In silico analysis for determining the deleterious nonsynonymous single nucleotide polymorphisms of genes.

TitleIn silico analysis for determining the deleterious nonsynonymous single nucleotide polymorphisms of genes.
Publication TypeJournal Article
Year of Publication2019
AuthorsYadegari F, Majidzadeh K
JournalMol Biol Res Commun
Volume8
Issue4
Pagination141-150
Date Published2019 Dec
ISSN2345-2005
Abstract

Recent advances in DNA sequencing techniques have led to an increase in the identification of single nucleotide polymorphisms (SNPs) in and genes, but no further information regarding the deleterious probability of many of them is available (Variants of Unknown Significance/VUS). As a result, in the current study, different sequence- and structure-based computational tools including SIFT, PolyPhen2, PANTHER, SNPs&GO, FATHMM, SNAP, PhD-SNP, Align-GVGD, and I-Mutant were utilized for determining how resulted BRCA protein is affected by corresponding missense mutations. FoldX was used to estimate mutational effects on the structural of BRCA proteins. Variants were considered extremely deleterious only when all tools predicted them to be deleterious. A total of 10 VUSs in (Cys39Ser, Cys64Gly, Phe861Cys, Arg1699Pro, Trp1718Cys, Phe1761Ser, Gly1788Asp, Val1804Gly, Trp1837Gly, and Trp1837Cys) and 12 in (Leu2510Pro, Asp2611Gly, Tyr2660Asp, Leu2686Pro, Leu2688Pro, Tyr2726Cys, Leu2792Pro, Gly2812Glu, Gly2813Glu, Arg2842Cys, Asp3073Gly, and Gly3076Val) were considered as extremely deleterious. Results suggested that deleterious N- and C-terminal domain of the and C-terminus. Utilizing evolutionary conservation analysis, we demonstrated that the majority of deleterious SNPs ensue in highly conserved regions of genes. Furthermore, utilizing FoldX, we demonstrated that alterations in the function of proteins are not always together with stability alterations.

DOI10.22099/mbrc.2019.34198.1420
Alternate JournalMol Biol Res Commun
PubMed ID32042831
PubMed Central IDPMC6995337