Mining the Genetic Diversity of the Pathogenic Protozoan, Neospora caninum
- Publication Type:
- Thesis
- Issue Date:
- 2020
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๐๐ฆ๐ฐ๐ด๐ฑ๐ฐ๐ณ๐ข ๐ค๐ข๐ฏ๐ช๐ฏ๐ถ๐ฎ is a cyst-forming apicomplexan parasite, responsible for economic and reproductive losses to cattle industries worldwide, and represents a serious neurological disease in canines. Although discovered over three decades ago, progress towards treatment and control strategies against neosporosis, remains stagnant. Currently, common practices to combat the disease include passivity, or expensive culling of seropositive dams. However, vaccination represents a cost-effective and efficacious option, especially using live, attenuated isolates.
Members of the Apicomplexa consist of populations that vary enormously in their disease-causing potential, where ๐ช๐ฏ ๐ท๐ช๐ท๐ฐ experiments have demonstrated pathogenic variability between ๐. ๐ค๐ข๐ฏ๐ช๐ฏ๐ถ๐ฎ isolates. The underlying question therefore, is what is the genetic basis of virulence within the species, and consequently, how can such information be exploited in vaccine development? Thus far, conventional techniques have been employed to study the intraspecies genetic diversity associated with ๐. ๐ค๐ข๐ฏ๐ช๐ฏ๐ถ๐ฎ, generally involving PCR-based approaches targeting repetitive elements. However, a direct causal relationship between such diversity and important parasite phenotypes such as virulence, is yet to be established.
Alternatively, burgeoning next generation sequencing (NGS) technologies and ๐ช๐ฏ-๐ด๐ช๐ญ๐ช๐ค๐ฐ tools have provided new opportunities to perform genome-wide scans in such organisms. Hence the objective of this body of work was to compare the genomes and transcriptomes of two distinct ๐. ๐ค๐ข๐ฏ๐ช๐ฏ๐ถ๐ฎ isolates, using NGS data and bioinformatics workflows, to identify sequence variants in coding and non-coding DNA. Annotation of variable regions would reveal potential virulence markers distinguishing isolates of this species. Challenges accompanying such research include the lack of optimisation and standardisation of NGS analysis tools for non-model organisms such as pathogenic Protozoa. This is compounded by the dubious accuracy of the ๐. ๐ค๐ข๐ฏ๐ช๐ฏ๐ถ๐ฎ reference genome, as well as the disturbingly large number of proteins described as โhypotheticalโ or โuncharacterisedโ.
This body of research represents a thesis by compilation, consisting of four publications, and one chapter under review. Each chapter represents an independent study, which collectively address the research objective and current gaps in the literature. The results present polymorphic โhotspotsโ in concentrated windows of the ๐. ๐ค๐ข๐ฏ๐ช๐ฏ๐ถ๐ฎ genome, where there is a correlation between hypervariable regions within protein-coding genes, and non-coding regions. Furthermore, an ๐ช๐ฏ-๐ด๐ช๐ญ๐ช๐ค๐ฐ pipeline is developed to annotate uncharacterised proteins, subsequently identifying a subset of proteins potentially implicated in crucial parasite mechanisms, conducive to ๐. ๐ค๐ข๐ฏ๐ช๐ฏ๐ถ๐ฎโs success. It is trusted that this thesis contributes vital knowledge pertaining to ๐. ๐ค๐ข๐ฏ๐ช๐ฏ๐ถ๐ฎ intraspecies diversity, aiding in the quest to develop a vaccine against neosporosis.
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