It is becoming more and more apparent that most genetic disorders are caused by biochemical abnormalities. Recent advances in human genome project and related research have showed us to detect and understand most of t...It is becoming more and more apparent that most genetic disorders are caused by biochemical abnormalities. Recent advances in human genome project and related research have showed us to detect and understand most of the inborn errors of metabolism. These are often caused by point mutations manifested as single-nucleotide-polymorphisms (SNPs). The GSS gene inquested in this work was analyzed for potential mutations with the help of computational tools like SIFT, PolyPhen and UTRscan. It was noted that 84.38% nsSNPs were found to be deleterious by the sequence homology based tool (SIFT), 78.13% by the structure homology based tool (PolyPhen) and 75% by both the SIFT and PolyPhen servers. Two major mutations occurred in the native protein (2HGS) coded by GSS gene at positions R125C and R236Q. Then a modeled structure for the mutant proteins (R125C and R236Q) was proposed and compared with that of the native protein. It was found that the total energy of the mutant (R125C and R236Q) proteins were -31893.846 and -31833.818 Kcal/mol respectively and that of the native protein was -31977.365 Kcal/mol. Also the RMSD values between the native and mutant (R125C and R236Q) type proteins were 1.80? and 1.54?. Hence, we conclude based on our study that the above mutations could be the major target mutations in causing the glutathione synthetase deficiency.展开更多
In this work, we have analyzed the genetic variation that can alter the expression and the function in BRCA2 gene using computational methods. Out of the total 534 SNPs, 101 were found to be non synonymous (nsSNPs). A...In this work, we have analyzed the genetic variation that can alter the expression and the function in BRCA2 gene using computational methods. Out of the total 534 SNPs, 101 were found to be non synonymous (nsSNPs). Among the 7 SNPs in the untranslated region, 3 SNPs were found in 5′ and 4 SNPs were found in 3′ un-translated regions (UTR). Of the nsSNPs 20.7% were found to be damaging by both SIFT and PolyPhen server among the 101 nsSNPs investigated. UTR resource tool suggested that 2 SNPs in the 5′ UTR region and 4 SNPs in the 3′ UTR regions might change the protein expression levels. The mutation from asparagine to isoleucine at the position 3124 of the native protein of BRCA2 gene was most deleterious by both SIFT and PolyPhen servers. A structural analysis of this mutated protein and the native protein was made which had an RMSD value of 0.301 nm. Based on this work, we proposed that this most deleterious nsSNP with an SNPid rs28897759 is an important candidate for the cause of breast cancer by BRCA2 gene.展开更多
文摘It is becoming more and more apparent that most genetic disorders are caused by biochemical abnormalities. Recent advances in human genome project and related research have showed us to detect and understand most of the inborn errors of metabolism. These are often caused by point mutations manifested as single-nucleotide-polymorphisms (SNPs). The GSS gene inquested in this work was analyzed for potential mutations with the help of computational tools like SIFT, PolyPhen and UTRscan. It was noted that 84.38% nsSNPs were found to be deleterious by the sequence homology based tool (SIFT), 78.13% by the structure homology based tool (PolyPhen) and 75% by both the SIFT and PolyPhen servers. Two major mutations occurred in the native protein (2HGS) coded by GSS gene at positions R125C and R236Q. Then a modeled structure for the mutant proteins (R125C and R236Q) was proposed and compared with that of the native protein. It was found that the total energy of the mutant (R125C and R236Q) proteins were -31893.846 and -31833.818 Kcal/mol respectively and that of the native protein was -31977.365 Kcal/mol. Also the RMSD values between the native and mutant (R125C and R236Q) type proteins were 1.80? and 1.54?. Hence, we conclude based on our study that the above mutations could be the major target mutations in causing the glutathione synthetase deficiency.
文摘In this work, we have analyzed the genetic variation that can alter the expression and the function in BRCA2 gene using computational methods. Out of the total 534 SNPs, 101 were found to be non synonymous (nsSNPs). Among the 7 SNPs in the untranslated region, 3 SNPs were found in 5′ and 4 SNPs were found in 3′ un-translated regions (UTR). Of the nsSNPs 20.7% were found to be damaging by both SIFT and PolyPhen server among the 101 nsSNPs investigated. UTR resource tool suggested that 2 SNPs in the 5′ UTR region and 4 SNPs in the 3′ UTR regions might change the protein expression levels. The mutation from asparagine to isoleucine at the position 3124 of the native protein of BRCA2 gene was most deleterious by both SIFT and PolyPhen servers. A structural analysis of this mutated protein and the native protein was made which had an RMSD value of 0.301 nm. Based on this work, we proposed that this most deleterious nsSNP with an SNPid rs28897759 is an important candidate for the cause of breast cancer by BRCA2 gene.
