scholarly journals Single Nucleotide Polymorphism Analysis of Pvmdr-1 in Plasmodium Vivax Isolated from Military Personnel of Republic of Korea in 2016 and 2017

2021 ◽  
Author(s):  
Jin-Jong Bong ◽  
Wonsig Lee ◽  
Qu-Ehn Park ◽  
Kyung Tae Noh
Keyword(s):  
Plasmodium Vivax ◽  
Chloroquine Resistance ◽  
Republic Of Korea ◽  
Multi Drug Resistance ◽  
Clinical Samples ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Malaria Chemoprophylaxis ◽  
Synonymous Mutations

Abstract Background: Malaria chemoprophylaxis using chloroquine (CQ) and primaquine (PQ) has been administered to resident soldiers in the 3rd Army of Republic of Korea (ROK) to prevent malaria infection since the year 1997. Due to mass chemoprophylaxis against malaria, concern exists about occurrence of chloroquine resistance (CQR). Herein, we investigated the single nucleotide polymorphisms (SNPs) of the Plasmodium vivax multi-drug resistance protein-1 (pvmdr-1) gene to monitor the risk of CQR. Methods: SNPs of the pvmdr-1 gene were analyzed in 73 soldiers of the 3rd Army of ROK diagnosed with infection by Plasmodium vivax (P. vivax). Results: Quintuple mutations (G698S, L845F, M908L, T958M, and F1076L) were detected in 73 soldiers. Mutation in the Y541C position was firstly detected in soldiers at a frequency of 1.3% (1/73). In addition, synonymous mutations were detected at positions K44, L493, T529, and E1233. Based on these SNPs, pvmdr-1 sequences of ROK were classified into 6 haplotypes. The phylogenetic analysis closed to Type of North Korean showed that P. vivax malaria of ROK could be a reason of influx from North Korea. In this study, there was no therapeutic resistance (CQ-mediated parasite clearance within 72 hours) for clinical samples that possessed various SNPs of pvmdr-1. Various SNPs including a newly identified non-synonymous mutation (Y541C) had been introduced into P. vivax malaria-endemic areas in ROK. Conclusions: Our study showed that synonymous and non-synonymous mutations of pvmdr-1 were introduced to the malaria chemoprophylaxis-executed regions of ROK from 2016 to 2017. Thus, to prevent the emergence of CQR, continuous surveillance for SNPs of pvmdr-1 related with CQR in the malaria-endemic regions of ROK is essential.

Single Nucleotide Polymorphism Analysis of Pvmdr-1 in Plasmodium Vivax Isolated From Military Personnel of Republic of Korea in 2016 and 2017

2021 ◽  
Author(s):  
Jin-Jong Bong ◽  
Wonsig Lee ◽  
Qu-Ehn Park ◽  
Kyung Tae Noh
Keyword(s):  
Plasmodium Vivax ◽  
Chloroquine Resistance ◽  
Republic Of Korea ◽  
Multi Drug Resistance ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Malaria Chemoprophylaxis ◽  
Resistance Protein

Abstract Background: Malaria chemoprophylaxis using chloroquine and primaquine has been administered to resident soldiers in the 3rd Army of Republic of Korea (ROK) to prevent malaria infection since the year 1997. Due to mass chemoprophylaxis against malaria, concern exists about occurrence of chloroquine resistance. Herein, we investigated the single nucleotide polymorphisms (SNPs) of the Plasmodium vivax multi-drug resistance protein-1 (Pvmdr-1) gene to monitor the risk of chloroquine resistance.Methods: To evaluate the risk of malaria chemoprophylaxis, SNPs of the Pvmdr-1 gene were analysed in 73 soldiers of the 3rd Army of ROK diagnosed with infection by Plasmodium vivax. Results: Quintuple mutations (G698S, L845F, M908L, T958M, and F1076L) were detected in 73 soldiers. Mutation in the Y541C position was detected in soldiers at a frequency of 1.3% (1/73). In addition, silent mutations were detected at positions 44K, 493L, 529T, and 1233E. Based on these SNPs, Pvmdr-1 sequences of ROK were classified into 6 haplotypes. Phylogenetic analysis showed that the neighbourhood of the 6 haplotypes were Chaina_NB-16 and Papua New Guinea-PNG58 (Figure 1).Conclusions: Genetic- or phenotypic-based chloroquine resistance was not observed. However, various SNPs including a newly identified non-synonymous mutation (Y541C) have been introduced into Plasmodium vivax malaria endemic areas in ROK. Thus, to prevent the emergence of chloroquine resistance, continuous surveillance for SNPs of Pvmdr-1 related with chloroquine resistance is essential in the malaria chemoprophylaxis-executed regions of ROK.

scholarly journals Analysis of Single-Nucleotide Polymorphisms in the crt-o and mdr1 Genes of Plasmodium vivax among Chloroquine-Resistant Isolates from the Brazilian Amazon Region

2009 ◽  
Vol 53 (8) ◽  
pp. 3561-3564 ◽  
Author(s):  
Pamela Orjuela-Sánchez ◽  
Franklin Simões de Santana Filho ◽  
Ariane Machado-Lima ◽  
Yonne Francis Chehuan ◽  
Mônica Regina Farias Costa ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Plasmodium Vivax ◽  
Brazilian Amazon ◽  
Chloroquine Resistance ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Noncoding Sequences ◽  
Brazilian Amazon Region ◽  
Virulent Phenotype

ABSTRACT Plasmodium vivax parasites with chloroquine resistance (CQR) are already circulating in the Brazilian Amazon. Complete single-nucleotide polymorphism (SNP) analyses of coding and noncoding sequences of the pvmdr1 and pvcrt-o genes revealed no associations with CQR, even if some mutations had not been randomly selected. In addition, striking differences in the topologies and numbers of SNPs in these transporter genes between P. vivax and P. falciparum reinforce the idea that mechanisms other than mutations may explain this virulent phenotype in P. vivax.

Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2709-2712 ◽  
Author(s):  
Maria E. Sarasquete ◽  
Ramon García-Sanz ◽  
Luis Marín ◽  
Miguel Alcoceba ◽  
Maria C. Chillón ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cytochrome P450 ◽  
Genome Wide Association Study ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome

Abstract We have explored the potential role of genetics in the development of osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients under bisphosphonate therapy. A genome-wide association study was performed using 500 568 single nucleotide polymorphisms (SNPs) in 2 series of homogeneously treated MM patients, one with ONJ (22 MM cases) and another without ONJ (65 matched MM controls). Four SNPs (rs1934951, rs1934980, rs1341162, and rs17110453) mapped within the cytochrome P450-2C gene (CYP2C8) showed a different distribution between cases and controls with statistically significant differences (P = 1.07 × 10−6, P = 4.231 × 10−6, P = 6.22 × 10−6, and P = 2.15 × 10−6, respectively). SNP rs1934951 was significantly associated with a higher risk of ONJ development even after Bonferroni correction (P corrected value = .02). Genotyping results displayed an overrepresentation of the T allele in cases compared with controls (48% vs 12%). Thus, individuals homozygous for the T allele had an increased likelihood of developing ONJ (odds ratio 12.75, 95% confidence interval 3.7-43.5).

scholarly journals From raw reads to trees: Whole genome SNP phylogenetics across the tree of life

2015 ◽  
Author(s):  
Sanaa Afroz Ahmed ◽  
Chien-Chi Lo ◽  
Po-E Li ◽  
Karen W Davenport ◽  
Patrick S.G. Chain
Keyword(s):  
Ad Hoc ◽  
Phylogenetic Reconstruction ◽  
Clinical Samples ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Complex Samples ◽  
Phylogenetic Characterization ◽  
Genome Wide ◽  
Genome Assemblies

Next-generation sequencing is increasingly being used to examine closely related organisms. However, while genome-wide single nucleotide polymorphisms (SNPs) provide an excellent resource for phylogenetic reconstruction, to date evolutionary analyses have been performed using different ad hoc methods that are not often widely applicable across different projects. To facilitate the construction of robust phylogenies, we have developed a method for genome-wide identification/characterization of SNPs from sequencing reads and genome assemblies. Our phylogenetic and molecular evolutionary (PhaME) analysis software is unique in its ability to take reads and draft/complete genome(s) as input, derive core genome alignments, identify SNPs, construct phylogenies and perform evolutionary analyses. Several examples using genomes and read datasets for bacterial, eukaryotic and viral linages demonstrate the broad and robust functionality of PhaME. Furthermore, the ability to incorporate raw metagenomic reads from clinical samples with suspected infectious agents shows promise for the rapid phylogenetic characterization of pathogens within complex samples.

Timing during translation matters: synonymous mutations in human pathologies influence protein folding and function

2018 ◽  
Vol 46 (4) ◽  
pp. 937-944 ◽  
Author(s):  
Robert Rauscher ◽  
Zoya Ignatova
Keyword(s):  
Protein Folding ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Synonymous Mutations ◽  
Translation Velocity ◽  
Disease Penetrance ◽  
And Function ◽  
Related Proteins ◽  
Translational Speed ◽  
Fine Tune

Ribosomes translate mRNAs with non-uniform speed. Translation velocity patterns are a conserved feature of mRNA and have evolved to fine-tune protein folding, expression and function. Synonymous single-nucleotide polymorphisms (sSNPs) that alter programmed translational speed affect expression and function of the encoded protein. Synergistic advances in next-generation sequencing have led to the identification of sSNPs associated with disease penetrance. Here, we draw on studies with disease-related proteins to enhance our understanding of mechanistic contributions of sSNPs to functional alterations of the encoded protein. We emphasize the importance of identification of sSNPs along with disease-causing mutations to understand genotype–phenotype relationships.

scholarly journals A multiparametric approach to improve the prediction of response to immunotherapy in patients with metastatic NSCLC

2020 ◽  
Author(s):  
Marzia Del Re ◽  
Federico Cucchiara ◽  
Eleonora Rofi ◽  
Lorenzo Fontanelli ◽  
Iacopo Petrini ◽  
...  
Keyword(s):  
Mutational Load ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Synonymous Mutations ◽  
Metastatic Nsclc ◽  
Molecular Determinants ◽  
Droplet Pcr ◽  
Ifn Γ ◽  
Nsclc Patients ◽  
Next Generation Sequencing Ngs

Abstract Background It is still unclear how to combine biomarkers to identify patients who will truly benefit from anti-PD-1 agents in NSCLC. This study investigates exosomal mRNA expression of PD-L1 and IFN-γ, PD-L1 polymorphisms, tumor mutational load (TML) in circulating cell-free DNA (cfDNA) and radiomic features as possible predictive markers of response to nivolumab and pembrolizumab in metastatic NSCLC patients. Methods Patients were enrolled and blood (12 ml) was collected at baseline before receiving anti-PD-1 therapy. Exosome-derived mRNA and cfDNA were extracted to analyse PD-L1 and IFN-γ expression and tumor mutational load (TML) by digital droplet PCR (ddPCR) and next-generation sequencing (NGS), respectively. The PD-L1 single nucleotide polymorphisms (SNPs) c.-14-368 T > C and c.*395G > C, were analysed on genomic DNA by Real-Time PCR. A radiomic analysis was performed on the QUIBIM Precision® V3.0 platform. Results Thirty-eight patients were enrolled. High baseline IFN-γ was independently associated with shorter median PFS (5.6 months vs. not reached p = 0.0057), and levels of PD-L1 showed an increase at 3 months vs. baseline in patients who progressed (p = 0.01). PD-L1 baseline levels showed significant direct and inverse relationships with radiomic features. Radiomic features also inversely correlated with PD-L1 expression in tumor tissue. In subjects receiving nivolumab, median PFS was shorter in carriers of c.*395GG vs. c.*395GC/CC genotype (2.3 months vs. not reached, p = 0.041). Lastly, responders had higher non-synonymous mutations and more links between co-occurring genetic somatic mutations and ARID1A alterations as well. Conclusions A combined multiparametric approach may provide a better understanding of the molecular determinants of response to immunotherapy.

scholarly journals MassARRAY-based single nucleotide polymorphism analysis in breast cancer of north Indian population

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Divya Bakshi ◽  
Ashna Nagpal ◽  
Varun Sharma ◽  
Indu Sharma ◽  
Ruchi Shah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Mutations ◽  
Cost Effective ◽  
P Value ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Cost Effective Method ◽  
Common Genetic Variants ◽  
Underlying Causes

Abstract Background Breast Cancer (BC) is associated with inherited gene mutations. High throughput genotyping of BC samples has led to the identification and characterization of biomarkers for the diagnosis of BC. The most common genetic variants studied are SNPs (Single Nucleotide Polymorphisms) that determine susceptibility to an array of diseases thus serving as a potential tool for identifying the underlying causes of breast carcinogenesis. Methods SNP genotyping employing the Agena MassARRAY offers a robust, sensitive, cost-effective method to assess multiple SNPs and samples simultaneously. In this present study, we analyzed 15 SNPs of 14 genes in 550 samples (150 cases and 400 controls). We identified four SNPs of genes TCF21, SLC19A1, DCC, and ERCC1 showing significant association with BC in the population under study. Results The SNPs were rs12190287 (TCF21) having OR 1.713 (1.08–2.716 at 95% CI) p-value 0.022 (dominant), rs1051266 (SLC19A1) having OR 3.461 (2.136–5.609 at 95% CI) p-value 0.000000466 (dominant), rs2229080 (DCC) having OR 0.6867 (0.5123–0.9205 at 95% CI) p-value 0.0116 (allelic) and rs2298881 (ERCC1) having OR 0.669 (0.46–0.973 at 95% CI), p-value 0.035 (additive) respectively. The in-silico analysis was further used to fortify the above findings. Conclusion It is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability.

scholarly journals Single Nucleotide Polymorphisms in Genes Associated with Isoniazid Resistance in Mycobacterium tuberculosis

2003 ◽  
Vol 47 (4) ◽  
pp. 1241-1250 ◽  
Author(s):  
Srinivas V. Ramaswamy ◽  
Robert Reich ◽  
Shu-Jun Dou ◽  
Linda Jasperse ◽  
Xi Pan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Single Nucleotide Polymorphisms ◽  
Molecular Genetic ◽  
Mycolic Acid ◽  
Genetic Group ◽  
Clinical Isolates ◽  
Central Component ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

ABSTRACT Isoniazid (INH) is a central component of drug regimens used worldwide to treat tuberculosis. Previous studies have identified resistance-associated mutations in katG, inhA, kasA, ndh, and the oxyR-ahpC intergenic region. DNA microarray-based experiments have shown that INH induces several genes in Mycobacterium tuberculosis that encode proteins physiologically relevant to the drug's mode of action. To gain further insight into the molecular genetic basis of INH resistance, 20 genes implicated in INH resistance were sequenced for INH resistance-associated mutations. Thirty-eight INH-monoresistant clinical isolates and 86 INH-susceptible isolates of M. tuberculosis were obtained from the Texas Department of Health and the Houston Tuberculosis Initiative. Epidemiologic independence was established for all isolates by IS6110 restriction fragment length polymorphism analysis. Susceptible isolates were matched with resistant isolates by molecular genetic group and IS6110 profiles. Spoligotyping was done with isolates with five or fewer IS6110 copies. A major genetic group was established on the basis of the polymorphisms in katG codon 463 and gyrA codon 95. MICs were determined by the E-test. Semiquantitative catalase assays were performed with isolates with mutations in the katG gene. When the 20 genes were sequenced, it was found that 17 (44.7%) INH-resistant isolates had a single-locus, resistance-associated mutation in the katG, mabA, or Rv1772 gene. Seventeen (44.7%) INH-resistant isolates had resistance-associated mutations in two or more genes, and 76% of all INH-resistant isolates had a mutation in the katG gene. Mutations were also identified in the fadE24, Rv1592c, Rv1772, Rv0340, and iniBAC genes, recently shown by DNA-based microarray experiments to be upregulated in response to INH. In general, the MICs were higher for isolates with mutations in katG and the isolates had reduced catalase activities. The results show that a variety of single nucleotide polymorphisms in multiple genes are found exclusively in INH-resistant clinical isolates. These genes either are involved in mycolic acid biosynthesis or are overexpressed as a response to the buildup or cellular toxicity of INH.

Single Nucleotide Polymorphisms of FCRL3 in Iranian Patients with Behcet’s Disease

2020 ◽  
Author(s):  
Farhad SHAHRAM ◽  
Javad KAZEMI ◽  
Mahmoud MAHMOUDI ◽  
Zohreh JADALI
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Behcet's Disease ◽  
Significant Difference ◽  
Iranian Patients

Background: Both genetic and environmental factors influence, susceptibility to autoimmune disorders including Behcet’s disease (BD). FCRL3 (Fc receptor like 3 genes), a novel immunoregulatory gene, has recently been reported as a new promising candidate gene for general autoimmunity. This study was conducted to explore the potential association of FCRL3 polymorphisms with BD. Methods: This study was conducted from 2010 to 2015 in Tehran University of Medical Sciences, Tehran, Iran. Four single-nucleotide polymorphisms of FCRL3 (rs7528684, rs11264799, rs945635, and rs3761959) were genotyped in 220 patients and 220 healthy controls. Typing of the polymorphisms in this case-control study was carried out using polymerase chain reaction-restriction fragment length polymorphism analysis. Results: Analysis of the alleles revealed a significantly lower frequency of the A allele at the -169 site (rs7528684) in BD patients compared with that in controls (P=0.000, 66.4% versus 82%, χ2= 30.23). Moreover, a significant lower frequency of AA genotype and higher frequency of GG genotype was recorded for rs7528684. There was also relationship between posterior uveitis as a clinical sign of disease and polymorphism of allele A at the -169 site (P=0.015). Conclusion: This study revealed a significant difference in both allele and genotype frequency at position -169 of FCRL3 gene between Iranian patients with BD and normal subjects. These data suggest FCRL3 gene polymorphisms might be the autoimmunity risk factor for BD.

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