In silico Analysis of Single Nucleotide Polymorphisms (SNPS) in Human Factor VIII GeneDownload PDF
F8 gene is extremely large (186 kb) and consists of 26 exons. F8 is located on the long arm of the Xq28 region of the X chromosome. Mutations in this gene can occur at diverse sites in a variety of types, such as structural variation and sequence variation. Single Nucleotide Polymorphisms (SNPs) are the most abundant sequence variations encountered in a genome playing a major role in understanding of the genetic basis of many complex human diseases, the nonsynonymous SNPs (nsSNPs) are known to be deleterious or disease-causing variations because they alter protein sequence, structure, and function. F8 gene plays a major role in hemophilia A. A computational-based (In Silico) analysis has been done to evaluate the phenotypic effect of nsSNPs in human Out of total of 6021 SNPs in the F8 gene, 1276 were nsSNPs, 626 were missenes mutation and 650 duo to nonsense mutation, 54 occurred in the 3’utr and 24 occurred in 5’utr Among the predicted nsSNPs, (rs371422922), (rs370369511), (rs1800288), (rs368808810) and (rs373079141), were identified as deleterious and highly damaging by the SIFT and PolyPhen programs. The protein structural analysis of these amino acid variants was performed using (I mutant and PHD), where Modeling of these amino acid substitutions prepared by Project hope. From a comparison of the stabilizing residues of the native and mutant proteins, we propose that these variants could be an important candidate for hemophilia A, caused by the F8 gene and other pathological condition.
Keywords: Single Nucleotide Polymorphisms (SNPs), F8 gene, In silico analysis, nonsynonymous SNPs (nsSNPs), 3’utr, 5’utr, Polyphen and SIFT, hemophilia A (HA)