Sabika Firasat1, Haiba Kaul2, Usman Ali Ashfaq3, Sobia Idrees3,4. 1. Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. 2. Genetics Division, Department of Livestock Production, University of Veterinary and Animal Sciences, Ravi Campus, Pattoki, Pakistan. haibakaul@gmail.com. 3. Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan. 4. School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Kensington, Sydney, Australia.
Abstract
PURPOSE: The purpose of this study was to characterize the five missense mutations in CYP1B1 gene identified in Pakistani families affected with primary congenital glaucoma (PCG) using various bioinformatics and protein modeling tools. METHODS: We previously reported four novel missense mutations in CYP1B1 gene segregating in consanguineous Pakistani families. These mutations were identified by direct sequencing of all coding exons, the exon-intron boundaries and the 5' untranslated region of CYP1B1 using genomic DNA from affected and unaffected family members. In order to understand the effect of CYP1B1 mutations on protein structure and function, we used bioinformatics tools to investigate five mutations including four novels (W434R, D374E, L487P and L177R) and one known (E229K) mutation previously reported by our group in four Pakistani PCG-affected families. RESULTS: In silico analysis of the missense mutations using the computational algorithms SNAP, I-Mutant 2.0 IUPred, PrDOS and PASTA predicted pathogenic effects on stability and function of protein. CONCLUSION: In silico analysis of identified mutations confirmed their molecular pathogenicity. Similar analysis will be helpful in understanding of the biological role of CYP1B1 and the effect of mutations on the regulatory and enzymatic functions of CYP1B1 that result in PCG.
PURPOSE: The purpose of this study was to characterize the five missense mutations in CYP1B1 gene identified in Pakistani families affected with primary congenital glaucoma (PCG) using various bioinformatics and protein modeling tools. METHODS: We previously reported four novel missense mutations in CYP1B1 gene segregating in consanguineous Pakistani families. These mutations were identified by direct sequencing of all coding exons, the exon-intron boundaries and the 5' untranslated region of CYP1B1 using genomic DNA from affected and unaffected family members. In order to understand the effect of CYP1B1 mutations on protein structure and function, we used bioinformatics tools to investigate five mutations including four novels (W434R, D374E, L487P and L177R) and one known (E229K) mutation previously reported by our group in four Pakistani PCG-affected families. RESULTS: In silico analysis of the missense mutations using the computational algorithms SNAP, I-Mutant 2.0 IUPred, PrDOS and PASTA predicted pathogenic effects on stability and function of protein. CONCLUSION: In silico analysis of identified mutations confirmed their molecular pathogenicity. Similar analysis will be helpful in understanding of the biological role of CYP1B1 and the effect of mutations on the regulatory and enzymatic functions of CYP1B1 that result in PCG.
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