scholarly journals Initial Insights Into the Genetic Epidemiology of SARS-CoV-2 Isolates From Kerala Suggest Local Spread From Limited Introductions

2021 ◽  
Vol 12 ◽  
Author(s):  
Chandni Radhakrishnan ◽  
Mohit Kumar Divakar ◽  
Abhinav Jain ◽  
Prasanth Viswanathan ◽  
Rahul C. Bhoyar ◽  
...  
Keyword(s):  
Genetic Epidemiology ◽  
Binding Sites ◽  
Haplotype Analysis ◽  
Rt Pcr ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Functional Variants ◽  
Local Spread ◽  
Novel Variants ◽  
The World

Coronavirus disease 2019 (COVID-19) rapidly spread from a city in China to almost every country in the world, affecting millions of individuals. The rapid increase in the COVID-19 cases in the state of Kerala in India has necessitated the understanding of SARS-CoV-2 genetic epidemiology. We sequenced 200 samples from patients in Kerala using COVIDSeq protocol amplicon-based sequencing. The analysis identified 166 high-quality single-nucleotide variants encompassing four novel variants and 89 new variants in the Indian isolated SARS-CoV-2. Phylogenetic and haplotype analysis revealed that the virus was dominated by three distinct introductions followed by local spread suggesting recent outbreaks and that it belongs to the A2a clade. Further analysis of the functional variants revealed that two variants in the S gene associated with increased infectivity and five variants mapped in primer binding sites affect the efficacy of RT-PCR. To the best of our knowledge, this is the first and most comprehensive report of SARS-CoV-2 genetic epidemiology from Kerala.

scholarly journals Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions

2020 ◽  
Author(s):  
Chandni Radhakrishnan ◽  
Mohit Kumar Divakar ◽  
Abhinav Jain ◽  
Prasanth Viswanathan ◽  
Rahul C. Bhoyar ◽  
...  
Keyword(s):  
Genetic Epidemiology ◽  
Haplotype Analysis ◽  
Tertiary Hospital ◽  
Rt Pcr ◽  
Functional Variants ◽  
Local Spread ◽  
First Case ◽  
Novel Variants ◽  
The World ◽  
First Time

ABSTRACTCoronavirus disease 2019 (COVID-19) rapidly spread from a city in China to almost every country in the world, affecting millions of individuals. Genomic approaches have been extensively used to understand the evolution and epidemiology of SARS-CoV-2 across the world. Kerala is a unique state in India well connected with the rest of the world through a large number of expatriates, trade, and tourism. The first case of COVID-19 in India was reported in Kerala in January 2020, during the initial days of the pandemic. The rapid increase in the COVID-19 cases in the state of Kerala has necessitated the understanding of the genetic epidemiology of circulating virus, evolution, and mutations in SARS-CoV-2. We sequenced a total of 200 samples from patients at a tertiary hospital in Kerala using COVIDSeq protocol at a mean coverage of 7,755X. The analysis identified 166 unique high-quality variants encompassing 4 novel variants and 89 new variants identified for the first time in SARS-CoV-2 samples isolated from India. Phylogenetic and haplotype analysis revealed that the circulating population of the virus was dominated (94.6% of genomes) by three distinct introductions followed by local spread, apart from identifying polytomies suggesting recent outbreaks. The genomes formed a monophyletic distribution exclusively mapping to the A2a clade. Further analysis of the functional variants revealed two variants in the S gene of the virus reportedly associated with increased infectivity and 5 variants that mapped to five primer/probe binding sites that could potentially compromise the efficacy of RT-PCR detection. To the best of our knowledge, this is the first and most comprehensive report of genetic epidemiology and evolution of SARS-CoV-2 isolates from Kerala.

scholarly journals Prediction of genome-wide effects of single nucleotide variants on transcription factor binding

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sebastian Carrasco Pro ◽  
Katia Bulekova ◽  
Brian Gregor ◽  
Adam Labadorf ◽  
Juan Ignacio Fuxman Bass
Keyword(s):  
Binding Sites ◽  
Cancer Type ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Regulatory Regions ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Gene Regulatory ◽  
The Impact ◽  
The Relationship

Abstract Single nucleotide variants (SNVs) located in transcriptional regulatory regions can result in gene expression changes that lead to adaptive or detrimental phenotypic outcomes. Here, we predict gain or loss of binding sites for 741 transcription factors (TFs) across the human genome. We calculated ‘gainability’ and ‘disruptability’ scores for each TF that represent the likelihood of binding sites being created or disrupted, respectively. We found that functional cis-eQTL SNVs are more likely to alter TF binding sites than rare SNVs in the human population. In addition, we show that cancer somatic mutations have different effects on TF binding sites from different TF families on a cancer-type basis. Finally, we discuss the relationship between these results and cancer mutational signatures. Altogether, we provide a blueprint to study the impact of SNVs derived from genetic variation or disease association on TF binding to gene regulatory regions.

scholarly journals Rapid base-specific calling of SARS-CoV-2 variants of concern using combined RT-PCR melting curve screening and SIRPH technology

2021 ◽  
Author(s):  
Sascha Tierling ◽  
Kathrin Kattler ◽  
Markus Vogelgesang ◽  
Thorsten Pfuhl ◽  
Stefan Lohse ◽  
...  
Keyword(s):  
Melting Curve ◽  
Curve Analysis ◽  
Melting Curve Analysis ◽  
Rt Pcr ◽  
Single Nucleotide ◽  
Specific Identification ◽  
Rp Hplc ◽  
Novel Variants ◽  
Reliable Detection ◽  
Cost Efficient

The emergence of novel variants of concern of SARS-CoV-2 demands a fast and reliable detection of such variants in local populations. Here we present a cost-efficient and fast workflow combining a pre-screening of SARS-CoV-2 positive samples using RT-PCR melting curve analysis with multiplexed IP-RP-HPLC-based single nucleotide primer extensions (SIRPH). The entire workflow from positive SARS-CoV-2 testing to base-specific identification of variants requires about 24 h. We applied the sensitive method to monitor the local VOC outbreaks in a few hundred positive samples collected in a confined region of Germany.

scholarly journals Discovery of human ACE2 variants with altered recognition by the SARS-CoV-2 spike protein

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251585
Author(s):  
Pete Heinzelman ◽  
Philip A. Romero
Keyword(s):  
Clinical Trial ◽  
Genetic Variants ◽  
Trial Design ◽  
Clinical Trial Design ◽  
Spike Protein ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Novel Variants ◽  
The Future ◽  
Fundamental Research

Understanding how human ACE2 genetic variants differ in their recognition by SARS-CoV-2 can facilitate the leveraging of ACE2 as an axis for treating and preventing COVID-19. In this work, we experimentally interrogate thousands of ACE2 mutants to identify over one hundred human single-nucleotide variants (SNVs) that are likely to have altered recognition by the virus, and make the complementary discovery that ACE2 residues distant from the spike interface influence the ACE2-spike interaction. These findings illuminate new links between ACE2 sequence and spike recognition, and could find substantial utility in further fundamental research that augments epidemiological analyses and clinical trial design in the contexts of both existing strains of SARS-CoV-2 and novel variants that may arise in the future.

scholarly journals GESS: a database of global evaluation of SARS-CoV-2/hCoV-19 sequences

2020 ◽  
Vol 49 (D1) ◽  
pp. D706-D714 ◽  
Author(s):  
Shuyi Fang ◽  
Kailing Li ◽  
Jikui Shen ◽  
Sheng Liu ◽  
Juli Liu ◽  
...  
Keyword(s):  
Genomic Region ◽  
Comprehensive Analysis ◽  
Mutation Rates ◽  
Global Evaluation ◽  
Single Nucleotide Variants ◽  
High Coverage ◽  
Single Nucleotide ◽  
Genomic Variations ◽  
Area Of Interest ◽  
The World

Abstract The COVID-19 outbreak has become a global emergency since December 2019. Analysis of SARS-CoV-2 sequences can uncover single nucleotide variants (SNVs) and corresponding evolution patterns. The Global Evaluation of SARS-CoV-2/hCoV-19 Sequences (GESS, https://wan-bioinfo.shinyapps.io/GESS/) is a resource to provide comprehensive analysis results based on tens of thousands of high-coverage and high-quality SARS-CoV-2 complete genomes. The database allows user to browse, search and download SNVs at any individual or multiple SARS-CoV-2 genomic positions, or within a chosen genomic region or protein, or in certain country/area of interest. GESS reveals geographical distributions of SNVs around the world and across the states of USA, while exhibiting time-dependent patterns for SNV occurrences which reflect development of SARS-CoV-2 genomes. For each month, the top 100 SNVs that were firstly identified world-widely can be retrieved. GESS also explores SNVs occurring simultaneously with specific SNVs of user's interests. Furthermore, the database can be of great help to calibrate mutation rates and identify conserved genome regions. Taken together, GESS is a powerful resource and tool to monitor SARS-CoV-2 migration and evolution according to featured genomic variations. It provides potential directive information for prevalence prediction, related public health policy making, and vaccine designs.

scholarly journals Genetic Screening of Plasticity Regulating Nogo-Type Signaling Genes in Migraine

2019 ◽  
Vol 10 (1) ◽  
pp. 5
Author(s):  
Gabriella Smedfors ◽  
Franziska Liesecke ◽  
Caroline Ran ◽  
Lars Olson ◽  
Tobias E. Karlsson ◽  
...  
Keyword(s):  
Genetic Screening ◽  
Grey Matter ◽  
Haplotype Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Haplotype Blocks ◽  
The World ◽  
Prevalent Disease ◽  
Potential Link ◽  
Subcortical Regions

Migraine is the sixth most prevalent disease in the world and a substantial number of experiments have been conducted to analyze potential differences between the migraine brain and the healthy brain. Results from these investigations point to the possibility that development and aggravation of migraine may include grey matter plasticity. Nogo-type signaling is a potent plasticity regulating system in the CNS and consists of ligands, receptors, co-receptors and modulators with a dynamic age- and activity-related expression in cortical and subcortical regions. Here we investigated a potential link between migraine and five key Nogo-type signaling genes: RTN4, OMGP, MAG, RTN4R and LINGO1, by screening 15 single nucleotide polymorphisms (SNPs) within these genes. In a large Swedish migraine cohort (749 migraine patients and 4032 controls), using a logistic regression with sex as covariate, we found that there was no such association. In addition, a haplotype analysis was performed which revealed three haplotype blocks. These blocks had no significant association with migraine. However, to robustly conclude that Nogo-type genotypes signaling do not influence the prevalence of migraine, further studies are encouraged.

scholarly journals Deep sequencing of 10,000 human genomes

2016 ◽  
Vol 113 (42) ◽  
pp. 11901-11906 ◽  
Author(s):  
Amalio Telenti ◽  
Levi C. T. Pierce ◽  
William H. Biggs ◽  
Julia di Iulio ◽  
Emily H. M. Wong ◽  
...  
Keyword(s):  
Reference Genome ◽  
Confidence Region ◽  
Single Nucleotide Variants ◽  
High Confidence ◽  
Single Nucleotide ◽  
Human Genomes ◽  
Exon Sequence ◽  
Novel Variants ◽  
Novel Variant ◽  
Individual Human

We report on the sequencing of 10,545 human genomes at 30×–40× coverage with an emphasis on quality metrics and novel variant and sequence discovery. We find that 84% of an individual human genome can be sequenced confidently. This high-confidence region includes 91.5% of exon sequence and 95.2% of known pathogenic variant positions. We present the distribution of over 150 million single-nucleotide variants in the coding and noncoding genome. Each newly sequenced genome contributes an average of 8,579 novel variants. In addition, each genome carries on average 0.7 Mb of sequence that is not found in the main build of the hg38 reference genome. The density of this catalog of variation allowed us to construct high-resolution profiles that define genomic sites that are highly intolerant of genetic variation. These results indicate that the data generated by deep genome sequencing is of the quality necessary for clinical use.

scholarly journals Rapid base-specific calling of SARS-CoV-2 variants of concern using combined RT-PCR melting curve screening and SIRPH technology

2021 ◽  
Author(s):  
Sascha Tierling ◽  
Kathrin Kattler ◽  
Markus Vogelgesang ◽  
Thorsten Pfuhl ◽  
Stefan Lohse ◽  
...  
Keyword(s):  
Melting Curve ◽  
Curve Analysis ◽  
Melting Curve Analysis ◽  
Rt Pcr ◽  
Single Nucleotide ◽  
Specific Identification ◽  
Rp Hplc ◽  
Novel Variants ◽  
Reliable Detection ◽  
Cost Efficient

Abstract The emergence of novel variants of concern of SARS-CoV-2 demands a fast and reliable detection of such variants in local populations. Here we present a cost-efficient and fast workflow combining a pre-screening of SARS-CoV-2 positive samples using RT-PCR melting curve analysis with multiplexed IP-RP-HPLC-based single nucleotide primer extensions (SIRPH). The entire workflow from positive SARS-CoV-2 testing to base-specific identification of variants requires about 24 h. We applied the sensitive method to monitor the local VOC outbreaks in SARS-CoV-2 positive samples collected in a confined region of Germany.

scholarly journals qPCR assays with dual-labeled probes for genotyping honey bee variants associated with varroa resistance

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
David Claeys Boúúaert ◽  
Mario Van Poucke ◽  
Lina De Smet ◽  
Wim Verbeke ◽  
Dirk C. de Graaf ◽  
...  
Keyword(s):  
Honey Bee ◽  
Honey Bees ◽  
Binding Sites ◽  
Varroa Mite ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Breeding Programs ◽  
Mite Reproduction ◽  
Varroa Resistance ◽  
Development And Validation

Abstract Background The varroa mite is one of the main causes of honey bee mortality. An important mechanism by which honey bees increase their resistance against this mite is the expression of suppressed mite reproduction. This trait describes the physiological inability of mites to produce viable offspring and was found associated with eight genomic variants in previous research. Results This paper presents the development and validation of high-throughput qPCR assays with dual-labeled probes for discriminating these eight single-nucleotide variants. Amplicon sequences used for assay validation revealed additional variants in the primer/probe binding sites in four out of the eight assays. As for two of these the additional variants interfered with the genotyping outcome supplementary primers and/or probes were developed. Inclusion of these primers and probes in the assay mixes allowed for the correct genotyping of all eight variants of interest within our bee population. Conclusion These outcomes underline the importance of checking for interfering variants in designing qPCR assays. Ultimately, the availability of this assay allows genotyping for the suppressed mite reproduction trait and paves the way for marker assisted selection in breeding programs.

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