Understanding the role of genetic variability in LRRK2 in Indian population

• Verfasst von: Kishore, Asha [VerfasserIn]
• Verfasst von: Raimondi, Francesco [VerfasserIn]
• Verfasst von: Russell, Robert B. [VerfasserIn]
• Titel: Understanding the role of genetic variability in LRRK2 in Indian population
• Verf.angabe: Asha Kishore, Ashwin Ashok Kumar Sreelatha, Marc Sturm, Felix von-Zweydorf, Lasse Pihlstrøm, Francesco Raimondi, Rob Russell, Peter Lichtner, Moinak Banerjee, Syam Krishnan, Roopa Rajan, Divya Kalikavil Puthenveedu, Sun Ju Chung, International Parkinson's Disease Genomics Consortium (IPDGC), Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD), Peter Bauer, Olaf Riess, Christian Johannes Gloeckner, Rejko Kruger, Thomas Gasser, and Manu Sharma
• Jahr: 2019
• Jahr des Originals: 2018
• Umfang: 10 S.
• Fussnoten: Published online 28 November 2018 ; Gesehen am 23.10.2019
• Titel Quelle: Enthalten in: Movement disorders
• Ort Quelle: New York, NY : Wiley, 1986
• Jahr Quelle: 2019
• Band/Heft Quelle: 34(2019), 4, Seite 496-505
• ISSN Quelle: 1531-8257
• DOI: doi:10.1002/mds.27558
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: LRRK2
• Sach-SW: neurodegeneration
• Sach-SW: Parkinson's disease
• K10plus-PPN: 1679478192

Abstract

Genetic variability in LRRK2 has been unequivocally established as a major risk factor for familial and sporadic forms of PD in ethnically diverse populations. We performed targeted resequencing of the LRRK2 locus in 288 cases and 298 controls and resolved the haplotypic structure of LRRK2 in a combined cohort of 800 cases and 402 controls in the Indian population. We assessed the frequency of novel missense variants in the white and East Asian population by leveraging exome sequencing and densely genotype data, respectively. We did computational modeling and biochemical approach to infer the potential role of novel variants impacting the LRRK2 protein function. Finally, we assessed the phosphorylation activity of identified novel coding variants in the LRRK2 gene.