In-silico analysis of pathogenic SNPs in JAG۱ gene

Backgrounds: The Notch signaling pathway is an important participator in the development andhomeostasis of the cardiovascular system. Mutations in Notch receptors and ligands have beenidentified that impact both the heart and the vasculature. Mutations in the gene encoding thehuman Notch ligand jagged ۱ result in a pleiotropic disorder called Alagille syndrome. Cardiacdefects are seen in more than ۹۵% of AGS patients. To identify the structural and functionaleffects of mutations, various powerful bioinformatics tools are available. The aim of this study isthe identification of high-risk non-synonymous single nucleotide variants in the JAG۱ gene viabioinformatics tools.Materials and Methods: SNPs for the JAG۱ gene were collected from a web-based data sourcesuch as NCBI/dbSNP database. Among the identified polymorphisms in this gene, ۸۶۰ missensevariants are retrieved. Deleterious single-nucleotide polymorphisms (SNPs) were screened usingthe bioinformatics tools such as SIFT, Pplyphen-۲, PHD-SNP, PROVEAN, PANTHER andPMut servers.Results: We found ۸۶۰ missense mutations in JAG۱ Gene and ۱۶ of ۸۶۰ mutations werepathogenic. The results obtained from the set of bioinformatics tools identify ۸ high-riskmutations in the JAG۱ gene.Conclusion: Collectively, eight mutations including G۲۷۴D, R۱۸۴C, L۳۷S, C۶۹۳T, C۷۸S,C۷۸Y, C۷۸G and C۷۸R for further studies were identified. A Better understanding of relateddiseases caused by mutations in the JAG۱ gene was achieved using in-silico prediction. All ofthese mutations organized possible candidates for further genetic studies.