Benign and conserved DNA variants m.8860A>G and m.8701A>G indicating mitochondrial genetic drift in Pakistani population

Abstract

Background: Mitochondria are vital subcellular organelles that orchestrate the intricate process of oxidative phosphorylation (OXPHOS), generating adenosine triphosphate (ATP) as the primary energy molecule fueling cellular activities. During our research on mitochondrial mutations in breast cancer patients, we identified two notable single nucleotide polymorphisms (SNPs) present in both cancer patients and control individuals from the Pakistani population. Materials and methods: DNA was extracted from the blood samples of 30 individuals, and MT-ATP8 and MT-ATP6 were amplified using PCR with specific primers. Purified PCR products were sequenced and analyzed for mutations using SnapGene and BioEdit. Bioinformatics tools, Consurf and PolyPhen-2, were used to analyze the genetic variants and their impact on protein function and stability. Results: The analysis revealed two significant mutations in MT-ATP6 gene i.e., m.8860A>G (found in all 30 out of 30 samples) which results in the variant p.(Thr112Ala) and m.8701A>G (found in 13 out of 30 samples) which results in the variant p.(Thr59Ala). PolyPhen-2 analysis reveals the benign nature of both mutations, suggesting that the sequence variants are unlikely to cause any adverse effects on protein structure and function.