Title: Bioinformatics analysis of the pathogenic point mutation mt.8993T > C in the MT-ATP6 gene of mitochondrial DNA associated with Leigh syndrome
Abstract:
The mitochondrial disease often associated with various illnesses in relation to the activity of cells metabolites and the synthesis of adenosine triphosphate (ATP). Leigh syndrome part of a continuum of progressive neurodegenerative disorders caused by abnormalities of mitochondrial energy generation, including alteration in the mitochondrial DNA. The point mutation (T > C) at the same 8993 nucleotide of mitochondrial DNA (at comparable mutant load), of ATP6 gene encodes protein subunit of ATPase6, a part of ATP synthase, which is important in the electron transfer and proton translocation in intracellular respiration system result in neurological phenotypes of variable severity in humans. In silico study the sequence of MT-ATP6 gene retrieved from NCBI, it consisted from 681 bp. ATP6 protein of normal and Leigh syndrome consisted of 226 amino acids that detect by BLASTx tool (translation DAN to amino acids sequence), the amino acid sequence of ATP 6 gene in FAST format, shown the position of L (Leucine), in normal ATP 6 (adenosine triphosphate 6) protein. While the sequence of ATP 6 gene of Leigh disease consist from 681 pb, the missense mutation L173 P is the most common defect in the mt-adenosine triphosphate 6 (mt-ATP6) gene; it involves point mutation by converted the Thymine in genetic code (CTG) encode to Cytosine in genetic code (CCG), this converted the L amino acid to P amino acid. The mutations that cause Leigh syndrome impair the function or stability of the ATP synthase complex, inhibiting ATP production and impairing oxidative phosphorylation. Although the exact mechanism is unclear, researchers believe that impaired oxidative phosphorylation can lead to cell death because of decreased energy available in the cell.
Audience Take Away Notes
- The audience can use the same steps and tool to study the other SNPs of ATP6 gene and the relationship the leigh syndrome.
- This study make the audience known how the mt.8993T > C can affected on the structure of protein and how the function of protein that encod by ATP6 gene will impaired due to this SNP.
- As recored above other faculty could use to expand their research and provied a clearer vision on how the SNP can impact on the gene and protein structure and function.
