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Genomic surveillance of the malaria mosquito, Anopheles gambiae

Nagi, Sanjay (2023) Genomic surveillance of the malaria mosquito, Anopheles gambiae, Thesis (Doctoral), Liverpool School of Tropical Medicine.

S Nagi - PhDThesis.pdf - Accepted Version

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In this thesis, I discuss population genomics of the major malaria vector, Anopheles gambiae, with a focus on the evolution of insecticide resistance. In particular, I present a series of computational tools, applicable to both genomic and transcriptomic technologies, which I hope will enhance the research community's ability to perform effective genomic surveillance.
In the first chapter, I provide an introduction to malaria as a disease and its vector, the African malaria mosquito. I describe how we attempt to control the mosquito, the problem of insecticide resistance and how genomic surveillance may help to mitigate this problem.
In the second chapter, I present RNA-Seq-Pop, a reproducible computational snakemake pipeline applicable to Illumina RNA Sequencing data of any organism. The workflow performs typical transcriptomic analyses, but also calls SNPs and can extract population genomic signals, relating to genetic diversity, selection, ancestry and karyotypes, extending the utility of RNA-Seq and bridging the gap between transcriptomic and genomic studies.
In the third chapter, I present a python package, AgamPrimer and an accompanying Google Colaboratory notebook, which allows users to design primers and hybridisation probes for An. gambiae whilst considering genetic (SNP) variation in primer/probe binding sites.
In the fourth chapter, I describe an in-depth population genomic analysis of a locus under intense selection in An. gambiae, which displays evidence of parallel evolution in An. arabiensis, An. coluzzii, and Culex pipiens. I also present a snakemake workflow, locusPocus, which implements many of the analyses contained therein, including phylogenetic analysis, multi-allele phasing, indel calling and more.
In the fifth chapter, I describe a population genomic analysis of 485 whole-genome sequenced An. gambiae mosquitoes collected from a small region of Obuasi, Central Ghana. I identify ultra-fine-scale population structure and summarise the genomic basis of insecticide resistance in Obuasi. I present a snakemake workflow, Probe, which automates a subset of the analyses performed.
In the final chapter, I discuss the impacts of this work, and what work could be done to take this research forward. I highlight some areas in mechanisms of resistance research that may be interesting to explore in the future.
In the Appendix, I briefly describe a new software tool, AnoExpress, which summarises gene expression across published RNA-Sequencing experiments into insecticide resistance in Anopheles mosquitoes.

Item Type: Thesis (Doctoral)
Subjects: QU Biochemistry > Genetics > QU 460 Genomics. Proteomics
QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
Faculty: Department: Biological Sciences > Vector Biology Department
Depositing User: Lynn Roberts-Maloney
Date Deposited: 11 Oct 2023 10:52
Last Modified: 11 Jan 2024 04:12


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