COMBINED SEQUENCE AND SEQUENCE-STRUCTURE BASED ANALYSIS OF SNPS ASSOCIATED WITH GENES INVOLVED IN PARKINSON'S DISEASE.

Abstract

Mutations in SNCA, LRRK2, PINK and DJ1 plays a very important part in pathological process of Parkinson’s disease therefore SNPs associated with these genes were picked for detailed examination of their unfavourable effects on human body. SNPs were taken from NCBI dbSNP and only missense and mutations with unknown significance were taken into consideration. To study the deleterious effect of these SNPs we followed sequence specific and sequence-structure specific methods in order to provide more accurate results. SIFT, PolyPhen2, SNP & Go and iMutant3.0 were used for detection of deleterious SNPs and MD simulations were performed using NAMD to validate the results. The study suggested that V1598E and P2119L of LRRK2 gene could indirectly or directly affect the Hydrogen bonding pattern and destabilize the amino acid interactions of gene to certain extent.