Biology subjects

Mboowa, G.

Publications and source records attributed to Mboowa, G..

4 recordsLinked to original sources

bioRxiv2026

Whole-genome characterization of Plasmodium falciparum population structure and drug resistance across Uganda and neighboring countries

Uganda has one of the world's highest malaria burdens, but parasite population structure and connectivity have not been characterized nationally with whole-genome data. We analyzed 249 monoclonal Plasmodium falciparum genomes from 26 sentinel sites across Uganda in 2023 and compared them with publicly available genomes from five neighboring countries. Genetic diversity was high and differentiation low in Uganda, but identity-by-descent detected limited structure. This was most pronounced in the low-transmission southwest, where parasites shared ancestry and recent relatedness with isolates from western Tanzania. Selection scans identified signals at loci associated with resistance to artemisinins and their partner drugs, and to chloroquine and antifolates. The strongest signal was at PfPX1 where the PIN haplotype (L1222P, M1701I, D1705N) reached 70% prevalence nationwide, but selection was carried by PIN haplotypes that had additionally acquired D384A, largely confined to northern and eastern Uganda. A second substitution at the same codon, D384Y, formed a haplotype shared across the Tanzanian border. PfKelch13 variants were partitioned across multiple backgrounds, consistent with repeated independent emergence, and C469Y was enriched on the PfPX1 D384A-PIN background. These genomes provide a 2023 baseline for tracking potential mediators of drug resistance and support coordinated genomic surveillance across Uganda and its neighbors.

genomics↗

bioRxiv2024

High KIR diversity in Uganda and Botswana children living with HIV

Killer-cell immunoglobulin-like receptors (KIRs) are essential components of the innate immune system found on the surfaces of natural killer (NK) cells. The KIRs encoding genes are located on chromosome 19q13.4 and are genetically diverse across populations. KIRs are associated with various disease states including HIV progression, and are linked to transplantation rejection and reproductive success. However, there is limited knowledge on the diversity of KIRs from Uganda and Botswana HIV-infected paediatric cohorts, with high endemic HIV rates. We used next-generation sequencing technologies on 312 (246 Uganda, 66 Botswana) samples to generate KIR allele data and employed customised bioinformatics techniques for allelic, allotype and disease association analysis. We show that these sample sets from Botswana and Uganda have different KIRs of different diversities. In Uganda, we observed 147 vs 111 alleles in the Botswana cohort, which had a more than 1 % frequency. We also found significant deviation towards homozygosity for the KIR3DL2 gene for both rapid (RPs) and long-term non-progressors (LTNPs)in the Ugandan cohort. The frequency of the bw4-80I ligand was also significantly higher among the LTNPs than RPs (8.9 % Vs 2.0%, P-value: 0.032). In the Ugandan cohort, KIR2DS4*001 (OR: 0.671, 95 % CI: 0.481-0.937, FDR adjusted Pc=0.142) and KIR2DS4*006 (OR: 2.519, 95 % CI: 1.085-5.851, FDR adjusted Pc=0.142) were not associated with HIV disease progression after adjustment for multiple testing. Our study results provide additional knowledge of the genetic diversity of KIRs in African populations and provide evidence that will inform future immunogenetics studies concerning human disease susceptibility, evolution and host immune responses.

genomics↗

bioRxiv2021

Genetic Diversity of Bundibugyo Ebolavirus from Uganda and the Democratic Republic of Congo

BackgroundThe Ebolavirus is one of the deadliest viral pathogens which was first discovered in the year 1976 during two consecutive outbreaks in the Democratic Republic of Congo and Sudan. Six known strains have been documented. The Bundibugyo Ebolavirus in particular first emerged in the year 2007 in Uganda. This outbreak was constituted with 116 human cases and 39 laboratory confirmed deaths. After 5 years, it re-emerged and caused an epidemic for the first time in the Democratic Republic of Congo in the year 2012 as reported by the WHO. Here, 36 human cases with 13 laboratory confirmed deaths were registered. Despite several research studies conducted in the past, there is still scarcity of knowledge available on the genetic diversity of Bundibugyo Ebolavirus. We undertook a research project to provide insights into the unique variants of Bundibugyo Ebolavirus that circulated in the two epidemics that occurred in Uganda and the Democratic Republic of Congo Materials and MethodsThe Bioinformatics approaches used were; Quality Control, Reference Mapping, Variant Calling, Annotation, Multiple Sequence Alignment and Phylogenetic analysis to identify genomic variants as well determine the genetic relatedness between the two epidemics. Overall, we used 41 viral sequences that were retrieved from the publicly available sequence database, which is the National Center for Biotechnology and Information Gen-bank database. ResultsOur analysis identified 14,362 unique genomic variants from the two epidemics. The Uganda isolates had 5,740 unique variants, 75 of which had high impacts on the genomes. These were 51 frameshift, 15 stop gained, 5 stop lost, 2 missense, 1 synonymous and 1 stop lost and splice region. Their effects mainly occurred within the L-gene region at reference positions 17705, 11952, 11930 and 11027. For the DRC genomes, 8,622 variant sites were identified. The variants had a modifier effect on the genome occurring at reference positions, 213, 266 and 439. Examples are C213T, A266G and C439T. Phylogenetic reconstruction identified two separate and unique clusters from the two epidemics. ConclusionOur analysis provided further insights into the genetic diversity of Bundibugyo Ebolavirus from the two epidemics. The Bundibugyo Ebolavirus strain was genetically diverse with multiple variants. Phylogenetic reconstruction identified two unique variants. This signified an independent spillover event from a natural reservoir, rather a continuation from the ancestral outbreak that initiated the resurgence in DRC in the year 2012. Therefore, the two epidemics were not genetically related.

genomics↗

bioRxiv2020

Whole-genome sequence analysis reveals evolution of antimicrobial resistance in a Ugandan colistin resistant Acinetobacter baumannii

In recent times, pan-drug resistant Acinetobacter baumannii have emerged and continue to spread among critically ill patients, this poses an urgent risk to global and local human health. This study sought to provide the first genomic analysis of a pan-drug resistant Acinetobacter baumannii from Uganda and Africa, and to tell a story of mobile genetic element-mediated antibiotic resistance evolution in the isolate. It was an in-silico study in which intrinsic and acquired antibiotic resistance genes, and/or chromosomal resistance mutations were identified using PATRIC, CARD, NDARO and ResFinder. Screening for insertion sequences was done using ISfinder. Also, plasmid screening, phylogenetic analysis and sequence typing were performed using PlasmidFinder, PATRIC and Gubbin, and MLST respectively. The isolate belonged to the Sequence type 136, belonging to Clonal complex 208 and Global complex 2. This isolate shared close homology with strains from Tanzania. Resistance in the isolate was chromosomally and mobile genetic element-mediated by Acinetobacter-derived cephalosporinases and carbapenem hydrolyzing class D {beta}-lactamses, blaOXA-2, 51, 5 88, 317, blaADC-2, 25. Colistin resistance was associated with previously documented mutants, lpxA and lpxC. Other key resistance genes identified were: aph(3")-lb, aph(6)-ld, aph(3)-la, aac(3)-lld, aac(3)-lla, aph(3)-l, aph(3")-l, aph(6)-lc, aph(6)-ld, aac(3)-II, III, IV, VI, VIII, IX, X, macA, macB, tetA, tetB, tetR, dfrA, and those of the floR family. RSF1010 like IncQ broad-host-range plasmids and features of pACICU1, pACICU2, and p3ABAYE Acinetobacter baumannii plasmids namely partitioning proteins ParA and B were present. Insertion sequences present included IS3, IS5, IS66 and those of the ISLre2 families. The study described for the first time a pan-drug resistant Acinetobacter baumannii from Uganda, and told a story of mobile genetic element-mediated antibiotic resistance evolution in the isolate despite being limited by pan-drug resistance phenotypic data. It provides a basis to track trends in antibiotic resistance and identification of emerging resistance patterns in Acinetobacter baumannii in Uganda.

genomics↗