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

Background and Aim: In the last decade, six single-gene forms of Parkinson's disease have been identified. The recent research focus is to identify the function of genes and proteins involved in the genetic forms of Parkinson's disease that will help us better understand the genetic pathogenesis of the disease. This study provides a detailed analysis of mutations in the genes associated with Parkinson's disease that significantly advance our knowledge of clinical changes, brain imaging, and pathological features of the disease.Methods: Currently, reported mutations in known genes according to the Human Genome Mutations Database are available from http://www.hgmd.org. For bioinformatics analysis, all genes and mutations of this disease were first extracted using the HGMD site. Then, the effect of mutations on disease was evaluated using POLY PHEN and SIFT site separately. Common mutations were extracted and analyzed statistically.Results: According to studies on large families, genes associated with Parkinson's disease were identified as follows: SNCA, LRRK۲, DJ۱, PINK۱, PARKIN, ATP۱۳A۲, UCHL۱, HTRA۲, GIGYF۲, PLA۲G۶, FBXO۷, NR۴A۲, NCA۲, and GBA. LRRK۲, and SNCA genes with autosomal dominant inheritance pattern, and PARK۷, PARK۲, and PINK۱ genes with autosomal recessive inheritance pattern are inherited from a patient's parent. The highest known degree of mutation is in the parkin gene with ۳۸ mutations, but the most destructive damage was seen in the LRRK۲ and PINK۱ genes and then in PARKIN. The most destructive replacement is for the LRRK۲, PINK۱ genes.Conclusion: After analysis, the genes associated with Parkinson's disease were identified as follows: SNCA (a-synuclein), LRRK۲, DJ۱, PINK۱, PARKIN, and ATP۱۳A۲. Mutations in the SNCA and DJ۱ genes are rare, but mutations in PINK۱, PARKIN, and LRRK۲ are common in many patients.Identification of PINK۱, PARKIN and LRRK۲ will determine their greater role in the pathophysiology of Parkinson's disease.

Keywords:

Parkinson's disease , PARK group genes , Common mutations