Plasmodium falciparum mitochondrial genetic diversity exhibits isolation-by-distance patterns supporting a sub-Saharan African origin

Glutamate-rich protein is a Plasmodium falciparum ( Pf) antigen found in all stages of the parasite and has been reported to induce clinical immunity. The R0 and R2 regions have been found to exhibit a high degree of conservation, therefore serving as a good vaccine design material. We assayed the genetic diversity of Pf glurp genes in the R0 and R2 regions, as well as evaluated the role of seasonality on allelic frequency. A total of 402 genomic DNA samples, extracted from filter paper blood samples, were screened by nested polymerase chain reaction (PCR) analysis of Pf glurp R0 and R2 regions, in addition to fragment analysis of the polymorphic regions to identify allelic diversity of the parasite population. We found an extensive heterogeneity in the R2 region in general, and this heterogeneity is seasonally dependent, indicative of region plasticity. The R0 region displayed genetic conservation, as expected. We conclude that positive genotyping results with glurp R0 region should be seen as indicative of an active Pf infection, requiring adequate treatment. In addition, we advocate extending the possibility that an R0 region genotypic positivity could serve as diagnostic tool, thereby reducing cases of untreated or poorly treated infection, contributory to recrudescence or treatment failure.

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Faculty Opinions recommendation of Relationship between Plasmodium falciparum malaria prevalence, genetic diversity and endemic Burkitt lymphoma in Malawi.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718242317.793542339 ◽

2018 ◽

Author(s):

Toshihiro Horii ◽

Nirianne Palacpac

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Falciparum Malaria ◽

Burkitt Lymphoma ◽

Plasmodium Falciparum Malaria ◽

Malaria Prevalence

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Genetic diversity and population structure of Plasmodium falciparum in Nigeria: insights from microsatellite loci analysis

Malaria Journal ◽

10.1186/s12936-021-03734-x ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Fehintola V. Ajogbasile ◽

Adeyemi T. Kayode ◽

Paul E. Oluniyi ◽

Kazeem O. Akano ◽

Jessica N. Uwanibe ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Population Structure ◽

Microsatellite Loci ◽

Control Strategies ◽

Population Diversity ◽

Parasite Population ◽

Nested Polymerase Chain Reaction ◽

Public Health Burden ◽

Genetic Diversity And Structure

Abstract Background Malaria remains a public health burden especially in Nigeria. To develop new malaria control and elimination strategies or refine existing ones, understanding parasite population diversity and transmission patterns is crucial. Methods In this study, characterization of the parasite diversity and structure of Plasmodium falciparum isolates from 633 dried blood spot samples in Nigeria was carried out using 12 microsatellite loci of P. falciparum. These microsatellite loci were amplified via semi-nested polymerase chain reaction (PCR) and fragments were analysed using population genetic tools. Results Estimates of parasite genetic diversity, such as mean number of different alleles (13.52), effective alleles (7.13), allelic richness (11.15) and expected heterozygosity (0.804), were high. Overall linkage disequilibrium was weak (0.006, P < 0.001). Parasite population structure was low (Fst: 0.008–0.105, AMOVA: 0.039). Conclusion The high level of parasite genetic diversity and low population structuring in this study suggests that parasite populations circulating in Nigeria are homogenous. However, higher resolution methods, such as the 24 SNP barcode and whole genome sequencing, may capture more specific parasite genetic signatures circulating in the country. The results obtained can be used as a baseline for parasite genetic diversity and structure, aiding in the formulation of appropriate therapeutic and control strategies in Nigeria.

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Genetic diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum on Bioko Island, Equatorial Guinea and global comparative analysis

Malaria Journal ◽

10.1186/s12936-021-03664-8 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Li-Yun Lin ◽

Hui-Ying Huang ◽

Xue-Yan Liang ◽

Dong-De Xie ◽

Jiang-Tao Chen ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Natural Selection ◽

Protein Structure ◽

Transmembrane Protein ◽

Fixation Index ◽

Bioko Island ◽

Adhesive Protein ◽

Trap Gene ◽

Selection Of

Abstract Background Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. Methods 153 blood spot samples from Bioko malaria patients were collected during 2016–2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. Results A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN–dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. Conclusions Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.

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Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia

Malaria Journal ◽

10.1186/s12936-020-03467-3 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Ommer Mohammed Dafalla ◽

Mohammed Alzahrani ◽

Ahmed Sahli ◽

Mohammed Abdulla Al Helal ◽

Mohammad Mohammad Alhazmi ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Saudi Arabia ◽

Parasite Clearance ◽

Sub Saharan Africa ◽

Local Alignment ◽

Nucleotide Polymorphisms ◽

Gene Encoding ◽

Synonymous Mutations ◽

Search Tool ◽

Sub Saharan

Abstract Background Artemisinin-based combination therapy (ACT) is recommended at the initial phase for treatment of Plasmodium falciparum, to reduce morbidity and mortality in all countries where malaria is endemic. Polymorphism in portions of P. falciparum gene encoding kelch (K13)-propeller domains is associated with delayed parasite clearance after ACT. Of about 124 different non-synonymous mutations, 46 have been identified in Southeast Asia (SEA), 62 in sub-Saharan Africa (SSA) and 16 in both the regions. This is the first study designed to analyse the prevalence of polymorphism in the P. falciparum k13-propeller domain in the Jazan region of southwest Saudi Arabia, where malaria is endemic. Methods One-hundred and forty P. falciparum samples were collected from Jazan region of southwest Saudi Arabia at three different times: 20 samples in 2011, 40 samples in 2016 and 80 samples in 2020 after the implementation of ACT. Plasmodium falciparum kelch13 (k13) gene DNA was extracted, amplified, sequenced, and analysed using a basic local alignment search tool (BLAST). Results This study obtained 51 non-synonymous (NS) mutations in three time groups, divided as follows: 6 single nucleotide polymorphisms (SNPs) ‘11.8%’ in samples collected in 2011 only, 3 (5.9%) in 2011and 2016, 5 (9.8%) in 2011 and 2020, 5 (9.8%) in 2016 only, 8 (15.7%) in 2016 and 2020, 14 (27.5%) in 2020 and 10 (19.6%) in all the groups. The BLAST revealed that the 2011 isolates were genetically closer to African isolates (53.3%) than Asian ones (46.7%). Interestingly, this proportion changed completely in 2020, to become closer to Asian isolates (81.6%) than to African ones (18.4%). Conclusions Despite the diversity of the identified mutations in the k13-propeller gene, these data did not report widespread artemisinin-resistant polymorphisms in the Jazan region where these samples were collected. Such a process would be expected to increase frequencies of mutations associated with the resistance of ACT.

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Genetic Diversity of CD14 Promoter Gene Polymorphism (rs2569190) is Associated With Regulation of Malaria Parasitemia and Susceptibility to Plasmodium falciparum Infection

Infectious Diseases Research and Treatment ◽

10.1177/1178633617726781 ◽

2017 ◽

Vol 10 ◽

pp. 117863361772678 ◽

Cited By ~ 6

Author(s):

Olusola Ojurongbe ◽

Roland I Funwei ◽

Tara J Snyder ◽

Najihah Aziz ◽

Yi Li ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Plasmodium Falciparum Malaria ◽

Cell Types ◽

Infected Group ◽

Genotypic Frequency ◽

Experimental Cerebral Malaria ◽

Asymptomatic Patients ◽

Mutant Variant ◽

Promoter Gene

CD14 is a multifunctional receptor expressed on many cell types and has been shown to mediate immune response resulting in the activation of an inflammatory cascade, with polymorphism of its promoter (rs2569190) found to be associated with susceptibility to several diseases. In malaria infection, the CD14 gene demonstrated a pathogenic profile in regulating experimental cerebral malaria, with reports of elevated levels of soluble CD14 in serum of patients but no definitive conclusion. We present a detailed analysis of genetic diversity of CD14 promoter gene (snp −159 C/T; rs2519190) polymorphism between a malaria-infected group and uninfected controls and its association with clinical parameters of disease. Genomic DNA samples obtained from 106 Plasmodium falciparum malaria–infected patients and 277 uninfected controls were elucidated with a polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. Our results show a significant diversity ( P = 3.32E−06) in the genotypic frequency (3.8% versus 22.4%) of the rs2569190 mutant variant between the malaria-infected group and controls, respectively. The mutant allele had the lowest frequency among the malaria-infected group demonstrating its necessity for infection. Mean parasitemia (parasites/μL of blood) was significantly regulated based on CD14 polymorphic profile (19 855 versus 37 041 versus 49 396 for homozygote mutants, heterozygotes, and homozygote wild type, respectively). Interestingly, we found no association between CD14 genetic variants with fever, age of patients, or anemia. How this affects disease severity between subregional and continental groups deserves further clarification, including extending these studies in a larger group and among severe and asymptomatic patients with malaria.

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