scholarly journals Efficacy of Artemisinin Base Combination Therapy and Genetic Diversity of Plasmodium falciparum from Uncomplicated Ma-laria Falciparum Patient in District of Pesawaran, Province of Lampung, Indonesia

2019 ◽  
Author(s):  
Jhons Fatriyadi SUWANDI ◽  
Widya ASMARA ◽  
Hari KUSNANTO ◽  
Din SYAFRUDDIN ◽  
Supargiyono SUPARGIYONO
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Variation ◽  
Falciparum Malaria ◽  
Health Centre ◽  
Sequencing Data ◽  
Single Nucleotide ◽  
Pfmdr1 Gene ◽  
Pcr Product ◽  
Nucleotide Mutation ◽  
Reverse Primer

Background: Malaria is an infectious disease caused by Plasmodium sp., that still prevalence in some part of Indonesia. District of Pesawaran is one of malaria endemic area in the Province of Lampung. The purpose of this study was to evaluate the efficacy of the ACT treatment in the District of Pesawaran Province of Lampung, Indonesia from Dec 2012 to Jul 2013 and the genetic variation of the Plasmodium falciparum also studied. Methods: This study was observational analytic study of falciparum malaria patients treated with ACT and primaquine (DHP-PQ and AAQ-PQ) at Hanura Primary Health Centre (Puskesmas). DNA isolation was done with QIAmp DNA Mini Kit. Amplification of PfMDR1, MSP1, and MSP2 genes was done with appropriate forward and reverse primer and procedures optimized first. PCR Product of PfMDR1 gene was prepared for sequencing. Data analysis was done with MEGA 6 software. Results: The results of this research are DHP-PQ effectiveness was still wellness among falciparum malaria patients in District of Pesawaran, Province of Lampung, Indonesia. There is Single-nucleotide mutation of N86Y of PfMDR1 gene. The dominant alleles found are MAD20 and 3D7 alleles with Multiplicity of Infection (MOI) are low. Conclusion: Therapy of DHP-PQ as an antimalarial falciparum in Pesawaran District, Lampung, Indonesia is still good. The genetic variation found was the SNP on the N86Y PfMDR1 gene, with dominant allele MAD20 and 3D7.

scholarly journals De novo mutations across 1,465 diverse genomes reveal novel mutational insights and reductions in the Amish founder population

2019 ◽  
Author(s):  
Michael D. Kessler ◽  
Douglas P. Loesch ◽  
James A. Perry ◽  
Nancy L. Heard-Costa ◽  
Brian E. Cade ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Mutation Rate ◽  
De Novo ◽  
Population Level ◽  
Mutation Rates ◽  
Founder Population ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Nucleotide Mutation ◽  
Rare Genetic Variation

Abstractde novo Mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) program, we directly estimate and analyze DNM counts, rates, and spectra from 1,465 trios across an array of diverse human populations. Using the resulting call set of 86,865 single nucleotide DNMs, we find a significant positive correlation between local recombination rate and local DNM rate, which together can explain up to 35.5% of the genome-wide variation in population level rare genetic variation from 41K unrelated TOPMed samples. While genome-wide heterozygosity does correlate weakly with DNM count, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, interestingly, we do find significantly fewer DNMs in Amish individuals compared with other Europeans, even after accounting for parental age and sequencing center. Specifically, we find significant reductions in the number of T→C mutations in the Amish, which seems to underpin their overall reduction in DNMs. Finally, we calculate near-zero estimates of narrow sense heritability (h2), which suggest that variation in DNM rate is significantly shaped by non-additive genetic effects and/or the environment, and that a less mutagenic environment may be responsible for the reduced DNM rate in the Amish.SignificanceHere we provide one of the largest and most diverse human de novo mutation (DNM) call sets to date, and use it to quantify the genome-wide relationship between local mutation rate and population-level rare genetic variation. While we demonstrate that the human single nucleotide mutation rate is similar across numerous human ancestries and populations, we also discover a reduced mutation rate in the Amish founder population, which shows that mutation rates can shift rapidly. Finally, we find that variation in mutation rates is not heritable, which suggests that the environment may influence mutation rates more significantly than previously realized.

scholarly journals Fibrinogen and C-Reactive Protein Significance in Children Infected by Plasmodium falciparum Species in Enugu, Enugu State, Nigeria

2021 ◽  
pp. 1-8
Author(s):  
Linda Nnenna Ogbonna ◽  
Silas Anayo Ufelle ◽  
Emmanuel Ifeanyi Obeagu ◽  
Pat Uzo Okpala ◽  
Bessie N. Esimai ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Parasite Density ◽  
Health Centre ◽  
Blood Film ◽  
University Teaching ◽  
Morbidity Rate ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Enugu State

Malaria accounts for a considerable mortality and morbidity rate with children bearing the greatest burden. The study investigated fibrinogen and C-reactive protein (CRP) value alterations in children infected by Plasmodium falciparum (P. falciparum) species. A case control study with a total of ninety-five microscopically confirmed P. falciparum malaria infected children and fifty apparently healthy age and gender matched controls from Enugu State University Teaching Hospital, Parklane, Wesley Specialist Hospital and Akpugo Community Health Centre, Enugu were recruited for the study. Fibrinogen level was determined by clauss clotting time method using sodium citrated plasma. Giemsa stained thick and thin blood film was used for parasite identification and calculation of parasite density. Serum CRP values was determined by immunoturbidimetric method. Fibrinogen levels were significantly increased (p < 0.05) in P. falciparum infected children (324.03 + 59.87) mg/dl as compared to the control (224.74 + 34.88) mg/dl. Parasite density showed a weak positive correlation between fibrinogen (p < 0.01, r = 0.461) and CRP (p < 0.01, r = 0.232). CRP was significantly increased (p < 0.05) in P. falciparum malaria infected children (21.52 + 35.59) mg/l as compared to the control (2.43 + 0.97) mg/l. In conclusion, P. falciparum malaria infection demonstrated a significant impact on fibrinogen and CRP.

scholarly journals Divergent pattern of genomic variation in Plasmodium falciparum and P. vivax

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2763 ◽  
Author(s):  
Preeti Goel ◽  
Gajinder Pal Singh
Keyword(s):  
Plasmodium Falciparum ◽  
Amino Acid ◽  
Large Scale ◽  
Genomic Variation ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Single Nucleotide ◽  
Evolutionary Response ◽  
Substitution Bias ◽  
Synonymous Sites

The two main species causing malaria in humans, Plasmodium falciparum and P. vivax, differ significantly from each other in their evolutionary response to common drugs, but the reasons for this are not clear. Here we utilized the recently available large-scale genome sequencing data from these parasites and compared the pattern of single nucleotide polymorphisms, which may be related to these differences. We found that there was a five-fold higher preference for AT nucleotides compared to GC nucleotides at synonymous single nucleotide polymorphism sites in P. vivax. The preference for AT nucleotides was also present at non-synonymous sites, which lead to amino acid changes favouring those with codons of higher AT content. The substitution bias was also present at low and moderately conserved amino acid positions, but not at highly conserved positions. No marked bias was found at synonymous and non-synonymous sites in P. falciparum. The difference in the substitution bias between P. falciparum and P. vivax found in the present study may possibly contribute to their divergent evolutionary response to similar drug pressures.

scholarly journals ConsHMM Atlas: conservation state annotations for major genomes and human genetic variation

2020 ◽  
Author(s):  
Adriana Arneson ◽  
Brooke Felsheim ◽  
Jennifer Chien ◽  
Jason Ernst
Keyword(s):  
Genetic Variation ◽  
Sequence Alignment ◽  
Human Genetic Variation ◽  
Web Interface ◽  
Single Nucleotide ◽  
Dna Sequence Alignment ◽  
Single Genome ◽  
Nucleotide Mutation ◽  
Allele Specific ◽  
Genome Annotations

AbstractConsHMM is a method recently introduced to annotate genomes into conservation states, which are defined based on the combinatorial and spatial patterns of which species align to and match a reference genome in a multi-species DNA sequence alignment. Previously, ConsHMM was only applied to a single genome for one multi-species sequence alignment. Here we apply ConsHMM to produce 22 additional genome annotations covering human and seven other organisms for a variety of multi-species alignments. Additionally, we have extended ConsHMM to generate allele specific annotations, which we used to produce conservation state annotations for every possible single nucleotide mutation in the human genome. Finally, we provide a web interface to interactively visualize parameters and annotation enrichments for ConsHMM models. These annotations and visualizations comprise the ConsHMM Atlas, which we expect will be a valuable resource for analyzing a variety of major genomes and genetic variation.

scholarly journals ConsHMM Atlas: conservation state annotations for major genomes and human genetic variation

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Adriana Arneson ◽  
Brooke Felsheim ◽  
Jennifer Chien ◽  
Jason Ernst
Keyword(s):  
Genetic Variation ◽  
Sequence Alignment ◽  
Human Genetic Variation ◽  
Web Interface ◽  
Single Nucleotide ◽  
Dna Sequence Alignment ◽  
Single Genome ◽  
Nucleotide Mutation ◽  
Allele Specific ◽  
Genome Annotations

Abstract ConsHMM is a method recently introduced to annotate genomes into conservation states, which are defined based on the combinatorial and spatial patterns of which species align to and match a reference genome in a multi-species DNA sequence alignment. Previously, ConsHMM was only applied to a single genome for one multi-species sequence alignment. Here, we apply ConsHMM to produce 22 additional genome annotations covering human and seven other organisms for a variety of multi-species alignments. Additionally, we extend ConsHMM to generate allele-specific annotations, which we use to produce conservation state annotations for every possible single-nucleotide mutation in the human genome. Finally, we provide a web interface to interactively visualize parameters and annotation enrichments for ConsHMM models. These annotations and visualizations comprise the ConsHMM Atlas, which we expect will be a valuable resource for analyzing a variety of major genomes and genetic variation.

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