Detecting somatic mutations in UK Parkinson's disease patient brain samples using whole exome sequencing (WES)

• Main Author: Mok, Chin Yi
• Other Authors: Foo Jia Nee
• Format: Final Year Project
• Language: English
• Published: 2019
• Subjects: Science::Biological sciences::Genetics
• Online Access: http://hdl.handle.net/10356/78856
• Institution: Nanyang Technological University

Parkinson’s disease is a neurological disorder mainly caused by the depletion of dopaminergic neuronal cells in the substantia nigra, which is often the main site of pathogenesis. Although it has affected many patients worldwide over the years, mechanisms underlying neuronal loss remained largely unknown. We aimed to identify somatic or germline variants that may underlie the disease and are found either in PARK genes, or in genes related to neurological and lysosomal disorders in brains of Parkinson’s disease patients. Postmortem brain tissue samples from the substantia nigra were obtained from the Parkinson’s UK Brain Bank, and were subjected to high coverage whole exome sequencing. We identified a G2019S variant within the LRRK2 gene in a patient control who did not exhibit PD neuropathology. A stop-gain R772* mutation in LRRK2, as well as missense F52S variant in DCTN1, R5H and A3T variants in SPC24 were found in DNA isolated from the brain samples. Besides the G2019S variant, others were possible loss-of-function mutations which could have caused the encoded proteins to lose their normal function. Further work is necessary to determine whether these mutations can explain clinical symptoms related to the disease, or explain neuropathology observed in the brains of patient donors.