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RR Allingham, JL Wiggs, MA Hauser, KR LaRocque, B Broomer, FL Graham, EA del Bono, JR Shi, JL Haines, MA Pericak-Vance; Analysis of TJP1 (tight junction protein 1) as a Candidate Gene for POAG . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3380.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: TJP1, also known as ZO-1, is a gene that is located within a candidate region we identified on chromosome 15q for a subset of families with early-onset POAG (Allingham et. al., 2001). ZO-1 protein is expressed in tight junctions of cultured endothelial cells derived from Schlemms canal in the trabecular meshwork (Underwood JL et. al., Amer. J. Physio., 1999). Similar to myocilin, its expression is increased with glucocorticoid stimulation. We sequenced and analyzed the coding region of TJP1 from individuals with early-onset POAG for sequence variations. Methods: TJP1 sequence and intron/exon boundaries were determined by BLAT comparison between the TJP1 mRNA sequence (NM_003257) and the UC Santa Cruz genomic assembly (http://genomic.ucsc.edu/). Vector NTI (Informax, Bethesda, MD) was used to design primers flanking each exon. PCR reactions were optimized for each primer set and reaction products were purified. Sequencing reactions were run using either Beckman CEQ2000 or ABI3700 standard protocols. Products were cleaned using either Edge Biosystems Performa DTR Gel Filtration systems or Sephadex filtration columns. Sequences were aligned and analyzed using Sequencher (Gene Codes Co., Ann Arbor, MI). Results: Informed consent was obtained from all participating individuals. Genomic DNA samples obtained from 14 individuals affected with POAG from 11 unrelated families were analyzed. Each family had at least one member diagnosed with POAG by age 45. Sequences from each of the 29 exons of TJP1 were obtained. Sequences were run in both directions with the exception of exons 12, 13, and 25, which, due to technical reasons, were sequenced in one direction. A sequence variation in exon 24, Asp1335Ala was found in two of six affected individuals from family 5013, but did not segregate with disease status. A wobble polymorphism was identified in each of two additional families (His350His and Ala1364Ala). Conclusion: Variations in the coding region of TJP1 do not play an important role in the pathogenesis of POAG in this subset of early-onset families. This study, however, does not rule out the possibility that variations in the promoter region or untranslated regions of TJP1 may be important.
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