Pathogenicity analysis of missense mutations in MT-ND۶, a mitochondrial gene that encoded NADH dehydrogenase ۶

Backgrounds: Mitochondrial DNA (mtDNA), the circular genomes of microorganisms derivedfrom the early ancestors of modern eukaryotic cells. An mtDNA molecule could be a powerfultool for detection generations through the mother; therefore it is used to search for the ancestorsof many species over hundreds of generations. The mitochondrial genome encodes ۳۷ genes,including ۱۳ genes encoding proteins. Many of these genes encode the transmission chain.Related diseases with MT-ND۶, a mitochondrial genome that encodes NADH dehydrogenase ۶,include Encephalopathy, Leber, Lactic Acidosis, and Stroke-Like Episodes.Materials and Methods: We used the NCBI database to find missense and Pathogenic SNPsand then the physicochemical analysis was performed by protein structure prediction andannotation protein software.Results: In this study, we found ۶۳۹ missense mutations in MT-ND۶ that ۱۱ of ۶۳۹ mutationswere pathogenic. We explain the most important ones in the following.۱) In a first mutation converts a conserved Lue (۶۰), a hydrophobic AA into Ser, a hydrophilicAA. Our result showed that this mutation alters hydrophobicity in substituted position byEXPASY resource portal score: (-۰.۵۱۱), PROVEAN score: (-۵.۹۹), SIFT score: (۰.۰۰), and thePolyPhen database score: (۱.۰۰) is deleterious and probably damaging.۲) Tyr (۵۹), hydrophilic AA into Cys, a polar hydrophilic AA. EXPASY changing score is(۰.۴۲۲), PROVEAN score is (-۸.۸۵), SIFT score is (۰.۰۰) and PolyPhen with score (۱.۰۰) isdeleterious and probably damaging.Conclusion: Our results were predicted that it might conceivably be harmful, so MT-ND۶mutation was considered potentially pathologic. However, more investigations are essential.

کلیدواژه ها:

Mt-DNA ، MT-ND۶ ، Mitochondria ، Mutation ، Pathogen