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 ADRes: a computational pipeline for detecting molecular markers of Anti-malarial Drug Resistance, from Sanger sequencing data

2016 ◽  
Author(s):  
Setor Amuzu ◽  
Anita Ghansah
Keyword(s):  
Drug Resistance ◽  
Molecular Markers ◽  
Amino Acid ◽  
Sanger Sequencing ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Single Nucleotide ◽  
Artemisinin Derivatives ◽  
Base Calling ◽  
Sulphadoxine Pyrimethamine

AbstractBackgroundMalaria control efforts are stifled by the emergence and dispersal of parasite strains resistant to available anti-malarials. Amino acid changes in specific positions of proteins encoded by Plasmodium falciparum genes pfcrt, dhps, dhfr, and pfmdr1 are used as molecular markers of resistance to antimalarials such as chloroquine, sulphadoxine-pyrimethamine, as well as artemisinin derivatives. However, a challenge to the detection of single nucleotide polymorphisms (SNPs) in codons responsible for these amino acid changes, in several samples, is the scarcity of automated computational pipelines for molecular biologists to; rapidly analyze ABI (Applied Biosystems) Sanger sequencing data spanning the codons of interest in order to characterize these codons and detect these molecular markers of drug resistance. The pipeline described here is an attempt to address this need.MethodThis pipeline is a combination of existing tools, notably SAMtools and Burrows Wheeler Aligner (BWA), as well as custom Python and BASH scripts. It is designed to run on the UNIX shell, a command line interpreter. To characterize the codons associated with anti-malarial drug resistance (ADR) in a particular gene using this pipeline, the following options are required; a path to reference coding sequence of the gene in FASTA format, gene symbol (pfcrt, pfmdr1, dhps or dhfr), and a path to the directory of ABI sequencing trace files for the samples. With these inputs, the pipeline performs base calling and trimming, sequence alignment, and alignment parsing.ResultsThe output of the pipeline is a CSV (Comma-separated values) file of sample names, codons and their corresponding encoded amino acids. The data generated can be readily analyzed using widely available statistical or spreadsheet software, to determine the frequency of molecular markers of resistance to anti-malarials such as chloroquine, sulphadoxine-pyrimethamine and artemisinin derivatives.ConclusionsADRes is a quick and effective pipeline for detecting common molecular markers of anti-malarial drug resistance, and could be a useful tool for surveillance. The code, description, and instructions for using this pipeline are publicly available at http://setfelix.github.io/ADRes.

scholarly journals Intrinsic base substitution patterns in diverse species reveal links to cancer and metabolism

2019 ◽  
Author(s):  
Suzana P. Gelova ◽  
Kassidy N. Doherty ◽  
Salma Alasmar ◽  
Kin Chan
Keyword(s):  
Dna Damage ◽  
Large Scale ◽  
Genetic Selection ◽  
Sugar Metabolism ◽  
Base Substitution ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Single Nucleotide ◽  
Base Substitutions ◽  
Normal Human

AbstractAnalyses of large-scale sequencing data reveal that mutagenic processes create distinctive patterns of base substitutions, called mutational signatures. Here, we analyzed substitution patterns from seven model species and single nucleotide polymorphisms (SNPs) in 42 species, totalling >1.9 billion variants. We found that the base substitution patterns for many species most closely match mutational signature 5 in cancers. Signature 5 is also ubiquitous in cancers and normal human cells, suggesting similar patterns of mutation across species are likely due to conserved biochemistry. Finally, we present evidence from yeast that sugar metabolism is directly linked to this form of DNA damage. We propose that conserved metabolic processes in cells are coupled to continuous generation of mutations, which are acted upon by genetic selection to drive the evolution of species, and cancers.One Sentence SummaryEnergy metabolism produces DNA damage leading to similar patterns of base substitutions in many species and in human cancers.

Automated Identification of Single Nucleotide Polymorphisms from Sequencing Data

2003 ◽  
Vol 01 (02) ◽  
pp. 253-265 ◽  
Author(s):  
Masazumi Takahashi ◽  
Fumihiko Matsuda ◽  
Nino Margetic ◽  
Mark Lathrop
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Polymerase Chain Reaction Amplification ◽  
Peak Height ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Automated Identification ◽  
Single Nucleotide ◽  
Snp Data ◽  
The Difference

The single nucleotide polymorphism (SNP) is the difference of the DNA sequence between individuals and provides abundant information about genetic variation. Large scale discovery of high frequency SNPs is being undertaken using various methods. However, the publicly available SNP data sometimes need to be verified. If only a particular gene locus is concerned, locus-specific polymerase chain reaction amplification may be useful. Problem of this method is that the secondary peak has to be measured. We have analyzed trace data from conventional sequencing equipment and found an applicable rule to discern SNPs from noise. The rule is applied to multiply aligned sequences with a trace and the peak height of the traces are compared between samples. We have developed software that integrates this function to automatically identify SNPs. The software works accurately for high quality sequences and also can detect SNPs in low quality sequences. Further, it can determine allele frequency, display this information as a bar graph and assign corresponding nucleotide combinations. It is also designed for a person to verify and edit sequences easily on the screen. It is very useful for identifying de novo SNPs in a DNA fragment of interest.

scholarly journals Implications of the Novel Mutations in the SARS-CoV-2 Genome for Transmission, Disease Severity, and the Vaccine Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Hikmet Akkiz
Keyword(s):  
Amino Acid ◽  
Disease Severity ◽  
Vaccine Development ◽  
Experimental Studies ◽  
Spike Protein ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Novel Mutations ◽  
Single Nucleotide ◽  
The Impact

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease 2019 (COVID-19), has been identified in China in late December 2019. SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA betacoronavirus of the Coronaviridae family. Coronaviruses have genetic proofreading mechanism that corrects copying mistakes and thus SARS-CoV-2 genetic diversity is extremely low. Despite lower mutation rate of the virus, researchers have detected a total of 12,706 mutations in the SARS-CoV-2 genome, the majority of which were single nucleotide polymorphisms. Sequencing data revealed that the SARS-CoV-2 accumulates two-single nucleotide mutations per month in its genome. Recently, an amino acid aspartate (D) to glycine (G) (D614G) mutation due to an adenine to guanine nucleotide change at position 23,403 at the 614th amino-acid position of the spike protein in the original reference genotype has been identified. The SARS-CoV-2 viruses that carry the spike protein D614G mutation have become dominant variant around the world. The D614G mutation has been found to be associated with 3 other mutations in the spike protein. Clinical and pseudovirus experimental studies have demonstrated that the spike protein D614G mutation alters the virus phenotype. However, the impact of the mutation on the rate of transmission between people, disease severity and the vaccine and therapeutic development remains unclear. Three variants of SARS-CoV-2 have recently been identified. They are B.1.1.7 (UK) variant, B.1.351 (N501Y.V2, South African) variant and B.1.1.28 (Brazilian) variant. Epidemiological data suggest that they have a higher transmissibility than the original variant. There are reports that some vaccines are less efficacious against the B.1.351 variant. This review article discusses the effects of novel mutations in the SARS-CoV-2 genome on transmission, clinical outcomes and vaccine development.

Protein Variation in ADH and ADH-RELATED in Drosophila pseudoobscura: Linkage Disequilibrium Between Single Nucleotide Polymorphisms and Protein Alleles

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 673-687
Author(s):  
Stephen W Schaeffer ◽  
C Scott Walthour ◽  
Donna M Toleno ◽  
Anna T Olek ◽  
Ellen L Miller
Keyword(s):  
Linkage Disequilibrium ◽  
Single Nucleotide Polymorphisms ◽  
Drosophila Pseudoobscura ◽  
Linkage Disequilibrium Mapping ◽  
Nucleotide Polymorphisms ◽  
Neutral Model ◽  
Significant Linkage Disequilibrium ◽  
Single Nucleotide ◽  
Synonymous Sites ◽  
Significant Linkage

Abstract A 3.5-kb segment of the alcohol dehydrogenase (Adh) region that includes the Adh and Adh-related genes was sequenced in 139 Drosophila pseudoobscura strains collected from 13 populations. The Adh gene encodes four protein alleles and rejects a neutral model of protein evolution with the McDonald-Kreitman test, although the number of segregating synonymous sites is too high to conclude that adaptive selection has operated. The Adh-related gene encodes 18 protein haplotypes and fails to reject an equilibrium neutral model. The populations fail to show significant geographic differentiation of the Adh-related haplotypes. Eight of 404 single nucleotide polymorphisms (SNPs) in the Adh region were in significant linkage disequilibrium with three ADHR protein alleles. Coalescent simulations with and without recombination were used to derive the expected levels of significant linkage disequilibrium between SNPs and 18 protein haplotypes. Maximum levels of linkage disequilibrium are expected for protein alleles at moderate frequencies. In coalescent models without recombination, linkage disequilibrium decays between SNPs and high frequency haplotypes because common alleles mutate to haplotypes that are rare or that reach moderate frequency. The implication of this study is that linkage disequilibrium mapping has the highest probability of success with disease-causing alleles at frequencies of 10%.

scholarly journals A NOTE ON PHASING LONG GENOMIC REGIONS USING LOCAL HAPLOTYPE PREDICTIONS

2006 ◽  
Vol 04 (03) ◽  
pp. 639-647 ◽  
Author(s):  
ELEAZAR ESKIN ◽  
RODED SHARAN ◽  
ERAN HALPERIN
Keyword(s):  
Large Scale ◽  
Computational Cost ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Novel Approach ◽  
Maximum Likelihood Criterion ◽  
The Common ◽  
Genomic Regions ◽  
High Computational Cost ◽  
Combining Information

The common approaches for haplotype inference from genotype data are targeted toward phasing short genomic regions. Longer regions are often tackled in a heuristic manner, due to the high computational cost. Here, we describe a novel approach for phasing genotypes over long regions, which is based on combining information from local predictions on short, overlapping regions. The phasing is done in a way, which maximizes a natural maximum likelihood criterion. Among other things, this criterion takes into account the physical length between neighboring single nucleotide polymorphisms. The approach is very efficient and is applied to several large scale datasets and is shown to be successful in two recent benchmarking studies (Zaitlen et al., in press; Marchini et al., in preparation). Our method is publicly available via a webserver at .

Associations between varied susceptibilities of PfATP4 inhibitors and genotypes in Ugandan Plasmodium falciparum isolates

2021 ◽  
Author(s):  
Oriana Kreutzfeld ◽  
Stephanie A. Rasmussen ◽  
Aarti A. Ramanathan ◽  
Patrick K. Tumwebaze ◽  
Oswald Byaruhanga ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Single Nucleotide Polymorphisms ◽  
Ex Vivo ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Field Isolates ◽  
Frequent Mutations ◽  
Mixed Field ◽  
P Type

Among novel compounds under recent investigation as potential new antimalarial drugs are three independently developed inhibitors of the Plasmodium falciparum P-type ATPase (PfATP4): KAE609 (cipargamin), PA92, and SJ733. We assessed ex vivo susceptibilities to these compounds of 374 fresh P. falciparum isolates collected in Tororo and Busia districts, Uganda from 2016-2019. Median IC 50 s were 65 nM for SJ733, 9.1 nM for PA92, and 0.5 nM for KAE609. Sequencing of pfatp4 for 218 of these isolates demonstrated many non-synonymous single nucleotide polymorphisms; the most frequent mutations were G1128R (69% of isolates mixed or mutant), Q1081K/R (68%), G223S (25%), N1045K (16%) and D1116G/N/Y (16%). The G223S mutation was associated with decreased susceptibility to SJ733, PA92 and KAE609. The D1116G/N/Y mutations were associated with decreased susceptibility to SJ733, and the presence of mutations at both codons 223 and 1116 was associated with decreased susceptibility to PA92 and SJ733. In all of these cases, absolute differences in susceptibilities of wild type (WT) and mutant parasites were modest. Analysis of clones separated from mixed field isolates consistently identified mutant clones as less susceptible than WT. Analysis of isolates from other sites demonstrated presence of the G223S and D1116G/N/Y mutations across Uganda. Our results indicate that malaria parasites circulating in Uganda have a number of polymorphisms in PfATP4 and that modestly decreased susceptibility to PfATP4 inhibitors is associated with some mutations now present in Ugandan parasites.

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.

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