Skip to main content

Analysis of Genetic Variation in Humans and Other Species

Martell, Henry (2018) Analysis of Genetic Variation in Humans and Other Species. Doctor of Philosophy (PhD) thesis, University of Kent,. (KAR id:76218)

Language: English
Download (49MB) Preview
[thumbnail of 359henry_james_martell_thesis.pdf]
This file may not be suitable for users of assistive technology.
Request an accessible format


Recent advances in sequencing technologies have led to the generation of vast amounts genetic variation data for many species, including humans, with advances in our understanding of disease now limited by the speed at which these data can be analysed. This thesis focuses on the analysis of genetic variation at multiple levels. First, in the human disease cystinuria, an inherited form of kidney stones. Genetic variants previously associated with cystinuria were characterised using a series of computational methods, identifying key functional features of these mutations. Predictions of disease severity for a cohort of 74 cystinuria patients were then made based on the genotypes of each individual. When compared to clinical outcomes, these predictions demonstrate the potential for computational methods in delivering precision medicine to cystinuria patients. Second, a genome-wide analysis of variant combinations in individual human genomes identified combinations of variants protein-wide, within close spatial proximity in the 3-dimensional structures of proteins, and in protein-protein interface sites. The vast majority of computational methods for analysing genetic variation consider only one variant at a time. This work highlights the importance of analysing the combined effects of variants, which will be a key challenge in the future of computational biology and precision medicine. Finally, two different analyses of ebolaviruses were performed. The first study focused on human pathogenicity of ebolaviruses, a critical challenge in epidemiology. This study identified a set of key variants that differentiate human pathogenic and non-pathogenic ebolaviruses. The second study focused on the evolution of the Ebola virus genome, the most common causative species of human ebolavirus outbreaks. Ebola virus genome evolution was analysed over time since its identification in 1976, and over the course of the 2013-2016 West Africa outbreak. A strong bias for transition mutations was identified, with suspected mutational pressure from host APOBEC and ADAR enzymes.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Wass, Mark
Thesis advisor: Griffin, Darren
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: Organisations -1 not found.
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 05 Sep 2019 14:30 UTC
Last Modified: 15 Dec 2022 22:10 UTC
Resource URI: (The current URI for this page, for reference purposes)
  • Depositors only (login required):


Downloads per month over past year