Abstract
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 1.80Å and 1.54Å. Hence, we conclude based on our study that the above mutations could be the major target mutations in causing the glutathione synthetase deficiency.
Highlights
The simplest form of genetic variations is the substitution of one nucleotide for another, termed Single Nucleotide Polymorphism or SNPs
We identified the possible mutations with the help of Sorting Intolerant From Tolerant (SIFT) and PolyPhen programs, proposed a modeled structure for mutant proteins and checked for structural stability
Inborn errors of metabolism include a wide range of defects of various gene products that affect intermediary metabolism in the body
Summary
The simplest form of genetic variations is the substitution of one nucleotide for another, termed Single Nucleotide Polymorphism or SNPs. The simplest form of genetic variations is the substitution of one nucleotide for another, termed Single Nucleotide Polymorphism or SNPs They are randomly distributed throughout our genome that make each of us genetically unique and plays a direct or indirect role in phenotypic expression [1,2,3]. They contribute to family resemblance with regard to external features and to the risk of developing certain disorders. It is expected that some more frequent missense mutations arising from SNPs in the coding regions will be associated with common genetic disorders [7]
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