scholarly journals Genetic polymorphism and natural selection of circumsporozoite surface protein in Plasmodium falciparum field isolates from Myanmar

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Hương Giang Lê ◽  
Jung-Mi Kang ◽  
Mya Moe ◽  
Hojong Jun ◽  
Thị Lam Thái ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Genetic Polymorphism ◽  
Surface Protein ◽  
Field Isolates ◽  
Selection Of

scholarly journals Genetic polymorphism of Plasmodium falciparum circumsporozoite protein (PfCSP) and mismatches against RTS, S/AS01 malaria vaccine observed on Bioko Island, Equatorial Guinea and globally

2020 ◽  
Author(s):  
Hui-Ying Huang ◽  
Xue-Yan Liang ◽  
Li-Yun Lin ◽  
Jiang-Tao Chen ◽  
Carlos Salas Ehapo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Genetic Polymorphism ◽  
Genetic Polymorphisms ◽  
Vaccine Efficacy ◽  
Malaria Vaccine ◽  
Repetitive Sequences ◽  
Circumsporozoite Protein ◽  
Bioko Island ◽  
Selection Of

Abstract Backgroud RTS, S/AS01 is a Plasmodium falciparum circumsporozoite protein ( PfCSP ) based anti-malaria vaccine, but various genetic polymorphisms of PfCSP among global P. falciparum population could lead to mismatch against the PfCSP - based vaccine and reduce vaccine efficacy. This study aimed to investigate the genetic polymorphisms and natural selection of PfCSP in Bioko as well as global P. falciparum population. Methods From January 2011 to December 2018, 148 blood samples were collected from P. falciparum infected Bioko patients and 96 monoclonal sequences of them were successfully acquired and analyzed with 2200 global PfCSP sequences mined from MalariaGEN Pf3k Database and NCBI. Results In Bioko, the N-terminus of PfCSP showed limited genetic variations and the numbers of repetitive sequences (NANP/NVDP) were mainly found as 40 (35%) and 41 (34%) in central region. Most polymorphic characters were found in Th2R/Th3R region, where natural selection (p>0.05) and recombination occurred. The overall pattern of Bioko PfCSP gene had no obvious deviation from African mainland PfCSP (Fst=0.00878, p<0.05). The comparative analysis of Bioko and global PfCSP displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p<0.05). The global PfCSP C-terminal sequences were clustered into 138 different haplotypes (H_1 to H_138). Only 3.35% of sequences matched 3D7 vaccine strain haplotype (H_1). Conclusions The genetic polymorphism phenomena of PfCSP were found universal. The overall vaccine efficacy might be influenced by the low proportion of vaccine-matched isolates in global parasites population. Genetic polymorphism and geographical characteristics should be considered for future improvement of RTS, S/AS01.

scholarly journals Genetic polymorphism of merozoite surface protein-3 in Myanmar Plasmodium falciparum field isolates

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Hương Giang Lê ◽  
Thị Lam Thái ◽  
Jung-Mi Kang ◽  
Jinyoung Lee ◽  
Mya Moe ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Polymorphism ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Field Isolates

scholarly journals 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

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.

scholarly journals Genetic polymorphism of Merozoite Surface Protein-2 (MSP-2) in Plasmodium falciparum isolates from Pawe District, North West Ethiopia

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0177559 ◽  
Author(s):  
Hussein Mohammed ◽  
Moges Kassa ◽  
Ashenafi Assefa ◽  
Mekonnen Tadesse ◽  
Amha Kebede
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Polymorphism ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
North West ◽  
North West Ethiopia

α+-thalassemia protects African children from severe malaria

Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 2003-2006 ◽  
Author(s):  
Frank P. Mockenhaupt ◽  
Stephan Ehrhardt ◽  
Sabine Gellert ◽  
Rowland N. Otchwemah ◽  
Ekkehart Dietz ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Confidence Interval ◽  
Severe Malaria ◽  
High Frequency ◽  
Odds Ratio ◽  
Case Control Study ◽  
Case Control ◽  
Control Study ◽  
Selection Of

Abstract The high frequency of α+-thalassemia in malaria-endemic regions may reflect natural selection due to protection from potentially fatal severe malaria. In Africa, bearing 90% of global malaria morbidity and mortality, this has not yet been observed. We tested this hypothesis in an unmatched case-control study among 301 Ghanaian children with severe malaria and 2107 controls (62% parasitemic). In control children, α+-thalassemia affected neither prevalence nor density of Plasmodium falciparum. However, heterozygous α+-thalassemia was observed in 32.6% of controls but in only 26.2% of cases (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.56-0.98). Protection against severe malaria was found to be pronounced comparing severe malaria patients with parasitemic controls (adjusted OR in children &lt; 5 years of age, 0.52; 95% CI, 0.34-0.78) and to wane with age. No protective effect was discernible for homozygous children. Our findings provide evidence for natural selection of α+-thalassemia in Africa due to protection from severe malaria.

scholarly journals Genetic polymorphism and natural selection of circumsporozoite protein in Myanmar Plasmodium vivax

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Tuấn Cường Võ ◽  
Hương Giang Lê ◽  
Jung-Mi Kang ◽  
Mya Moe ◽  
Haung Naw ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Plasmodium Vivax ◽  
Surface Protein ◽  
Genetic Profile ◽  
Repeat Region ◽  
Polymorphic Pattern ◽  
High Level ◽  
Global Population ◽  
Selection Of

Abstract Background Circumsporozoite surface protein (CSP) of malaria parasites has been recognized as one of the leading vaccine candidates. Clinical trials of vaccines for vivax malaria incorporating Plasmodium vivax CSP (PvCSP) have demonstrated their effectiveness in preventing malaria, at least in part. However, genetic diversity of pvcsp in the natural population remains a major concern. Methods A total of 171 blood samples collected from patients infected with Plasmodium vivax in Myanmar were analysed in this study. The pvcsp was amplified by polymerase chain reaction, followed by cloning and sequencing. Polymorphic characteristics and natural selection of pvcsp population in Myanmar were analysed using DNASTAR, MEGA6 and DnaSP programs. The polymorphic pattern and natural selection of publicly accessible global pvcsp sequences were also comparatively analysed. Results Myanmar pvcsp sequences were divided into two subtypes VK210 and VK247 comprising 143 and 28 sequences, respectively. The VK210 subtypes showed higher levels of genetic diversity and polymorphism than the VK247 subtypes. The N-terminal non-repeat region of pvcsp displayed limited genetic variations in the global population. Different patterns of octapeptide insertion (ANKKAEDA in VK210 and ANKKAGDA in VK247) and tetrapeptide repeat motif (GGNA) were identified in the C-terminal region of global pvcsp population. Meanwhile, the central repeat region (CRR) of Myanmar and global pvcsp, both in VK210 and VK247 variants, was highly polymorphic. The high level of genetic diversity in the CRR has been attributed to the different numbers, types and combinations of peptide repeat motifs (PRMs). Interestingly, 27 and 5 novel PRMs were found in Myanmar VK210 and VK247 variants, respectively. Conclusion Comparative analysis of the global pvcsp population suggests a complex genetic profile of pvcsp in the global population. These results widen understanding of the genetic make-up of pvcsp in the global P. vivax population and provide valuable information for the development of a vaccine based on PvCSP.

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