Orme, Tatiana Jasmine;
(2020)
Genetic analysis of dementia with Lewy bodies.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Dementia with Lewy bodies (DLB) is a neurodegenerative disease that shares symptoms and pathological features with both Alzheimer’s and Parkinson’s diseases. This thesis describes the genetic analysis of a large cohort of over 1,000 individuals with DLB and approximately 1,500 people without the disease. Exome sequencing was performed in this cohort in order to analyse the coding regions of the genome, in the aim to find genetic variation that may be implicated in the development of DLB. Specifically, this work used bioinformatics to process, interpret, and analyse the data generated from the sequencing. This included variant annotation, in addition to extensive quality control of the genetic data, at a cohort, and at an individual level. From here, several methods were utilized to investigate genetic variation that may be linked to DLB. This included an association analysis that focussed on rare variants within the same gene, in order to identify an enrichment of variants in either cases or controls. An additional test was conducted to analyse the burden of rare variants within specific biological pathways. Genes that are well established in the pathogenesis of DLB were also explored, along with genetic regions that have more recently been linked to disease risk. Furthermore, genes known to cause mendelian forms of related neurodegenerative diseases were examined in order to find pathogenic, disease-causing variants or novel and potentially pathogenic variants. The aim of this study was to identify genetic variants that may be causative, or impart risk to the development of DLB. A variety of methods were used to analyse variants with different allele frequencies - from novel, to more common. This is a comprehensive survey of genetic variation in a large cohort of DLB cases. By identifying genes that play a role in DLB, we can hope to learn more about the disease process.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Genetic analysis of dementia with Lewy bodies |
| Event: | UCL |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10089954 |
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