volume":"2","author":"Watkins H. C.","year":"1993","unstructured":"Watkins H. C., et al., Hum. Mol. Genet. 2, 1084 (1993).","journal-title":"Hum. Mol. Genet."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/0888-7543(90)90286-4","volume":"8","author":"Lowe D. G.","year":"1990","unstructured":"Lowe D. G., et al., Genomics 8, 304 (1990).","journal-title":"Genomics"},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/365061a0","volume":"365","author":"Munro S.","year":"1993","unstructured":"Munro S., Thomas K. L., Abu-Shaar M., Nature 365, 61 (1993).","journal-title":"Nature"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2466335"},{"key":"e_1_3_1_17_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1084\/jem.170.1.123","volume":"170","author":"Tedder T. F.","year":"1989","unstructured":"Tedder T. F., et al., J. Exp. Med. 170, 123 (1989).","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_18_2","first-page":"1313","volume":"11","author":"Miura S.","year":"1991","unstructured":"Miura S., et al., Mol. Cell. Biol. 11, 1313 (1991).","journal-title":"Mol. Cell. Biol."},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1093\/intimm\/6.10.1567","volume":"6","author":"Takahashi T.","year":"1994","unstructured":"Takahashi T., et al., Int. Immunol. 6, 1567 (1994).","journal-title":"Int. Immunol."},{"key":"e_1_3_1_20_2","first-page":"113","volume":"12","author":"Polansky J. R.","year":"1989","unstructured":"Polansky J. R., et al., Prog. Clin. Biol. Res. 12, 113 (1989).","journal-title":"Prog. Clin. Biol. Res."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1093\/jb\/118.5.921","volume":"118","author":"Escribano J.","year":"1995","unstructured":"Escribano J., Ortego J., Coca-Prados M., J. Biochem. 118, 921 (1995).","journal-title":"J. Biochem."},{"key":"e_1_3_1_22_2","unstructured":"Nguyen T. D. Polansky J. R. Huang W.unpublished data; International patent application PCT\/US95\/14024 (1996)."},{"key":"e_1_3_1_23_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1101\/gr.5.2.136","volume":"5","author":"Lange K.","year":"1995","unstructured":"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)].","journal-title":"Genome Res."},{"key":"e_1_3_1_24_2","unstructured":"A 12.5-ng sample of each patient's DNA was used for the template in an 8.35-\u03bcl PCR mixture containing 1.25 \u03bcl of 10X buffer (100 mM tris-HCL pH 8.3 500 mM KCl 15 mM MgCl 2 ); the deoxynucleotides dCTP dATP dGTP and dTTP (300 \u03bcM for each); 1 pmol of each primer; and 0.25 units of Taq polymerase (Boehringer Mannheim). Samples were denatured for 5 min at 94\u00b0C and incubated for 35 cycles under the following conditions: 94\u00b0C for 30 s 55\u00b0C for 30 s and 72\u00b0C for 30 s in a DNA thermocycler (Omnigene). After amplification 5 \u03bcl of stop solution (95% formamide 10 mM NaOH 0.05% bromophenol blue 0.05% xylene cyanol) was added to each sample. Amplification products were denatured for 3 min at 94\u00b0C and electrophoresed on 6% polyacrylamide-5% glycerol gels at 25 W for about 3 hours. After electrophoresis gels were stained with silver nitrate (24)."},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/0003-2697(91)90120-I","volume":"196","author":"Bassam B. J.","year":"1991","unstructured":"Bassam B. J., Caetano-Anolles G., Gresshoff P. M., Anal. Biochem. 196, 80 (1991).","journal-title":"Anal. Biochem."},{"key":"e_1_3_1_26_2","unstructured":"PCR products were sequenced with fluorescent dideoxynucleotides on an Applied Biosystems (ABI) model 373 automated sequencer. All mutations were recognized by the approximately equal peak intensity of two fluorescent dyes at the mutant base. Mutations were confirmed by cloning the PCR product into pT7Blue T vector (Novagen Madison WI) and sequencing the cloned product with ABI fluorescent dye primer chemistry. Multiple clones were sequenced to confirm the presence of both mutant and normal clones. All sequencing was performed bidirectionally."},{"key":"e_1_3_1_27_2","first-page":"307","volume-title":"Basic Aspects of Glaucoma Research III","author":"Polansky J. R.","year":"1993","unstructured":"Polansky J. R., Basic Aspects of Glaucoma Research III, Lutjen-Drecoll E.SchattauerStuttgart, New York1993307318T. D. Nguyen et al., in ibid., pp. 331\u2013343."},{"key":"e_1_3_1_28_2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/0002-9394(79)90241-1","volume":"87","author":"Quigley H. A.","year":"1979","unstructured":"Quigley H. A., Maumenee A. E., Am. J. Ophthalmol. 87, 519 (1979);","journal-title":"Am. J. Ophthalmol."},{"key":"e_1_3_1_28_3","first-page":"51","volume":"111","author":"Mao L. K.","year":"1991","unstructured":"Mao L. K. , Stewart W. C. , Shields M. B., ibid. 111, 51 (1991).","journal-title":"ibid."},{"key":"e_1_3_1_29_2","unstructured":"This paper is dedicated to the memory of Frederick C. Blodi M.D. (1917\u20131996). 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."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.275.5300.668","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T23:04:41Z","timestamp":1705100681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.275.5300.668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,1,31]]},"references-count":29,"journal-issue":{"issue":"5300","published-print":{"date-parts":[[1997,1,31]]}},"alternative-id":["10.1126\/science.275.5300.668"],"URL":"https:\/\/doi.org\/10.1126\/science.275.5300.668","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,1,31]]}}}