Bio

Bio

Mobegi is a Senior Lecturer at the department of Biochemistry, University of Nairobi. He graduated in 2014 with a PhD from University of London, London School of Hygiene and Tropical Medicine. His PhD training was supported by Medical Research Council (UK). His PhD research focused on genome-wide analysis of Plasmodium falciparum to identify signatures of natural selection.

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Publications


2022

Wangui, J, Nokes JD, Mobegi VA, Otieno JR, Agoti CN, Ngeranwa JJN, Bulimo WD.  2022.  Spatial-temporal distribution and sequence diversity of group a human respiratory syncytial viruses in Kenya preceding the emergence of {ON1} genotype, may. Influenza Other Respi. Viruses. 16:501–510., Number 3: Wiley Abstract

BACKGROUND: Human respiratory syncytial virus (HRSV) is a major cause of severe viral acute respiratory illness and contributes significantly to severe pneumonia cases in Africa. Little is known about its spatial-temporal distribution as defined by its genetic diversity. METHODS: A retrospective study conducted utilizing archived nasopharyngeal specimens from patients attending outpatient clinics in hospitals located in five demographically and climatically distinct regions of Kenya; Coast, Western, Highlands, Eastern and Nairobi. The viral total RNA was extracted and tested using multiplex real time RT-PCR (reverse transcriptase polymerase chain reaction). A segment of the G-gene was amplified using one-step RT-PCR and sequenced by Sanger di-deoxy method. Bayesian analysis of phylogeny was utilized and subsequently median joining methods for haplotype network reconstruction. RESULTS: Three genotypes of HRSVA were detected; GA5 (14.0%), GA2 (33.1%), and NA1 (52.9%). HRSVA prevalence varied by location from 33% to 13.2% in the Highlands and the Eastern regions respectively. The mean nucleotide diversity (Pi[$π$]) varied by genotype: highest of 0.018 for GA5 and lowest of 0.005 for NA1. A total of 58 haplotypes were identified (GA5 10; GA2 20; NA1 28). These haplotypes were introduced into the population locally by single haplotypes and additional subsidiary seeds amongst the GA2 and the NA1 haplotypes. CONCLUSIONS: HRSVA was found across all the regions throughout the study period and comprised three genotypes; GA5, GA2, and NA1 genotypes. The genotypes were disproportionately distributed across the regions with GA5 gradually increasing toward the Western zones and decreasing toward the Eastern zones of the country.

2021

Diarra, H, Makhulu EE, Odhiambo PO, Irekwa RM, Kinyua J, Herren JK, Mobegi VA.  2021.  Molecular Investigation of Genetic Signatures of Selection in Plasmodium falciparum Actin-Binding Protein Coronin, Cysteine Desulfurase, and Plasmepsin 2 Gene in Mbita Field Isolates, Western Kenya. Open Journal of Genetics. 11(4):120-144.
MalariaGEN, Ahouidi A, Ali M, Almagro-Garcia J, Amambua-Ngwa A, Amaratunga C, Amato R, Amenga-Etego L, Andagalu B, Anderson TJC et al..  2021.  An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples. Wellcome Open Res.. 6:42.: F1000 Research Ltd Abstract

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

2020

Nyang'au, EM, Bulimo WD, Mobegi V, Opanda S, Magiri E.  2020.  Genetic analysis of {HA1} domain of influenza {A/H3N2} viruses isolated in Kenya during the 2007-2013 seasons reveal significant divergence from {WHO-recommended} vaccine strains. Int. J. Infect. Dis.. 95:413–420.: Elsevier BV Abstract

BACKGROUND: Influenza viruses evolve rapidly and cause regular seasonal epidemics in humans challenging effective vaccination. The virus surface HA glycoprotein is the primary target for the host immune response. Here, we investigated the vaccine efficacy and evolution patterns of human influenza A/H3N2 viruses that circulated in Kenyan in the period before and after the 2009 A/H1N1 pandemic, targeting the HA1 domain. MATERIALS AND METHODS: A hundred and fifteen HA sequences of Kenyan virus viruses were analyzed relative to the corresponding WHO vaccine reference strains using bioinformatics approaches. RESULTS: Our analyses revealed varied amino acid substitutions at all the five antigenic sites (A-E) of the HA1 domain, with a majority the changes occurring at sites A and B. The Kenyan A/H3N2 viruses isolated during 2007/2008 seasons belonged to A/Brisbane/10/2007-like viruses lineage, while those circulating in 2009-2012 belonged to the lineage of A/Victoria/361/2011-like viruses. The 2013 viruses clustered in clade 3C.3 of the A/Samara/73/2013-like viruses. The mean evolutionary rate of the A/H3N2 viruses analyzed in the study was at 4.17$\times$10-3 (95% HPD=3.09$\times$10-3-5.31$\times$10-3) nucleotide substitutions per site per year, whereas the TMRCA was estimated at 11.18 (95% HPD=9.00-14.12) years ago from 2013. The prediction of vaccine efficacy revealed modest vaccine efficaciousness during 2008, and 2010 influenza seasons, whilst sub-optimal effectiveness was registered in 2007, 2009, 2012 and 2013. Further, the overall selective pressure acting on the HA1 domain was estimated at 0.56 ($ømega$<1), suggesting that a majority of codon sites in the HA1 epitopes were evolving under purifying selection. CONCLUSIONS: Generally, our results highlight the genetic plasticity of A/H3N2 viruses and reveal considerable disparity in vaccine efficaciousness against the A/H3N2 viruses that circulated in Kenya, specifically during 2007, 2009, 2012, and 2013 influenza seasons. Our findings underscore the importance and need for consistent surveillance and molecular characterization of influenza viruses, to inform decision making and enhance early of detection of strains with epidemic/pandemic potential as well as benefit in guiding decisions regarding the appropriate annual influenza vaccine formulations.

Bungei, JK, Mobegi VA, Nyanjom SG.  2020.  Single-nucleotide polymorphism characterization of gametocyte development 1 gene in Plasmodium falciparum isolates from Baringo, Uasin Gishu, and Nandi Counties, Kenya, mar. Heliyon. 6:e03453., Number 3: Elsevier BV Abstract

INTRODUCTION: Plasmodium falciparum relies on gametocytogenesis to transmit from humans to mosquitoes. Gametocyte development 1 (Pfgdv1) is an upstream activator and epigenetic controller of gametocytogenesis. The emergence of drug resistance is a major public health concern and this requires the development of new strategies that target the transmission of malaria. As a putative drug target, Pfgdv1 has not been characterized to identify its polymorphisms and alleles under selection and how such polymorphisms influence protein structure. METHODS: This study characterized single-nucleotide polymorphisms (SNPs) in primary sequences (n = 30) of Pfgdv1 gene generated from thirty blood samples collected from patients infected with P. falciparum and secondary sequences (n = 216) retrieved from PlasmoDB. ChromasPro, MUSCLE, Tajima's D statistic, SLAC, and STRUM were used in editing raw sequences, performing multiple sequence alignment (MSA), identifying signatures of selection, detecting codon sites under selection pressure, and determining the effect of SNPs, respectively. RESULTS: MSA of primary and secondary sequences established the existence of five SNPs, consisting of four non-synonymous substitutions (nsSNPs) (p.P217H, p.R398Q, p.H417N, and p.D497E), and a synonymous substitution (p.S514S). The analysis of amino acid changes reveals that p.P217H, p.R398Q, and p.H417N comprise non-conservative changes. Tajima's D statistic showed that these SNPs were under balancing selection, while SLAC analysis identified p.P217H to be under the strongest positive selection. . Further analysis based on thermodynamics indicated that p.P217H has a destabilizing effect, while p.R398Q and p.D497E have stabilizing effects on the protein structure. CONCLUSIONS: The existence of four nsSNPs implies that Pfgdv1 has a minimal diversity in the encoded protein. Selection analysis demonstrates that these nsSNPs are under balancing selection in both local and global populations. However, p.P217H exhibits positive directional selection consistent with previous reports where it showed differentiatial selection of P. falciparum in low and high transmission regions. Therefore, in-silico prediction and experimental determination of protein structure are necessary to evaluate Pfgdv1 as a target candidate for drug design and development.

Touray, AO, Mobegi VA, Wamunyokoli F, Herren JK.  2020.  Diversity and Multiplicity of P. falciparum infections among asymptomatic school children in Mbita, Western Kenya. Sci. Rep.. 10:5924., Number 1: Springer Science and Business Media LLC Abstract

Multiplicity of infection (MOI) and genetic diversity of P. falciparum infections are important surrogate indicators for assessing malaria transmission intensity in different regions of endemicity. Determination of MOI and diversity of P. falciparum among asymptomatic carriers will enhance our understanding of parasite biology and transmission to mosquito vectors. This study examined the MOI and genetic diversity of P. falciparum parasite populations circulating in Mbita, a region characterized as one of the malaria hotspots in Kenya. The genetic diversity and multiplicity of P. falciparum infections in 95 asymptomatic school children (age 5-15 yrs.) residing in Mbita, western Kenya were assessed using 10 polymorphic microsatellite markers. An average of 79.69% (Range: 54.84-95.74%) of the isolates analysed in this study were polyclonal infections as detected in at least one locus. A high mean MOI of 3.39 (Range: 2.24-4.72) and expected heterozygosity (He) of 0.81 (Range: 0.57-0.95) was reported in the study population. The analysed samples were extensively polyclonal infections leading to circulation of highly genetically diverse parasite populations in the study area. These findings correlated with the expectations of high malaria transmission intensity despite scaling up malaria interventions in the area thereby indicating the need for a robust malaria interventions particularly against asymptomatic carriers in order to attain elimination in the region.

Touray, AO, Mobegi VA, Wamunyokoli F, Butungi H, Herren JK.  2020.  Prevalence of asymptomatic P. falciparum gametocyte carriage among school children in Mbita, Western Kenya and assessment of the association between gametocyte density, multiplicity of infection and mosquito infection prevalence. Wellcome Open Res.. 5:259.: F1000 Research Ltd Abstract

Background: Asymptomatic Plasmodium falciparum gametocyte carriers are reservoirs for sustaining transmission in malaria endemic regions. Gametocyte presence in the host peripheral blood is a predictor of capacity to transmit malaria. However, it does not always directly translate to mosquito infectivity. Factors that affect mosquito infectivity include, gametocyte sex-ratio and density, multiplicity of infection (MOI), and host and vector anti-parasite immunity. We assess the prevalence of gametocyte carriage and some of its associated risk factors among asymptomatic schoolchildren in Western Kenya and to further analyse the association between gametocyte density, multiplicity of infection (MOI) and mosquito infection prevalence. Methods: P. falciparum parasite infections were detected by RDT (Rapid Diagnostic Test) and microscopy among schoolchildren (5-15 years old). Blood from 37 microscopy positive gametocyte carriers offered to laboratory reared An. gambiae s.l. mosquitoes. A total of 3395 fully fed mosquitoes were screened for Plasmodium sporozoites by ELISA. P. falciparum was genotyped using 10 polymorphic microsatellite markers. The association between MOI and gametocyte density and mosquito infection prevalence was investigated. Results: A significantly higher prevalence of P. falciparum infection was found in males 31.54% (764/2422) ( p-value < 0.001) compared to females 26.72% (657/2459). The microscopic gametocyte prevalence among the study population was 2% (84/4881). Children aged 5-9 years have a higher prevalence of gametocyte carriage (odds ratios = 2.1 [95% CI = 1.3-3.4

Mutisya, JM, Mobegi VA, Kinyua JK, Kivecu MN, Okoth RO, Chemwor GC, Mwakio EW, Cheruiyot AC, Yeda RA, Okello CO, Juma JA, Opot BH, Juma DW, Roth AL, Akala HM, Andagalu BM.  2020.  Characterization of sulfated polysaccharide activity against virulent Plasmodium falciparum {PHISTb/RLP1} protein. F1000Res.. 9:1268.: F1000 Research Ltd Abstract

Background: The emergence of artemisinin resistance in South East Asia calls for urgent discovery of new drug compounds that have antiplasmodial activity. Unlike the classical compound screening drug discovery methods, the rational approach involving targeted drug discovery is less cumbersome and therefore key for innovation of new antiplasmodial compounds. Plasmodium falciparum (Pf) utilizes the process of host erythrocyte remodeling using Plasmodium-helical interspersed sub-telomeric domain (PHIST) containing proteins, which are amenable drug targets. The aim of this study is to identify inhibitors of PHIST from sulfated polysaccharides as new antimalarials. Methods: 251 samples from an ongoing study of epidemiology of malaria and drug resistance sensitivity patterns in Kenya were sequenced for PHISTb/RLP1 gene using Sanger sequencing. The sequenced reads were mapped to the reference Pf3D7 protein sequence of PHISTb/RLP1 using CLC Main Workbench. Homology modeling of both reference and mutant protein structures was achieved using the LOMETs tool. The models were refined using ModRefiner for energy minimization. Ramachandran plot was generated by ProCheck to assess the conformation of amino acids in the protein model. Protein binding sites predictions were assessed using FT SITE software. We searched for prospective antimalarials from PubChem. Docking experiments were achieved using AutoDock Vina and analysis results visualized in PyMOL. Results: Sanger sequencing generated 86 complete sequences. Upon mapping of the sequences to the reference, 12 non-synonymous single nucleotide polymorphisms were considered for mutant protein structure analysis. Eleven drug compounds with antiplasmodial activity were identified. Both modeled PHISTb/RLP1 reference and mutant structures had a Ramachandran score of >90% of the amino acids in the favored region. Ten of the drug compounds interacted with amino acid residues in PHISTb and RESA domains, showing potential activity against these proteins. Conclusion: This research identifies inhibitors of exported proteins that can be used in in vitro tests against the Plasmodium parasite.

Nyataya, J, Waitumbi J, Mobegi VA, Noreddin A, El Zowalaty ME.  2020.  Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions and their implications in malaria control, may. Diseases. 8:15., Number 2: MDPI AG Abstract

Malaria remains the biggest threat to public health, especially among pregnant women and young children in sub-Saharan Africa. Prompt and accurate diagnosis is critical for effective case management and detection of drug resistance. Conventionally, microscopy and rapid diagnostic tests (RDTs) are the tools of choice for malaria diagnosis. RDTs are simple to use and have been extensively used in the diagnosis of malaria among travelers to malaria-endemic regions, routine case management, and surveillance studies. Most RDTs target the histidine-rich protein (PfHRP) which is exclusively found in Plasmodium falciparum and a metabolic enzyme Plasmodium lactate dehydrogenase (pLDH) which is common among all Plasmodium species. Other RDTs incorporate the enzyme aldolase that is produced by all Plasmodium species. Recently, studies have reported false-negative RDTs primarily due to the deletion of the histidine-rich protein (pfhrp2 and pfhrp3) genes in field isolates of P. falciparum. Herein, we review published literature to establish pfhrp2/pfhrp3 deletions, the extent of these deletions in different geographical regions, and the implication in malaria control. We searched for publications on pfhrp2/pfhrp3 deletions and retrieved all publications that reported on this subject. Overall, 20 publications reported on pfhrp2/pfhrp3 deletions, and most of these studies were done in Central and South America, with very few in Asia and Africa. The few studies in Africa that reported on the occurrence of pfhrp2/pfhrp3 deletions rarely evaluated deletions on the flanking genes. More studies are required to evaluate the existence and extent of these gene deletions, whose presence may lead to delayed or missed treatment. This information will guide appropriate diagnostic approaches in the respective areas.

Herren, JK, Mbaisi L, Mararo E, Makhulu EE, Mobegi VA, Butungi H, Mancini MV, Oundo JW, Teal ET, Pinaud S, Lawniczak MKN, Jabara J, Nattoh G, Sinkins SP.  2020.  A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes. Nat. Commun.. 11:2187., Number 1: Springer Science and Business Media LLC Abstract

A possible malaria control approach involves the dissemination in mosquitoes of inherited symbiotic microbes to block Plasmodium transmission. However, in the Anopheles gambiae complex, the primary African vectors of malaria, there are limited reports of inherited symbionts that impair transmission. We show that a vertically transmitted microsporidian symbiont (Microsporidia MB) in the An. gambiae complex can impair Plasmodium transmission. Microsporidia MB is present at moderate prevalence in geographically dispersed populations of An. arabiensis in Kenya, localized to the mosquito midgut and ovaries, and is not associated with significant reductions in adult host fecundity or survival. Field-collected Microsporidia MB infected An. arabiensis tested negative for P. falciparum gametocytes and, on experimental infection with P. falciparum, sporozoites aren't detected in Microsporidia MB infected mosquitoes. As a microbe that impairs Plasmodium transmission that is non-virulent and vertically transmitted, Microsporidia MB could be investigated as a strategy to limit malaria transmission.

2019

Mpatswenumugabo, JPM, Bebora LC, Gitao GC, Mobegi VA, Iraguha B, Shumbusho B.  2019.  Assessment of bacterial contamination and milk handling practices along the raw milk market chain in the north-western region of Rwanda. African Journal of Microbiology Research. 13(29):640-648.

2017

Mpatswenumugabo, JP, Bebora LC, Gitao GC, Mobegi VA, Iraguha B, Kamana O, Shumbusho B.  2017.  Prevalence of subclinical mastitis and distribution of pathogens in dairy farms of Rubavu and Nyabihu districts, Rwanda, jul. J. Vet. Med.. 2017:8456713.: Hindawi Limited Abstract

A cross-sectional study was conducted from May 2016 to January 2017 in Rubavu and Nyabihu districts, Western Rwanda, aiming at estimating the prevalence of subclinical mastitis (SCM) and identifying its causative bacteria. Management practices and milking procedures were recorded through a questionnaire. 123 crossbreed milking cows from 13 dairy farms were randomly selected and screened for SCM using California Mastitis Test (CMT). Composite CMT positive milk samples were processed for bacterial isolation and identification. The overall SCM prevalence at cow level was 50.4%. 68 bacterial isolates were identified by morphological and biochemical characteristics. They included, Coagulase Negative Staphylococci (51.5%), Staphylococcus aureus (20.6%), Streptococcus species (10.3%), Bacillus species (10.3%), Streptococcus agalactiae (5.8%), and Escherichia coli (1.5%). About 67.1% of the farmers checked for mastitis; of these, 58.9% relied on clinical signs and only 6.8% screened with CMT. Only 5.5% and 2.7% of the farmers tried to control mastitis using dry cow therapy and teat dips, respectively. Thus, to reduce the prevalence of SCM, farmers in the study area need to be trained on good milking practices, including regular use of teat dips, application of dry cow therapy, and SCM screening. This will improve their sales and their financial status.

2016

Murray, L, Mobegi VA, Duffy CW, Assefa SA, Kwiatkowski DP, Laman E, Loua KM, Conway DJ.  2016.  Microsatellite genotyping and genome-wide single nucleotide polymorphism-based indices of Plasmodium falciparum diversity within clinical infections, may. Malar. J.. 15:275., Number 1: Springer Nature Abstract

BACKGROUND: In regions where malaria is endemic, individuals are often infected with multiple distinct parasite genotypes, a situation that may impact on evolution of parasite virulence and drug resistance. Most approaches to studying genotypic diversity have involved analysis of a modest number of polymorphic loci, although whole genome sequencing enables a broader characterisation of samples. METHODS: PCR-based microsatellite typing of a panel of ten loci was performed on Plasmodium falciparum in 95 clinical isolates from a highly endemic area in the Republic of Guinea, to characterize within-isolate genetic diversity. Separately, single nucleotide polymorphism (SNP) data from genome-wide short-read sequences of the same samples were used to derive within-isolate fixation indices (F ws), an inverse measure of diversity within each isolate compared to overall local genetic diversity. The latter indices were compared with the microsatellite results, and also with indices derived by randomly sampling modest numbers of SNPs. RESULTS: As expected, the number of microsatellite loci with more than one allele in each isolate was highly significantly inversely correlated with the genome-wide F ws fixation index (r = -0.88, P 10 % had high correlation (r > 0.90) with the index derived using all SNPs. CONCLUSIONS: Different types of data give highly correlated indices of within-infection diversity, although PCR-based analysis detects low-level minority genotypes not apparent in bulk sequence analysis. When whole-genome data are not obtainable, quantitative assay of ten or more SNPs can yield a reasonably accurate estimate of the within-infection fixation index (F ws).

MalariaGEN Plasmodium falciparum Community Project.  2016.  Genomic epidemiology of artemisinin resistant malaria. Elife. 5 Abstract

The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of variations that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelch13 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.

2015

Amato, R, Miotto O, Woodrow C, Almagro-Garcia J, Sinha I, Campino S, Mead D, Drury E, Kekre M, Sanders M, Amambua-Ngwa A, Amaratunga C, Amenga-Etego L, Anderson TJC, Andrianaranjaka V, Apinjoh T, Ashley E, Auburn S, Awandare GA, Baraka V, Barry A, Boni MF, Borrmann S, Teun Bousema, Branch O, Bull PC, Chotivanich K, Conway DJ, Craig A, Day NP, Djimdé A, Dolecek C, Dondorp AM, Drakeley C, Duffy P, Echeverri-Garcia DF, Egwang TG, Fairhurst RM, Faiz MA, Fanello CI, Hien TT, Hodgson A, Imwong M, Ishengoma D, Lim P, Lon C, Marfurt J, Marsh K, Mayxay M, Mobegi V, Mokuolu O, Montgomery J, Mueller I, Kyaw MP, Newton PN, Nosten F, Noviyanti R, Nzila A, Ocholla H, Oduro A, Onyamboko M, Ouedraogo J-B, Phyo AP, Plowe CV, Price RN, Pukrittayakamee S, Randrianarivelojosia M, Ringwald P, Ruiz L, Saunders D, Shayo A, Siba P, Takala-Harrison S, Thanh T-NN, Thathy V, Verra F, White NJ, Htut Y, Cornelius VJ, Giacomantonio R, Muddyman D, Henrichs C, Malangone C, Jyothi D, Pearson RD, Rayner JC, McVean G, Rockett K, Miles A, Vauterin P, Jeffery B, Manske M, Stalker J, MacInnis B, Kwiatkowski DP,, J.N Kiiru.  2015.  Genomic epidemiology of the current wave of artemisinin resistant malaria, 2015/05/24. bioRxiv. AbstractWebsite

Artemisinin resistant Plasmodium falciparum is advancing across Southeast Asia in a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non‐synonymous mutations, many of which cause radical amino‐acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of standing variation that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelch13 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.

2014

Mobegi, VA, Duffy CW, Amambua-Ngwa A, Loua KM, Laman E, Nwakanma DC, MacInnis B, Aspeling-Jones H, Murray L, Clark TG, Kwiatkowski DP, Conway DJ.  2014.  Genome-wide analysis of selection on the malaria parasite Plasmodium falciparum in West African populations of differing infection endemicity, jun. Mol. Biol. Evol.. 31:1490–1499., Number 6 Abstract

Locally varying selection on pathogens may be due to differences in drug pressure, host immunity, transmission opportunities between hosts, or the intensity of between-genotype competition within hosts. Highly recombining populations of the human malaria parasite Plasmodium falciparum throughout West Africa are closely related, as gene flow is relatively unrestricted in this endemic region, but markedly varying ecology and transmission intensity should cause distinct local selective pressures. Genome-wide analysis of sequence variation was undertaken on a sample of 100 P. falciparum clinical isolates from a highly endemic region of the Republic of Guinea where transmission occurs for most of each year and compared with data from 52 clinical isolates from a previously sampled population from The Gambia, where there is relatively limited seasonal malaria transmission. Paired-end short-read sequences were mapped against the 3D7 P. falciparum reference genome sequence, and data on 136,144 single nucleotide polymorphisms (SNPs) were obtained. Within-population analyses identifying loci showing evidence of recent positive directional selection and balancing selection confirm that antimalarial drugs and host immunity have been major selective agents. Many of the signatures of recent directional selection reflected by standardized integrated haplotype scores were population specific, including differences at drug resistance loci due to historically different antimalarial use between the countries. In contrast, both populations showed a similar set of loci likely to be under balancing selection as indicated by very high Tajima's D values, including a significant overrepresentation of genes expressed at the merozoite stage that invades erythrocytes and several previously validated targets of acquired immunity. Between-population FST analysis identified exceptional differentiation of allele frequencies at a small number of loci, most markedly for five SNPs covering a 15-kb region within and flanking the gdv1 gene that regulates the early stages of gametocyte development, which is likely related to the extreme differences in mosquito vector abundance and seasonality that determine the transmission opportunities for the sexual stage of the parasite.

2012

Mobegi, VA, Loua KM, Ahouidi AD, Satoguina J, Nwakanma DC, Amambua-Ngwa A, Conway DJ.  2012.  Population genetic structure of Plasmodium falciparum across a region of diverse endemicity in West Africa, jul. Malar. J.. 11:223., Number 1: Springer Science and Business Media LLC Abstract

BACKGROUND: Malaria parasite population genetic structure varies among areas of differing endemicity, but this has not been systematically studied across Plasmodium falciparum populations in Africa where most infections occur. METHODS: Ten polymorphic P. falciparum microsatellite loci were genotyped in 268 infections from eight locations in four West African countries (Republic of Guinea, Guinea Bissau, The Gambia and Senegal), spanning a highly endemic forested region in the south to a low endemic Sahelian region in the north. Analysis was performed on proportions of mixed genotype infections, genotypic diversity among isolates, multilocus standardized index of association, and inter-population differentiation. RESULTS: Each location had similar levels of pairwise genotypic diversity among isolates, although there were many more mixed parasite genotype infections in the south. Apart from a few isolates that were virtually identical, the multilocus index of association was not significant in any population. Genetic differentiation between populations was low (most pairwise F(ST) values < 0.03), and an overall test for isolation by distance was not significant. CONCLUSIONS: Although proportions of mixed genotype infections varied with endemicity as expected, population genetic structure was similar across the diverse sites. Very substantial reduction in transmission would be needed to cause fragmented or epidemic sub-structure in this region.

2011

Mwacharo, JM, Bjørnstad G, Mobegi V, Nomura K, Hanada H, Amano T, Jianlin H, Hanotte O.  2011.  Mitochondrial DNA reveals multiple introductions of domestic chicken in East Africa., 2011 Feb. Molecular phylogenetics and evolution. 58(2):374-82. Abstract

Chicken were possibly domesticated in South and Southeast Asia. They occur ubiquitously in East Africa where they show extensive phenotypic diversity. They appeared in the region relatively late, with the first undisputed evidence of domestic chicken in Sudan, around ~ 700 BC. We reveal through a detailed analysis of mitochondrial DNA D-loop sequence diversity of 512 domestic village chickens, from four East African countries (Kenya, Ethiopia, Sudan, Uganda), the presence of at least five distinct mitochondrial DNA haplogroups. Phylogeographic analyses and inclusion of reference sequences from Asia allow us to address the origin, ways of introduction and dispersion of each haplogroup. The results indicate a likely Indian subcontinent origin for the commonest haplogroup (D) and a maritime introduction for the next commonest one (A) from Southeast and/or East Asia. Recent introgression of commercial haplotypes into the gene pool of village chickens might explain the rare presence of two haplogroups (B and C) while the origin of the last haplogroup (E) remains unclear being currently observed only outside the African continent in the inland Yunnan Province of China. Our findings not only support ancient historical maritime and terrestrial contacts between Asia and East Africa, but also indicate the presence of large maternal genetic diversity in the region which could potentially support genetic improvement programmes.

2010

Revay, T, Bodzsar N, Mobegi VE, Hanotte O, Hidas A.  2010.  Origin of Hungarian indigenous chicken breeds inferred from mitochondrial {DNA} D-loop sequences, oct. Anim. Genet.. 41:548–550., Number 5: Wiley Abstract

In this study, we assessed the maternal origin of six Hungarian indigenous chicken breeds using mitochondrial DNA information. Sequences of Hungarian chickens were compared with the D-loop chicken sequences annotated in the GenBank and to nine previously described reference haplotypes representing the main haplogroups of chicken. The first 530 bases of the D-loop region were sequenced in 74 chickens of nine populations. Eleven haplotypes (HIC1-HIC11) were observed from 17 variable sites. Three sequences (HIC3,HIC8 and HIC9) of our chickens were found as unique to Hungary when searched against the NCBI GenBank database. Hungarian domestic chicken mtDNA sequences could be assigned into three clades and probably two maternal lineages. Results indicated that 86%of the Hungarian haplotypes are related to the reference sequence that likely originated from the Indian subcontinent, while the minor part of our sequences presumably derive from South East Asia, China and Japan.

AO, A, VA M, JM M, Jianlin H, BM O, RA A, LO I, BO M, O A, G B, H J, O H.  2010.  Lack of phylogeographic structure in Nigerian village chickens revealed by mitochondrial DNA D-loop sequence analysis. International Journal of Poultry Science. 9:503–507., Number 5 Abstract

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2008

Gongora, J, Rawlence NJ, Mobegi VA, Jianlin H, Alcalde JA, Matus JT, Hanotte O, Moran C, Austin JJ, Ulm S, Anderson AJ, Larson G, Cooper A.  2008.  Indo-European and Asian origins for Chilean and Pacific chickens revealed by mtDNA., 2008 Jul 29. Proceedings of the National Academy of Sciences of the United States of America. 105(30):10308-13. Abstract

European chickens were introduced into the American continents by the Spanish after their arrival in the 15th century. However, there is ongoing debate as to the presence of pre-Columbian chickens among Amerindians in South America, particularly in relation to Chilean breeds such as the Araucana and Passion Fowl. To understand the origin of these populations, we have generated partial mitochondrial DNA control region sequences from 41 native Chilean specimens and compared them with a previously generated database of approximately 1,000 domestic chicken sequences from across the world as well as published Chilean and Polynesian ancient DNA sequences. The modern Chilean sequences cluster closely with haplotypes predominantly distributed among European, Indian subcontinental, and Southeast Asian chickens, consistent with a European genetic origin. A published, apparently pre-Columbian, Chilean specimen and six pre-European Polynesian specimens also cluster with the same European/Indian subcontinental/Southeast Asian sequences, providing no support for a Polynesian introduction of chickens to South America. In contrast, sequences from two archaeological sites on Easter Island group with an uncommon haplogroup from Indonesia, Japan, and the Philippines [corrected] and may represent a genetic signature of an early Polynesian dispersal. Modeling of the potential marine carbon contribution to the Chilean archaeological specimen casts further doubt on claims for pre-Columbian chickens, and definitive proof will require further analyses of ancient DNA sequences and radiocarbon and stable isotope data from archaeological excavations within both Chile and Polynesia.

Razafindraibe, H, Mobegi VA, Ommeh SC, Rakotondravao ML, Bjørnstad G, Hanotte O, Jianlin H.  2008.  Mitochondrial DNA origin of indigenous malagasy chicken., 2008 Dec. Annals of the New York Academy of Sciences. 1149:77-9. Abstract

We report the mitochondrial DNA (mtDNA) characterization of 77 indigenous chickens (fighting and meat birds) from Madagascar, using DNA sequences of the first hypervariable segment of the D-loop. Comparison with reference samples from the African continent and Asia revealed two mtDNA haplogroups, suggesting a dual geographic and genetic origin for the indigenous Malagasy chickens. The most common haplogroup was present in 65 individuals of the two types; it is likely of Indonesian origin. The second haplogroup was observed in 12 fighting birds and meat chickens; it could be of African continental origin and/or the result of recent introgression with commercial lines. We further studied a G/A single nucleotide polymorphism at nucleotide position 1892 bp of the coding sequence of the Mx gene that is reported to be one of the candidate susceptible/resistant genes to viral infection in chicken. Our results indicate the "susceptible" allele G is the most common with frequencies of 65% and 70% in Malagasy fighting and meat chickens, respectively. However, the allelic frequency difference between the two types of chickens is not significant (P > 0.05). These results are discussed in light of our current linguistic and archaeological knowledge on the origin of indigenous Malagasy chickens.

2006

Mobegi, VA.  2006.  Genetic characterization of African chicken using mitochondrial DNA D-loop sequences. , Nairobi: University of Nairobi
Mobegi, AV, Rege JEO, Nyamu AM, Sendalo D, others.  2006.  Mitochondrial DNA D-loop sequences reveal the genetic diversity of African chicken.. The role of biotechnology in animal agriculture to address poverty in Africa: opportunities and challenges. Proceedings of the 4th All African Conference on Animal Agriculture and the 31st Annual Meeting of the Tanzania Society for Animal Production (TSAP. :293–298.: All Africa Society for Animal Production (AASAP) Abstract
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