Detecting somatic mutations in UK Parkinson's disease patient brain samples using whole exome sequencing (WES)
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 un...
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| Format: | Final Year Project (FYP) |
| Language: | English |
| Published: |
2019
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| Online Access: | http://hdl.handle.net/10356/78856 |
| _version_ | 1811677354198564864 |
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| author | Mok, Chin Yi |
| author2 | Foo Jia Nee |
| author_facet | Foo Jia Nee Mok, Chin Yi |
| author_sort | Mok, Chin Yi |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T02:36:02Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/78856 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:36:02Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/788562023-02-28T18:01:57Z Detecting somatic mutations in UK Parkinson's disease patient brain samples using whole exome sequencing (WES) Mok, Chin Yi Foo Jia Nee School of Biological Sciences Science::Biological sciences::Genetics 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. Bachelor of Science in Biological Sciences 2019-08-14T00:49:05Z 2019-08-14T00:49:05Z 2019 Final Year Project (FYP) http://hdl.handle.net/10356/78856 en Nanyang Technological University 45 p. application/pdf |
| spellingShingle | Science::Biological sciences::Genetics Mok, Chin Yi Detecting somatic mutations in UK Parkinson's disease patient brain samples using whole exome sequencing (WES) |
| title | Detecting somatic mutations in UK Parkinson's disease patient brain samples using whole exome sequencing (WES) |
| title_full | Detecting somatic mutations in UK Parkinson's disease patient brain samples using whole exome sequencing (WES) |
| title_fullStr | Detecting somatic mutations in UK Parkinson's disease patient brain samples using whole exome sequencing (WES) |
| title_full_unstemmed | Detecting somatic mutations in UK Parkinson's disease patient brain samples using whole exome sequencing (WES) |
| title_short | Detecting somatic mutations in UK Parkinson's disease patient brain samples using whole exome sequencing (WES) |
| title_sort | detecting somatic mutations in uk parkinson s disease patient brain samples using whole exome sequencing wes |
| topic | Science::Biological sciences::Genetics |
| url | http://hdl.handle.net/10356/78856 |
| work_keys_str_mv | AT mokchinyi detectingsomaticmutationsinukparkinsonsdiseasepatientbrainsamplesusingwholeexomesequencingwes |