Jurnal Internasional Memahami peran variabilitas genetik di LRRK2 di populasi India – Kishore – – Gerakan Gangguan
Genetic variability in LRRK2 has really been designated as a major risk factor for family and sporadic PD forms in diverse ethnic populations. 
To complete the role of LRRK2 in the Indian population.
We conducted targeted resequencing of LRRK2 loci in 288 cases and 298 controls and completed the haplotypic LRRK2 structure in a combined cohort of 800 cases and 402 controls in the Indian population. We assessed the frequency of new missense variants in white and East Asian populations by utilizing exotic sequences and solid genotypic data, respectively. We performed computational modeling and biochemical approaches to deduce the potential role of new variants that affect the function of LRRK2 protein . Finally, we assessed the phosphorylation activities of the novel coding variants identified in the LRRK2 gene.
We identified four new missense variants with frequencies ranging from 0,0008% to 0,002% specifically for Indian residents, including the armadillo domain and protein kinase LRRK2 . The general genetic diversity in LRRK2 can contribute to increased risk, but is not significant after correcting for some tests, due to the small size of the cohort. Computational modeling shows a destabilizing effect on the LRRK2 function. Compared to wild-type, the kinase domain variant shows a 4-fold increase in kinase activity.
Our study, for the first time, identified a new missense variant for LRRK2 specifically for the Indian population, and showed that novel missense variants in the kinase domain modified kinase activity in vitro. . © 2018 International Parkinson and Society Disorder Movement