In-silico analysis of SNPs in mitochondrial MT-ND۴ gene

Backgrounds: MT-ND۴ is a mitochondrial gene encoding a subunit of the mitochondrialcomplex I. LHON is a maternally inherited disease and Mitochondrial DNA replacementmutation in this disease was identified. To identify the structural and functional effects ofmutations, various powerful bioinformatics tools are available. The aim of this study is theidentification of high-risk non-synonymous single nucleotide variants in the MT-ND۴ gene viabioinformatics tools.Materials and Methods: SNPs for the MT-ND۴ gene were collected from a web-based datasource such as NCBI/dbSNP database. Among the identified polymorphisms in this gene, ۸۲۱missense variants are retrieved. Then, the pathogenicity of missense variants are consideredusing different bioinformatics tools. The stability of these mutant proteins, conservation of aminoacids structural changes are analyzed by bioinformatics tools. After the identification of high-riskmutations, the changes in the hydrophobicity of high-risk amino acid substitutions areconsidered.Results: We found ۸۲۱ missense mutations in MT-ND۴ that ۳۲ of ۸۲۱ mutations werepathogenic. Deleterious single nucleotide polymorphisms (SNPs) were screened using thebioinformatics tools such as SIFT, Polyphen, PHD-SNP, PROVEAN and SNP&GO. The resultsobtained from the set of bioinformatics tools identify high-risk mutations in the MT-ND۴ gene.Conclusion: Collectively, six mutations including R۳۴۰S/G, R۳۴۰H, T۱۰۹A, I۱۶۵T and V۳۱۳Ifor further studies were identified. A Better understanding of related diseases caused bymutations in the MT-ND۴ gene was achieved using In-silico prediction. All of these mutationsconstitute possible candidates for further genetic studies.