In silico analysis predicting effects of deleterious SNPs of human ETV۶ gene on its functions

Backgrounds: An ETS transcription factor is encoded by ETV۶. An N-terminal pointed (PNT)domain that is involved in protein-protein interactions with itself and other proteins, as well as aC-terminal DNA-binding domain, make up the product of this gene. It appears to be essentialfor hematopoiesis and the preservation of the growing vascular network, according tomouse knockout experiments. This gene has been connected to chromosomal rearrangementsassociated with leukemia and congenital fibrosarcoma. A familial thrombocytopeniaand leukemia propensity condition is caused by germ line mutations in ETV۶.Thrombocytopenia is usually mild and almost entirely penetrant. Leukemia is reported in ∼۳۰%of carriers and is most often B-cell acute lymphoblastic leukemia. In this study, ۵ singlenucleotide polymorphism (SNP) are checked which are identified as missense change in theNational center for biotechnology information (NCBI) on the SNP database.Materials and Methods: In NCBI/SNP database ۵,۳۸۹ SNPs were found for ETV۶. Missensevariant and pathogenic filters were applied and the result shows ۵ SNP (rs۷۲۴۱۵۹۹۴۷ P>L,rs۷۸۶۲۰۵۱۵۵ L>P, rs۷۲۴۱۵۹۹۴۶ R>L, rs۷۲۴۱۵۹۹۴۵ R>S, rs۷۸۶۲۰۵۲۲۶ R>G). Their effect on thefinal protein product was checked.Results: The results of this research with bioinformatical tools (SIFT, PolyPhen-۲, PROVEAN,SNP&GO, Phdsnp) shows that Reference SNP for instance (rs) ۷۸۶۲۰۵۱۵۵ causes change L(Leu) to P (Pro) in ۳۴۹rd amino acid residue in ETV۶ transcript, can produce an abnormalprotein that can have an inappropriate effect on patients with this polymorphism.Conclusion: Based on the results were obtained these SNPs most probably deleterious and onlyrs۷۲۴۱۵۹۹۴۷ in the PROVEAN and SNP & GO databases were declared neutral.

کلیدواژه ها:

ETV۶ ، SNP ، Bioinformatics