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Abstract #28121 Published in IGR 13-1
Polymorphisms in an intronic region of the myocilin gene associated with primary open-angle glaucoma-a possible role for alternate splicing
Eswari Pandaranayaka PJ; Prasanthi N; Kannabiran N; Rangachari K; Dhivya M; Krishnadas SR; Sundaresan P; Krishnaswamy SMolecular Vision 2010; 16: 2891-2902
Purpose: To examine the possible role of alternate splicing leading to aggregation of myocilin in primary open-angle glaucoma. Methods: Several single nucleotide variations found in the myocilin (MYOC) genomic region were collected and examined for their possible role in causing splice-site alterations. A model for myocilin built using a knowledge-based consensus method was used to map the altered protein products. A total of 150 open-angle glaucoma patients and 50 normal age-matched control subjects were screened for the predicted polymorphisms, and clustering was performed. Results: A total of 124 genomic variations were screened, and six polymorphisms that lead to altered protein products were detected as possible candidates for the alternative splicing mechanism. Five of these lay in the intronic regions, and the one that lay in the exon region corresponded to the previously identified polymorphism (Tyr347Tyr) implicated in primary open-angle glaucoma. Experimentally screening the intronic region of the MYOC gene showed the presence of the predicted g.14072G>A polymorphism, g.1293C/T heterozygous polymorphism, instead of our predicted g.1293C/- polymorphism. Other than the prediction, two novel SNPs (g.1295G>T and g.1299T>G) and two reported SNPs (g. 1284G>T and g.1286G>T) were also identified. Cluster analysis showed the g.14072G>A homozygous condition was more common in this cohort than the heterozygous condition. Conclusions: We previously proposed that the disruption of dimer or oligomer formation by the C-term region allows greater chances of nucleation for aggregation. Here we suggest that polymorphisms in the myocilin genomic region that cause synonymous codon changes or those that occur in the intron regions can possibly lead to altered myocilin protein products through altered intron-exon splicing.
S. Krishnaswamy. Centre of Excellence in Bioinformatics, School of Biotechnology, Madurai Kamaraj University, Madurai - 625021, Tamilnadu, India. krishna@mrna.tn.nic.in
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
