Biology subjects

Muhanguzi, D.

Publications and source records attributed to Muhanguzi, D..

4 recordsLinked to original sources

bioRxiv2025

Assessing the population genetic structure and demographic history of Anopheles gambiae and Anopheles arabiensis at island and mainland populations in Uganda: Implications for testing novel malaria vector control approaches.

Despite substantial investments in malaria control, the disease remains a major burden in sub-Saharan Africa, particularly Uganda. Novel tools such as gene drive systems are being developed to suppress malaria vector populations, but their deployment requires detailed knowledge of mosquito population genetics. We assessed the genetic structure, diversity, and demographic history of Anopheles gambiae and Anopheles arabiensis from six sites in Uganda: three islands in Lake Victoria and three mainland sites. A total of 2918 Anopheles gambiae and 173 Anopheles arabiensis were genotyped using targeted amplicon sequencing of 62 loci across coding and non-coding regions of the genome. Population structure analyses revealed clear separation between the two species but little differentiation within each species across sites. Pairwise FST values among An. gambiae populations were low (0.00054-0.028) but often significant, with mainland populations showing higher connectivity and island populations exhibiting greater isolation. Anopheles arabiensis mainland populations showed no statistically significant differentiation, suggesting panmixia. Principal Component Analysis and Bayesian clustering similarly distinguished species-level structure but no obvious substructure within sites. Mainland An. gambiae populations displayed higher nucleotide diversity than island populations, while An. arabiensis showed the lowest diversity overall. Tajimas D values were negative across sites, consistent with recent population expansions. Effective population size estimates indicated small populations at the islands (146 to 249) compared to large mainland populations (4,054 to 8,190). These findings demonstrate strong genetic differentiation between Anopheles gambiae and Anopheles arabiensis, and subtle but meaningful structure between island and mainland Anopheles gambiae populations. The reduced diversity and small effective population sizes at island sites suggest stronger genetic drift and limited gene flow, in contrast to the highly connected mainland populations. For malaria control, this contrast has direct implications. High connectivity among mainland populations may facilitate the spread of insecticide resistance alleles, while island populations, with their relative isolation and smaller sizes, may serve as suitable sites for contained field trials of gene drive strategies. This study highlights how geographic and ecological factors shape mosquito population structure and provides critical evidence for the design and monitoring of genetic-based vector control interventions.

evolutionary biology↗

bioRxiv2023

Ticks; a reservoir for virus emergence at the human-livestock interface in Uganda

BackgroundUganda is one of the most biodiverse regions on the planet and a hotspot for virus emergence. In particular, the warm-humid lowlands favour tick population growth with the associated risk of tick-borne disease. The prevalent tick species Rhipicephalus appendiculatus, R. evertsi evertsi and Amblyomma variegatum harbour a diverse range of viruses, from harmless to highly pathogenic. Notably, the orthonairoviruses cause human outbreaks of Crimean-Congo haemorrhagic fever (CCHF) regularly within the cattle corridor of Uganda, a region spanning from the south-west to the north-east of the country. MethodsIn the ArboViral Infection (AVI) study, the first to explore the virome of ticks in Uganda using next generation sequencing (NGS), we collected ticks from three geographically diverse areas and subjected these to target-enrichment (TE) NGS. Viral genomes were detected by de novo assembly, mapping and BLASTn. ResultsWe analyzed a total of 2,754 ticks collected from 31 livestock farms in the districts of Arua, Nakaseke and Lyantonde. These were combined into 219 pools by site of collection and tick species, including R. appendiculatus, R. evertsi evertsi, A. variegatum and Hyalomma rufipes. We detected partial or near-complete viral genomes in 163 tick pools; 110 (67%) of which were from Arua, 39 (24%) from Nakaseke and 12 (7%) from Lyantonde districts. 2 pools (2%) were from Arua/Lyantonde. These included 22 species of virus, representing 15 genera and 9 families, including the Nairoviridae, Retroviridae, Orthomyxoviridae, Chuviridae, Rhabdoviridae, Phenuiviridae, Parvoviridae, Poxviridae and Flaviviridae. There were 8 viral species known to be pathogens of humans or animals and 5 highly divergent genomes detected, representing novel virus species. A high abundance of orthonairoviruses was notable, including CCHFV, Dugbe virus and a novel Orthonairovirus species that we have named Macira virus. InterpretationTicks in Uganda are an important reservoir of diverse virus species, many of which remain uncharacterised and of unknown pathogenic potential. Author SummaryTicks are parasitic arachnids that may transmit a spectrum of viral diseases to humans and animals. Uganda is a hotspot for such tick-borne diseases. In this study, we sequenced ticks collected from three geographically diverse regions of Uganda using a semi-agnostic next- generation sequencing method in order to detect viruses from all known virus families. We collected and analyzed 2,754 ticks from 31 farms across the country. Within these ticks, we detected 22 species of virus from 15 genera and 9 viral families, including 8 animal or human pathogens and 5 new novel virus species. Notably, orthonairoviruses, including the highly pathogenic Crimean-Congo haemorrhagic fever virus, were highly prevalent in the ticks. The researchers suggest that ticks in Uganda serve as an important reservoir for diverse viruses, many of which have significant pathogenic potential. This information will inform public health efforts to prevent and control tick-borne diseases in Uganda and other similar regions.

microbiology↗

bioRxiv2022

Optical mapping compendium of structural variants across global cattle breeds

Structural variants (SV) have been linked to important bovine disease phenotypes, but due to the difficulty of their accurate detection with standard sequencing approaches, their role in shaping important traits across cattle breeds is largely unexplored. Optical mapping is an alternative approach for mapping SVs that has been shown to have higher sensitivity than DNA sequencing approaches. The aim of this project was to use optical mapping to develop a high-quality database of structural variation across cattle breeds from different geographical regions, to enable further study of SVs in cattle. To do this we generated 100X Bionano optical mapping data for 18 cattle of nine different ancestries, three continents and both cattle sub-species. In total we identified 13,457 SVs, of which 1,200 putatively overlap coding regions. This resource provides a high-quality set of optical mapping-based SV calls that can be used across studies, from validating DNA sequencing-based SV calls to prioritising candidate functional variants in genetic association studies and expanding our understanding of the role of SVs in cattle evolution.

genomics↗

bioRxiv2019

In Silico Analysis of Ixodid Tick Aqauporin-1 Protein as a Candidate Anti-Tick Vaccine Antigen

Ticks are arthropod vectors of pathogens of both Veterinary and Public health importance. Ticks are largely controlled by acaricide application. However, acaricide efficacy is hampered by high cost, the need for regular application and selection of multi-acaricide resistant tick populations. In light of this, future tick control approaches are poised to rely on integration of rational acaricide application and other methods such as vaccination. To contribute to systematic research-guided efforts to produce anti-tick vaccines, we carried out an in silico tick Aquaporin-1 protein (AQP1) analysis to identify unique tick AQP1 peptide motifs that can be used in future peptide anti-tick vaccine development. We used multiple sequence alignment (MSA), motif analysis, homology modeling, and structural analysis to identify unique tick AQP1 peptide motifs. BepiPred, Chou & Fasman-Turn, Karplus & Schulz Flexibility and Parker-Hydrophilicity prediction models were used to asses these motifs abilities to induce antibody mediated immune responses. Tick AQP1 (MK334178) protein homology was largely similar to the bovine AQP1 (PDB:1J4N) (23% sequence similarity; Structural superimposition RMS=1.475). The highest similarities were observed in the transmembrane domains while differences were observed in the extra and intra cellular protein loops. Two unique tick AQP1 (MK334178) motifs, M7 (residues 106-125, p=5.4e-25) and M8 (residues 85-104, p=3.3e-24) were identified. These two motifs are located on the extra-cellular AQP1 domain and showed the highest Parker-Hydrophilicity prediction immunogenic scores of 1.153 and 2.612 respectively. The M7 and M8 motifs are a good starting point for the development of potential peptide-based anti-tick vaccine. Further analyses such as in vivo immunization assays are required to validate these findings.

bioinformatics↗