Thesis
Investigating Disease-causing Variants in Undiagnosed Patients
Honours, Murdoch University
2025
Abstract
The diagnostic odyssey describes the long process of reaching an accurate diagnosis for patients with rare diseases. It is estimated that 80% of rare diseases are caused by genetic variants and therefore, genetic studies are vital to the diagnostic odyssey of undiagnosed patients. Transcriptomics has improved the diagnostic success by visualising post-transcriptional changes to the genome that cannot be detected by traditional genomic sequencing. Variants of uncertain significance require functional evidence to show their effect, and this can be found in RNAsequencing (RNA-seq). This study applied RNA-seq to two undiagnosed patients to detect splicing and gene expression changes and identified two candidate genes for patient 1, ULK3 and EIF3C, and four for patient 2, RPSA, RND3, PARP2 and THOC5 with alternative splicing events. Analysis revealed evidence for the functional effects of synonymous and intronic variants on splicing in these genes, exhibiting the ability of RNA-seq in genetic pipelines. Additional genes of interest were discovered through gene expression and pathway enrichment analysis. Overall, this study demonstrates why RNA-seq, and proteomics, should be integrated into genetic studies as complementary tools to shorten the diagnostic odyssey of rare disease patients.
Details
- Title
- Investigating Disease-causing Variants in Undiagnosed Patients
- Authors/Creators
- Sophie Chapman
- Contributors
- Jessica Cale (Supervisor) - Murdoch University, Personalised Medicine CentreAnu Sooda (Supervisor) - Murdoch University, Personalised Medicine Centre
- Awarding Institution
- Murdoch University; Honours
- Identifiers
- 991005835765607891
- Murdoch Affiliation
- College of Environmental and Life Sciences
- Resource Type
- Thesis
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