Bioinformatics analysis of common mutations in the single gene-form of Parkinson's disease

چکیده مقاله

Background of the study: The inherited pattern of Parkinson's disease varies depending on the gene being altered, which is dominated by both autosomal and autosomal recessive forms. Mutations in Parkinson's disease genes cause mitochondrial dysfunction, oxidative stress, protein accumulation, and autophagic stress. In most patients, mutations in different genes, epigenetic factors, environmental factors, age, or a combination of these factors are among the main causes of the disease. Methods: For bioinformatics analysis, first, all the genes and mutations of this disease were extracted using HGMD server. Then, using POLYPHEN and SIFT site, the effect of mutations in the disease was investigated separately. Common mutations were extracted and analyzed statistically. Results: The results showed that the genes LRRK2, SNCA are inherited with the dominant autosomal inheritance pattern and PARK7, PARK2, PINK1 with the autosomal recessive pattern inherited from the patient's parent. All mutations extracted from the Polyphen and Sift 181 databases included 18 mutations in the parkin gene with 38 known mutations, but the most destructive damage was found in the LRRK2, PINK1, and then PARKIN genes. Conclusion: Over the past 10 years, the etiological conceptions of Parkinson disease have changed from an almost solely environmental mechanism to a complex disorder with major genetic contributors. Identifying responsible mutations in specific genes, particularly α-synuclein, Parkin, PINK1, DJ-1 and LRRK2, has revealed better understanding of Parkinson's disease's clinical and made pathological changes with implications for patient treatment, management and future study.