scholarly journals Genetic diversity of circumsporozoite protein in Plasmodium knowlesi isolates from Malaysian Borneo and Peninsular Malaysia

2020 ◽  
Author(s):  
Eric Tzyy Jiann Chong ◽  
Joveen Wan Fen Neoh ◽  
Tiek Ying Lau ◽  
Yvonne Ai-Lian Lim ◽  
Hwa Chia Chai ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Knowlesi ◽  
Polymerase Chain Reaction Amplification ◽  
Population Expansion ◽  
Purifying Selection ◽  
Peninsular Malaysia ◽  
Circumsporozoite Protein ◽  
Malaria Vaccines ◽  
Reaction Amplification ◽  
Malaysian Borneo

Abstract Background Understanding the genetic diversity of candidate genes for malaria vaccines such as circumsporozoite protein (csp) may enhance the development of vaccines for treating Plasmodium knowlesi. Hence, the aim of this study is to investigate the genetic diversity of non-repeat regions of csp in P. knowlesi from Malaysian Borneo and Peninsular Malaysia. Methods A total of 46 csp genes were subjected to polymerase chain reaction amplification. The genes were obtained from P. knowlesi isolates collected from different divisions of Sabah, Malaysian Borneo, and Peninsular Malaysia. The targeted gene fragments were cloned into a commercial vector and sequenced, and a phylogenetic tree was constructed while incorporating 168 csp sequences retrieved from the GenBank database. The genetic diversity and natural evolution of the csp sequences were analysed using MEGA6 and DnaSP ver. 5.10.01. A genealogical network of the csp haplotypes was generated using NETWORK ver. 4.6.1.3. Results The phylogenetic analysis revealed indistinguishable clusters of P. knowlesi isolates across different geographic regions, including Malaysian Borneo and Peninsular Malaysia. Nucleotide analysis showed that the csp non-repeat regions of zoonotic P. knowlesi isolates obtained in this study underwent purifying selection with population expansion, which was supported by extensive haplotype sharing observed between humans and macaques. Conclusions The csp non-repeat regions are relatively conserved and cannot be used to distinguish P. knowlesi isolates between Malaysian Borneo and Peninsular Malaysia. Novel variations were observed in the C-terminal non-repeat region of csp. The data obtained could be beneficial for the design and development of vaccines to treat P. knowlesi.

scholarly journals Genetic diversity of circumsporozoite protein in Plasmodium knowlesi isolates from Malaysian Borneo and Peninsular Malaysia

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Eric Tzyy Jiann Chong ◽  
Joveen Wan Fen Neoh ◽  
Tiek Ying Lau ◽  
Yvonne Ai-Lian Lim ◽  
Hwa Chia Chai ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Knowlesi ◽  
Polymerase Chain Reaction Amplification ◽  
Population Expansion ◽  
Purifying Selection ◽  
Peninsular Malaysia ◽  
Circumsporozoite Protein ◽  
Repeat Region ◽  
Malaria Vaccines ◽  
Malaysian Borneo

Abstract Background Understanding the genetic diversity of candidate genes for malaria vaccines such as circumsporozoite protein (csp) may enhance the development of vaccines for treating Plasmodium knowlesi. Hence, the aim of this study is to investigate the genetic diversity of non-repeat regions of csp in P. knowlesi from Malaysian Borneo and Peninsular Malaysia. Methods A total of 46 csp genes were subjected to polymerase chain reaction amplification. The genes were obtained from P. knowlesi isolates collected from different divisions of Sabah, Malaysian Borneo, and Peninsular Malaysia. The targeted gene fragments were cloned into a commercial vector and sequenced, and a phylogenetic tree was constructed while incorporating 168 csp sequences retrieved from the GenBank database. The genetic diversity and natural evolution of the csp sequences were analysed using MEGA6 and DnaSP ver. 5.10.01. A genealogical network of the csp haplotypes was generated using NETWORK ver. 4.6.1.3. Results The phylogenetic analysis revealed indistinguishable clusters of P. knowlesi isolates across different geographic regions, including Malaysian Borneo and Peninsular Malaysia. Nucleotide analysis showed that the csp non-repeat regions of zoonotic P. knowlesi isolates obtained in this study underwent purifying selection with population expansion, which was supported by extensive haplotype sharing observed between humans and macaques. Novel variations were observed in the C-terminal non-repeat region of csp. Conclusions The csp non-repeat regions are relatively conserved and there is no distinct cluster of P. knowlesi isolates from Malaysian Borneo and Peninsular Malaysia. Distinctive variation data obtained in the C-terminal non-repeat region of csp could be beneficial for the design and development of vaccines to treat P. knowlesi.

scholarly journals Genetic diversity of circumsporozoite protein in Plasmodium knowlesi isolates from Malaysian Borneo and Peninsular Malaysia

2020 ◽  
Author(s):  
Eric Tzyy Jiann Chong ◽  
Joveen Wan Fen Neoh ◽  
Tiek Ying Lau ◽  
Yvonne Ai-Lian Lim ◽  
Hwa Chia Chai ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Knowlesi ◽  
Polymerase Chain Reaction Amplification ◽  
Population Expansion ◽  
Purifying Selection ◽  
Peninsular Malaysia ◽  
Circumsporozoite Protein ◽  
Repeat Region ◽  
Malaria Vaccines ◽  
Malaysian Borneo

Abstract Background: Understanding the genetic diversity of candidate genes for malaria vaccines such as circumsporozoite protein (csp) may enhance the development of vaccines for treating Plasmodium knowlesi. Hence, the aim of this study is to investigate the genetic diversity of non-repeat regions of csp in P. knowlesi from Malaysian Borneo and Peninsular Malaysia. Methods: A total of 46 csp genes were subjected to polymerase chain reaction amplification. The genes were obtained from P. knowlesi isolates collected from different divisions of Sabah, Malaysian Borneo, and Peninsular Malaysia. The targeted gene fragments were cloned into a commercial vector and sequenced, and a phylogenetic tree was constructed while incorporating 168 csp sequences retrieved from the GenBank database. The genetic diversity and natural evolution of the csp sequences were analysed using MEGA6 and DnaSP ver. 5.10.01. A genealogical network of the csp haplotypes was generated using NETWORK ver. 4.6.1.3. Results: The phylogenetic analysis revealed indistinguishable clusters of P. knowlesi isolates across different geographic regions, including Malaysian Borneo and Peninsular Malaysia. Nucleotide analysis showed that the csp non-repeat regions of zoonotic P. knowlesi isolates obtained in this study underwent purifying selection with population expansion, which was supported by extensive haplotype sharing observed between humans and macaques. Novel variations were observed in the C-terminal non-repeat region of csp. Conclusions: The csp non-repeat regions are relatively conserved and there is no distinct cluster of P. knowlesi isolates from Malaysian Borneo and Peninsular Malaysia. Distinctive variation data obtained in the C-terminal non-repeat region of csp could be beneficial for the design and development of vaccines to treat P. knowlesi.

scholarly journals Identification, Mapping, and Genetic Diversity of Novel Conserved Cross-Species Epitopes of RhopH2 in Plasmodium knowlesi With Plasmodium vivax

2022 ◽  
Vol 11 ◽  
Author(s):  
Md Atique Ahmed ◽  
Gauspasha Yusuf Deshmukh ◽  
Rehan Haider Zaidi ◽  
Ahmed Saif ◽  
Mohammed Abdulrahman Alshahrani ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Plasmodium Knowlesi ◽  
Epitope Prediction ◽  
Purifying Selection ◽  
Peninsular Malaysia ◽  
Health Concern ◽  
Clinical Samples

Malaria is a major public health concern, and any tangible intervention during the pre-elimination phase can result in a significant reduction in infection rates. Recent studies have reported that antigens producing cross-protective immunity can play an important role as vaccines and halt malaria transmission in different endemic regions. In this study, we studied the genetic diversity, natural selection, and discovered novel conserved epitopes of a high molecular weight rhoptry protein 2 (RhopH2) in clinical samples of Plasmodium knowlesi and Plasmodium vivax cross-protective domains, which has been proven to produce cross-protective immunity in both species. We found low levels of nucleotide diversity (P. knowlesi; π ~ 0.0093, SNPs = 49 and P. vivax π ~ 0.0014, SNPs = 23) in P. knowlesi (n = 40) and P. vivax (n = 65) samples in the PkRhopH2 cross-protective domain. Strong purifying selection was observed for both species (P. knowlesi; dS - dN = 2.41, p < 0.009, P. vivax; dS - dN = 1.58, p < 0.050). In silico epitope prediction in P. knowlesi identified 10 potential epitopes, of which 7 epitopes were 100% conserved within clinical samples. Of these epitopes, an epitope with 10 amino acids (QNSKHFKKEK) was found to be fully conserved within all P. knowlesi and P. vivax clinical samples and 80%–90% conservation within simian malaria ortholog species, i.e., P. coatneyi and P. cynomolgi. Phylogenetic analysis of the PkRhopH2 cross-protective domain showed geographical clustering, and three subpopulations of P. knowlesi were identified of which two subpopulations originated from Sarawak, Malaysian Borneo, and one comprised only the laboratory lines from Peninsular Malaysia. This study suggests that RhopH2 could be an excellent target for cross-protective vaccine development with potential for outwitting strain as well as species-specific immunity. However, more detailed studies on genetic diversity using more clinical samples from both species as well as the functional role of antibodies specific to the novel conserved epitope identified in this study can be explored for protection against infection.

scholarly journals Population genetic analysis of the Plasmodium falciparum circumsporozoite protein in two distinct ecological regions in Ghana

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Elikplim A. Amegashie ◽  
Lucas Amenga-Etego ◽  
Courage Adobor ◽  
Peter Ogoti ◽  
Kevin Mbogo ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Sequence Data ◽  
Balancing Selection ◽  
Population Expansion ◽  
Circumsporozoite Protein ◽  
Cape Coast ◽  
Population Genetic Analysis ◽  
Coastal Belt ◽  
Tajima’S D

Abstract Background Extensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/AS01 vaccine. The transmission intensity and rates of recombination within and between populations influence the extent of its genetic diversity. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria-endemic areas such as Ghana. Methods Pfcsp sequences were retrieved from the Illumina-generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6–59 months presenting with clinical malaria at health facilities in Cape Coast (in the coastal belt) and Navrongo (Guinea savannah region), respectively, in Ghana. The sequences were mapped onto the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data filtering and quality checks to remove missing data, 220 sequences were retained and analysed for the allele frequency spectrum, genetic diversity both within the host and between populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geographically distinct locations in Ghana. Results Pfcsp showed extensive diversity at the two sites, with the higher transmission site, Navrongo, exhibiting higher within-host and population-level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences, respectively. Between 1 and 6 amino acid variations were observed in the TH2R and TH3R epitope regions of PfCSP. Tajima’s D was negatively skewed, especially for the population from Cape Coast, given the expected historical population expansion. In contrast, a positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immuno-dominant TH2R and TH3R vaccine epitopes. Conclusion The low frequencies of the Pfcsp vaccine haplotype in the analysed populations indicate a need for additional molecular and immuno-epidemiological studies with broader temporal and geographic sampling in endemic populations targeted for RTS,S application. These results have implications for the efficacy of the vaccine in Ghana and will inform the choice of alleles to be included in future multivalent or chimeric vaccines.

scholarly journals Short Communication: Genetic diversity of scalloped hammerhead sharks (Sphyrna lewini) landed in Muncar Fishing Port, Banyuwangi

2019 ◽  
Vol 20 (4) ◽  
pp. 1154-1159 ◽  
Author(s):  
FAQIH AKBAR ALGHOZALI ◽  
DIAH PERMATA WIJAYANTI ◽  
AGUS SABDONO
Keyword(s):  
Genetic Diversity ◽  
Short Communication ◽  
Polymerase Chain Reaction Amplification ◽  
Haplotype Diversity ◽  
Population Expansion ◽  
Fishing Ground ◽  
Sphyrna Lewini ◽  
Scalloped Hammerhead ◽  
Hammerhead Sharks ◽  
Longline Fisheries

Abstract. Alghozali FA, Wijayanti DP, Sabdono A. 2019. Short Communication: Genetic diversity of scalloped hammerhead sharks (Sphyrna lewini) landed in Muncar Fishing Port, Banyuwangi. Biodiversitas 20: 1154-1159. The majority of sharks caught in Indonesian fisheries were bycatch products from the tuna longline fisheries, but some regions in Indonesia fish the sharks as their main target. One of these regions is located in Muncar, Banyuwangi, which fishes the endangered Scalloped Hammerhead sharks (Sphyrna lewini) as target species. This research aimed to study the genetic diversity of the endangered Scalloped Hammerhead sharks landed in Muncar Fishing Port, Banyuwangi. Genetic analysis was done through PCR (Polymerase Chain Reaction) amplification and sequencing of the mitochondrial DNA COI (Cytochrome Oxidase subunit I) gene. Out of the 37 samples collected, 30 were successfully amplified and sequenced.The results showed moderate haplotype diversity (Hd: 0,582 ± 0,079) and low nucleotide diversity (π: 0,00392± 0,0024) with five haplotypes (h) and 26 polymorphic sites (S). Tajima’s D neutrality model values indicated a population expansion event. Two different clades were determined through phylogenetic analysis and by GenBank sequences comparison. These results provided basic information and present status of the Scalloped Hammerhead sharks population genetically within the fishing ground (Makassar Strait-Kangean Islands).

scholarly journals Population Genetic Analysis of Plasmodium falciparum Circumsporozoite Protein in Two Distinct Ecological Regions in Ghana

2020 ◽  
Author(s):  
Elikplim A Amegashie ◽  
Lucas Amenga-Etego ◽  
Courage Adobor ◽  
Peter Ogoti ◽  
Kevin Mbogo ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Sequence Data ◽  
Balancing Selection ◽  
Population Expansion ◽  
Circumsporozoite Protein ◽  
Cape Coast ◽  
Population Genetic Analysis ◽  
Coastal Belt ◽  
Tajima’S D

Abstract Background Extensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/AS01 vaccine. The transmission intensity and rates of recombination within and between populations influence the extent of its genetic diversity. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria-endemic areas such as Ghana. Methods Pfcsp sequences were retrieved from the Illumina-generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6-59 months presenting with clinical malaria at health facilities in Cape Coast (in the coastal belt) and Navrongo (Guinea savannah region), respectively, in Ghana. The sequences were mapped onto the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data filtering and quality checks to remove missing data, 220 sequences were retained and analysed for the allele frequency spectrum, genetic diversity both within the host and between populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geographically distinct locations in Ghana. Results Pfcsp showed extensive diversity at the two sites, with the higher transmission site, Navrongo, exhibiting higher within-host and population-level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences, respectively. Between 1 and 6 amino acid variations were observed in the TH2R and TH3R epitope regions of PfCSP. Tajima’s D was negatively skewed, especially for the population from Cape Coast, given the expected historical population expansion. In contrast, a positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immuno-dominant TH2R and TH3R vaccine epitopes. Conclusion The low frequencies of the Pfcsp vaccine haplotype in the analysed populations indicate a need for additional molecular and immuno-epidemiological studies with broader temporal and geographic sampling in endemic populations targeted for RTS,S application. These results have implications for the efficacy of the vaccine in Ghana and will inform the choice of alleles to be included in future multivalent or chimeric vaccines.

scholarly journals Population Genetic Analysis of Plasmodium Falciparum Circumsporozoite Protein in Two Distinct Ecological Regions in Ghana

2020 ◽  
Author(s):  
Elikplim A Amegashie ◽  
Lucas Amenga-Etego ◽  
Courage Adobor ◽  
Peter Ogoti ◽  
Kevin Mbogo ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Sequence Data ◽  
Balancing Selection ◽  
Population Expansion ◽  
Circumsporozoite Protein ◽  
Cape Coast ◽  
Population Genetic Analysis ◽  
Coastal Belt ◽  
Tajima’S D

Abstract BackgroundExtensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/ASO1 vaccine. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria endemic areas such as Ghana. MethodsPfcsp sequences were retrieved from Illumina generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6-59 months with clinical malaria presenting at health facilities in Cape Coast (on the coastal belt) and Navrongo (Guinea savannah region) respectively in Ghana. The sequences were mapped to the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data filtering and quality checks to remove missing data, 220 sequences were retained and analyzed for allele frequency spectrum, genetic diversity both within host and between the populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geographically distinct locations in Ghana. ResultsPfcsp was extensively diverse at the two sites with higher transmission site, Navrongo, recording both higher within host and population level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences respectively. Amino acid variations ranging between 1 and 6 were observed in the TH2R and TH3R epitope regions of the PfCSP. Tajima’s D was negatively skewed especially for the population from Cape Coast given expected historical population expansion. On the contrary, positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immuno-dominant TH2R and TH3R vaccine epitopes. ConclusionThe low frequencies of Pfcsp vaccine haplotype in the populations analyzed calls for additional molecular and immuno-epidemiological studies with temporal and wider geographic sampling in endemic populations targeted for RTS,S application. These results have implications on the efficacy of the vaccine in Ghana and will inform the choice of alleles to include in future multivalent or chimeric vaccines.

scholarly journals Genetic diversity of Plasmodium knowlesi among human and long-tailed macaque populations in Peninsular Malaysia: The utility of microsatellite markers

2019 ◽  
Vol 75 ◽  
pp. 103952
Author(s):  
Afiqah Saleh Huddin ◽  
NoorAzian Md Yusuf ◽  
Mohd Ridzuan Mohd Abd Razak ◽  
Nurhainis Ogu Salim ◽  
Shamilah Hisam
Keyword(s):  
Genetic Diversity ◽  
Microsatellite Markers ◽  
Plasmodium Knowlesi ◽  
Peninsular Malaysia
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