Genetic diversity analysis of the D614G mutation in SARS-CoV-2

2020 ◽  
Author(s):  
Pierre Teodósio Felix ◽  
Dallynne Bárbara Ramos Venâncio ◽  
Eduarda Doralice Alves Braz Da Silva ◽  
Robson da Silva Ramos
Keyword(s):  
Genetic Diversity ◽  
Molecular Diversity ◽  
Divergence Time ◽  
Population Variation ◽  
Fixation Index ◽  
Evolutionary Divergence ◽  
Mutant Form ◽  
Peace Of Mind ◽  
Risk Of Death ◽  
Increased Risk

AbstractIn this work, we evaluated the levels of genetic diversity in 18 genomes of SARS-CoV-2 carrying the D614G mutation, coming from Malaysia and Venezuela and publicly available at the National Center of Biotechnology and Information (NCBI). These haplotypes were previously used for phylogenetic analysis, following the LaBECom protocols. All gaps and unconserved sites were extracted for the construction of a phylogenetic tree. As specific methodologies for paired FST estimators, Molecular Variance (AMOVA), Genetic Distance, mismatch, demographic and spatial expansion analyses, molecular diversity and evolutionary divergence time analyses, 20,000 random permutations were always used. The results revealed the presence of only 57 sites of polymorphic and parsimonium-informative among the 29,827bp analyzed and the analyses based on FST values confirmed the presence of two distinct genetic entities with fixation index of 22% and with a higher component of population variation (78.14%). Tau variations revealed a significant time of divergence, supported by mismatch analysis of the observed distribution (τ = 42%). It is safe to say that the small number of existing polymorphisms should not reflect major changes in the protein products of viral populations in both countries and this consideration provides the safety that, although there are differences in the haplotypes studied, these differences are minimal for both regions analyzed geographically and, therefore, it seems safe to extrapolate the levels of polymorphism and molecular diversity found in the samples for other mutant genomes of SARS-CoV-2 in other countries. This reduces speculation about the possibility of large differences between mutant strains of SARS-CoV-2 (D614G) and wild strains, at least at the level of their protein products, although the mutant form has higher transmission speed and infection. The analyses suggest that possible variations in protein products, of the wild virus in relation to its mutant form, should be minimal, bringing peace of mind as to the increased risk of death from the new form of the virus, as well as possible problems of gradual adjustments in some molecular targets for vaccines.

scholarly journals Biomathematical models for genetic diversity analyses in complete genomes of SARS-CoV-2

2020 ◽  
Author(s):  
Robson da Silva Ramos ◽  
Pierre Teodósio Felix ◽  
Dallynne Bárbara Ramos Venâncio ◽  
Cícero Batista do Nascimento Filho ◽  
Antônio João Paulino
Keyword(s):  
Genetic Diversity ◽  
Phylogenetic Trees ◽  
Molecular Diversity ◽  
Phylogenetic Analyses ◽  
Divergence Time ◽  
Random Permutation ◽  
Evolutionary Divergence ◽  
Spatial Expansion ◽  
Molecular Variance ◽  
Complete Genomes

AbstractIn this work, we evaluated the levels of genetic diversity in 38 complete genomes of SARS-CoV-2, publicly available on the National Center for Biotechnology Information (NCBI) platform and from six countries in South America (Brazil, Chile, Peru, Colombia, Uruguay and Venezuela with 16, 11, 1, 1, 1, 7 haplotypes, respectively), all with an extension of 29,906 bp and Phred values ≥ 40. These haplotypes were previously used for phylogenetic analyses, following the alignment protocols of the MEGA X software; where all gaps and unconserved sites were extracted for the construction of phylogenetic trees. The specific methodologies for Paired FST estimators, Molecular Variance (AMOVA), Genetic Distance, mismatch, demographic and spatial expansion analyses, molecular diversity and evolutionary divergence time analyses, were obtained using 20,000 random permutation.

scholarly journals Molecular variance analysis (AMOVA) and levels of genetic diversity of complete genome of SARS-CoV-2 virus from of six South American Countries

2020 ◽  
Author(s):  
Pierre Teodosio Felix ◽  
Robson da Silva Ramos ◽  
Sara da Silva Nascimento ◽  
Willams Felipe Ferreira Silva ◽  
Maria Dara Pereira da Silva ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
South America ◽  
Molecular Diversity ◽  
Evolutionary Divergence ◽  
South American ◽  
Significant Similarity ◽  
Sanitation And Hygiene ◽  
Hygiene Measures ◽  
Basic Sanitation ◽  
Evolutionary Aspects

Abstract Although some Countries in South America have implemented laboratory and patient management protocols for the new coronavirus, the lack of access to basic sanitation and hygiene measures, as well as the lack of drugs and vaccines, has significantly interfered with the epidemiological mechanics of the virus, emphasizing its implications. Therefore, trying to understand the evolutionary aspects of the virus, emerges as another strategy that can help in the most varied measures of prophylaxis. In this work, we evaluated the levels of genetic diversity in 38 complete Genomes of SARS-CoV-2 from six countries in South America, using specific methodologies for paired FST, AMOVA, mismatch, demographic and spatial expansions, molecular diversity and for the time of evolutionary divergence. The analyses showed non-significant evolutionary divergences within and between the six countries, as well as a significant similarity to the time of genetic evolutionary divergence between all populations. Thus, it seems safe to affirm that we will find similar results for the other Countries of South America, reducing speculation about the existence of rapid and silent mutations that, although there are as we have shown in this work, do not increase, until this moment, the genetic variability of the Virus, a fact that would hinder the work with molecular targets for vaccines and drugs in general.

scholarly journals Genetic diversity and population structure of indigenous chicken of Bangladesh using microsatellite markers

2020 ◽  
Vol 33 (11) ◽  
pp. 1732-1740
Author(s):  
Muhammad Abdur Rashid ◽  
Prabuddha Manjula ◽  
Shakila Faruque ◽  
A. K. Fazlul Haque Bhuiyan ◽  
Dongwon Seo ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Population Structure ◽  
Genetic Distance ◽  
Microsatellite Markers ◽  
Polymorphic Information Content ◽  
Population Variation ◽  
Fixation Index ◽  
Indigenous Chicken ◽  
Diversity Measures ◽  
Red Jungle Fowl

Objective: The objectives of this study were to investigate the genetic diversity, population structure and relatedness among the five chicken populations of Bangladesh using microsatellite markers.Methods: A total of 161 individuals representing 5 chicken populations (non-descript Deshi [ND], naked neck [NN], hilly [HI], Aseel [AS], and red jungle fowl [JF]) were included in this study to investigate genetic diversity measures, population structure, genetic distance and phylogenetic relationships. Genotyping was performed using 16 selected polymorphic microsatellite markers distributed across 10 chromosomes.Results: The average observed and expected heterozygosity, mean number of alleles and polymorphic information content were found to be 0.67±0.01, 0.70±0.01, 10.7 and 0.748, respectively in the studied populations. The estimated overall fixation index across the loci (F), heterozygote deficiency within (F<sub>IS</sub>) and among (F<sub>IT</sub>) chicken populations were 0.04±0.02, 0.05 and 0.16, respectively. Analysis of molecular variance analysis revealed 88.07% of the total genetic diversity was accounted for within population variation and the rest 11.93% was incurred with population differentiation (F<sub>ST</sub>). The highest pairwise genetic distance (0.154) was found between ND and AS while the lowest distance was between JF and AS (0.084). Structure analysis depicted that the studied samples can be categorized into four distinct types or varieties (ΔK = 3.74) such as ND, NN, and HI where AS and JF clustered together as an admixed population. The Neighbor-Joining phylogenetic tree and discriminant analysis of principal component also showed close relatedness among three chicken varieties namely AS, HI, and JF.Conclusion: The results reflected that indigenous chicken of Bangladesh still possess rich genetic diversity but weak differentiation among the studied populations. This finding provides some important insight on genetic diversity measures that could support the designing and implementing of future breeding plans for indigenous chickens of Bangladesh.

scholarly journals The demographic and adaptive history of the African green monkey

2017 ◽  
Author(s):  
Susanne P. Pfeifer
Keyword(s):  
Genetic Diversity ◽  
Demographic History ◽  
Divergence Time ◽  
African Green Monkey ◽  
Population Variation ◽  
Population Divergence ◽  
Nucleotide Polymorphisms ◽  
Divergence Time Estimates ◽  
Green Monkey ◽  
History Of

AbstractRelatively little is known about the evolutionary history of the African green monkey (genus Chlorocebus) due to the lack of sampled polymorphism data from wild populations. Yet, this characterization of genetic diversity is not only critical for a better understanding of their own history, but also for human biomedical research given that they are one of the most widely used primate models. Here, I analyze the demographic and selective history of the African green monkey, utilizing one of the most comprehensive catalogs of wild genetic diversity to date, consisting of 1,795,643 autosomal single nucleotide polymorphisms in 25 individuals, representing all five major populations: C. a. aethiops, C. a. cynosurus, C. a. pygerythrus, C. a. sabaeus, and C. a tantalus. Assuming a mutation rate of 5.9 × 10−9 per base pair per generation and a generation time of 8.5 years, divergence time estimates range from 523-621kya for the basal split of C. a. aethiops from the other four populations. Importantly, the resulting tree characterizing the relationship and split-times between these populations differs significantly from that presented in the original genome paper, owing to their neglect of within-population variation when calculating between population-divergence. In addition, I find that the demographic history of all five populations is well explained by a model of population fragmentation and isolation, rather than novel colonization events. Finally, utilizing these demographic models as a null, I investigate the selective history of the populations, identifying candidate regions potentially related to adaptation in response to pathogen exposure.

scholarly journals Levels of genetic diversity of SARS-CoV-2 virus: reducing speculations about the genetic variability of the virus in South America

2020 ◽  
Author(s):  
Pierre Teodósio Felix ◽  
Cícero Batista do Nascimento Filho ◽  
Robson da Silva Ramos ◽  
Antônio João Paulino ◽  
Dallynne Bárbara Ramos Venâncio
Keyword(s):  
Genetic Diversity ◽  
Genetic Variability ◽  
South America ◽  
Molecular Diversity ◽  
Molecular Targets ◽  
The Other ◽  
Evolutionary Divergence ◽  
Significant Similarity ◽  
Complete Genomes

AbstractIn this work, we evaluated the levels of genetic diversity in 38 complete Genomes of SARS-CoV-2 from six countries in South America, using specific methodologies for paired FST, AMOVA, mismatch, demographic and spatial expansions, molecular diversity and for the time of evolutionary divergence. The analyses showed non-significant evolutionary divergences within and between the six countries, as well as a significant similarity to the time of genetic evolutionary divergence between all populations. Thus, it seems safe to affirm that we will find similar results for the other Countries of South America, reducing speculation about the existence of rapid and silent mutations that, although there are as we have shown in this work, do not increase, until this moment, the genetic variability of the Virus, a fact that would hinder the work with molecular targets for vaccines and drugs in general.

EFFECTS OF SMOKING ON THE DISEASE PROGNOSIS IN CANCER PATIENTS

2019 ◽  
Vol 65 (3) ◽  
pp. 321-329
Author(s):  
David Zaridze ◽  
Anush Mukeriya
Keyword(s):  
Smoking Cessation ◽  
Cancer Patients ◽  
Malignant Tumors ◽  
Scientific Data ◽  
Second Primary ◽  
Primary Tumors ◽  
Smoking Intensity ◽  
Risk Of Death ◽  
Disease Prognosis ◽  
Increased Risk

Smoking not only increases the risk of the development of malignant tumors (MT), but affects the disease prognosis, mortality and survivability of cancer patients. The link between the smoking of cancer patients and increased risk of death by all diseases and oncological causes has been established. Mortality increases with the growth of the smoking intensity, i.e. the number of cigarettes, smoked per day. Smoking is associated with the worst general and oncological survivability. The statistically trend-line between the smoking intensity and survivability was observed: each additional unit of cigarette consumption (pack/year) leads to the Overall Survival Reduction by 1% (p = 0.002). The link between smoking and the risk of developing second primary tumors has been confirmed. Smoking increases the likelihood of side effects of the antitumor therapy both drug therapy and radiation therapy and reduces the treatment efficacy. The smoking cessation leads to a significant improvement in the prognosis of a cancer patient. Scientific data on the negative effect of smoking on the prognosis of cancer patients have a major clinical importance. The treatment program for cancer patients should include science-based methods for the smoking cessation. The latter is fundamentally important, taking into account that the smoking frequency among cancer patients is much higher than in the population.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

scholarly journals The effect of adjuvant radiotherapy on overall survival in adults with intracranial ependymoma

2019 ◽  
Vol 7 (4) ◽  
pp. 391-399
Author(s):  
Roshan S Prabhu ◽  
Christopher D Corso ◽  
Matthew C Ward ◽  
John H Heinzerling ◽  
Reshika Dhakal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Propensity Score ◽  
Adjuvant Radiotherapy ◽  
Subtotal Resection ◽  
National Cancer Database ◽  
Risk Of Death ◽  
Increased Risk ◽  
Intracranial Ependymoma ◽  
Male Sex ◽  
Grade 3

Abstract Background Adult intracranial ependymoma is rare, and the role for adjuvant radiotherapy (RT) is not well defined. Methods We used the National Cancer Database (NCDB) to select adults (age ≥ 22 years) with grade 2 to 3 intracranial ependymoma status postresection between 2004 and 2015 and treated with adjuvant RT vs observation. Four cohorts were generated: (1) all patients, (2) grade 2 only, (3) grade 2 status post–subtotal resection only, (4) and grade 3 only. The association between adjuvant RT use and overall survival (OS) was assessed using multivariate Cox and propensity score matched analyses. Results A total of 1787 patients were included in cohort 1, of which 856 patients (48%) received adjuvant RT and 931 (52%) were observed. Approximately two-thirds of tumors were supratentorial and 80% were grade 2. Cohorts 2, 3, and 4 included 1471, 345, and 316 patients, respectively. There was no significant association between adjuvant RT use and OS in multivariate or propensity score matched analysis in any of the cohorts. Older age, male sex, urban location, higher comorbidity score, earlier year of diagnosis, and grade 3 were associated with increased risk of death. Conclusions This large NCDB study did not demonstrate a significant association between adjuvant RT use and OS for adults with intracranial ependymoma, including for patients with grade 2 ependymoma status post–subtotal resection. The conflicting results regarding the efficacy of adjuvant RT in this patient population highlight the need for high-quality studies to guide therapy recommendations in adult ependymoma.

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