scholarly journals Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jingsong Zhang ◽  
Yang Zhang ◽  
Jun-Yan Kang ◽  
Shuiye Chen ◽  
Yongqun He ◽  
...  
Keyword(s):  
United Kingdom ◽  
Viral Replication ◽  
Viral Genome ◽  
Immune Escape ◽  
Alternative Hypothesis ◽  
Evolutionary Process ◽  
Human Populations ◽  
Whole Genome ◽  
Genome Sequences ◽  
The United Kingdom

AbstractThe presence of SARS-CoV-2 mutants, including the emerging variant B.1.1.7, has raised great concerns in terms of pathogenesis, transmission, and immune escape. Characterizing SARS-CoV-2 mutations, evolution, and effects on infectivity and pathogenicity is crucial to the design of antibody therapies and surveillance strategies. Here, we analyzed 454,443 SARS-CoV-2 spike genes/proteins and 14,427 whole-genome sequences. We demonstrated that the early variant B.1.1.7 may not have evolved spontaneously in the United Kingdom or within human populations. Our extensive analyses suggested that Canidae, Mustelidae or Felidae, especially the Canidae family (for example, dog) could be a possible host of the direct progenitor of variant B.1.1.7. An alternative hypothesis is that the variant was simply yet to be sampled. Notably, the SARS-CoV-2 whole-genome represents a large number of potential co-mutations. In addition, we used an experimental SARS-CoV-2 reporter replicon system to introduce the dominant co-mutations NSP12_c14408t, 5′UTR_c241t, and NSP3_c3037t into the viral genome, and to monitor the effect of the mutations on viral replication. Our experimental results demonstrated that the co-mutations significantly attenuated the viral replication. The study provides valuable clues for discovering the transmission chains of variant B.1.1.7 and understanding the evolutionary process of SARS-CoV-2.

scholarly journals Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2

2021 ◽  
Author(s):  
Jingsong Zhang ◽  
Yang Zhang ◽  
Junyan Kang ◽  
Shuiye Chen ◽  
Yongqun He ◽  
...  
Keyword(s):  
Viral Replication ◽  
Viral Genome ◽  
Immune Escape ◽  
Alternative Hypothesis ◽  
Evolutionary Process ◽  
P Value ◽  
Human Populations ◽  
Whole Genome ◽  
Genome Sequences ◽  
The United Kingdom

The presence of SARS-CoV-2 mutants, including the emerging variant B.1.1.7, has raised great concerns in terms of pathogenesis, transmission, and immune escape. Characterizing SARS-CoV-2 mutations, evolution, and effects on infectivity and pathogenicity is crucial to the design of antibody therapies and surveillance strategies. Here we analyzed 454,443 SARS-CoV-2 spike genes/proteins and 14,427 whole-genome sequences. We demonstrated that the early variant B.1.1.7 may not have evolved spontaneously in the United Kingdom or within human populations. Our extensive analyses suggested that Canidae, Mustelidae or Felidae, especially the Canidae family (for example, dog) could be a possible host of the direct progenitor of variant B.1.1.7. An alternative hypothesis is that the variant was simply yet to be sampled. Notably, the SARS-CoV-2 whole genome represents a large number of potential co-mutations with very strong statistical significances (p value<E-44). In addition, we used an experimental SARS-CoV-2 reporter replicon system to introduce the dominant co-mutations NSP12_c14408t, 5'UTR_c241t, and NSP3_c3037t into the viral genome, and to monitor the effect of the mutations on viral replication. Our experimental results demonstrated that the co-mutations significantly enhanced the viral replication. The study provides valuable clues for discovering the transmission chains of variant B.1.1.7 and understanding the evolutionary process of SARS-CoV-2.

scholarly journals Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018

2019 ◽  
Vol 24 (10) ◽  
Author(s):  
David W Eyre ◽  
Katy Town ◽  
Teresa Street ◽  
Leanne Barker ◽  
Nicholas Sanderson ◽  
...  
Keyword(s):  
United Kingdom ◽  
Neisseria Gonorrhoeae ◽  
Whole Genome ◽  
Drug Resistant ◽  
Genome Sequences ◽  
Sexual Network ◽  
The United Kingdom ◽  
Intermediate Resistance ◽  
Azithromycin Resistance ◽  
Urgent Action

We describe detection in the United Kingdom (UK) of the drug-resistant Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate azithromycin resistance. Two female patients developed infection following contact with UK-resident men from the same sexual network linked to travel to Ibiza, Spain. One case failed treatment with ceftriaxone, and azithromycin and gentamicin, before successful treatment with ertapenem. Both isolates had indistinguishable whole-genome sequences. Urgent action is essential to contain this drug-resistant strain.

scholarly journals SARS-CoV-2 within-host diversity and transmission

Science ◽  
2021 ◽  
Vol 372 (6539) ◽  
pp. eabg0821 ◽  
Author(s):  
Katrina A. Lythgoe ◽  
Matthew Hall ◽  
Luca Ferretti ◽  
Mariateresa de Cesare ◽  
George MacIntyre-Cockett ◽  
...  
Keyword(s):  
United Kingdom ◽  
Severe Acute Respiratory Syndrome ◽  
Phylogenetic Tree ◽  
Immune Escape ◽  
Clinical Samples ◽  
Diversity Patterns ◽  
Host Diversity ◽  
Viral Loads ◽  
The United Kingdom ◽  
Low Levels

Extensive global sampling and sequencing of the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have enabled researchers to monitor its spread and to identify concerning new variants. Two important determinants of variant spread are how frequently they arise within individuals and how likely they are to be transmitted. To characterize within-host diversity and transmission, we deep-sequenced 1313 clinical samples from the United Kingdom. SARS-CoV-2 infections are characterized by low levels of within-host diversity when viral loads are high and by a narrow bottleneck at transmission. Most variants are either lost or occasionally fixed at the point of transmission, with minimal persistence of shared diversity, patterns that are readily observable on the phylogenetic tree. Our results suggest that transmission-enhancing and/or immune-escape SARS-CoV-2 variants are likely to arise infrequently but could spread rapidly if successfully transmitted.

scholarly journals High-Resolution Analysis by Whole-Genome Sequencing of an International Lineage (Sequence Type 111) of Pseudomonas aeruginosa Associated with Metallo-Carbapenemases in the United Kingdom

2015 ◽  
Vol 53 (8) ◽  
pp. 2622-2631 ◽  
Author(s):  
Jane F. Turton ◽  
Laura Wright ◽  
Anthony Underwood ◽  
Adam A. Witney ◽  
Yuen-Ting Chan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
United Kingdom ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Sequence Type ◽  
Polymorphism Analysis ◽  
Whole Genome ◽  
Evolutionary Analysis ◽  
Accessory Gene ◽  
The United Kingdom

Whole-genome sequencing (WGS) was carried out on 87 isolates of sequence type 111 (ST-111) of Pseudomonas aeruginosa collected between 2005 and 2014 from 65 patients and 12 environmental isolates from 24 hospital laboratories across the United Kingdom on an Illumina HiSeq instrument. Most isolates (73) carried VIM-2, but others carried IMP-1 or IMP-13 (5) or NDM-1 (1); one isolate had VIM-2 and IMP-18, and 7 carried no metallo-beta-lactamase (MBL) gene. Single nucleotide polymorphism analysis divided the isolates into distinct clusters; the NDM-1 isolate was an outlier, and the IMP isolates and 6/7 MBL-negative isolates clustered separately from the main set of 73 VIM-2 isolates. Within the VIM-2 set, there were at least 3 distinct clusters, including a tightly clustered set of isolates from 3 hospital laboratories consistent with an outbreak from a single introduction that was quickly brought under control and a much broader set dominated by isolates from a long-running outbreak in a London hospital likely seeded from an environmental source, requiring different control measures; isolates from 7 other hospital laboratories in London and southeast England were also included. Bayesian evolutionary analysis indicated that all the isolates shared a common ancestor dating back ∼50 years (1960s), with the main VIM-2 set separating approximately 20 to 30 years ago. Accessory gene profiling revealed blocks of genes associated with particular clusters, with some having high similarity (≥95%) to bacteriophage genes. WGS of widely found international lineages such as ST-111 provides the necessary resolution to inform epidemiological investigations and intervention policies.

scholarly journals Whole genome sequences are required to fully resolve the linkage disequilibrium structure of human populations

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Reuben J. Pengelly ◽  
William Tapper ◽  
Jane Gibson ◽  
Marcin Knut ◽  
Rick Tearle ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Human Populations ◽  
Whole Genome ◽  
Linkage Disequilibrium Structure ◽  
Genome Sequences

scholarly journals Within-Host Variations of Human Papillomavirus Reveal APOBEC Signature Mutagenesis in the Viral Genome

2018 ◽  
Vol 92 (12) ◽  
pp. e00017-18 ◽  
Author(s):  
Yusuke Hirose ◽  
Mamiko Onuki ◽  
Yuri Tenjimbayashi ◽  
Seiichiro Mori ◽  
Yoshiyuki Ishii ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Cervical Cancer ◽  
Deep Sequencing ◽  
Viral Genome ◽  
Reference Sequence ◽  
Characteristic Change ◽  
Whole Genome ◽  
Cervical Carcinogenesis ◽  
Genome Sequences ◽  
Host Genetic

ABSTRACTPersistent infection with oncogenic human papillomaviruses (HPVs) causes cervical cancer, accompanied by the accumulation of somatic mutations into the host genome. There are concomitant genetic changes in the HPV genome during viral infection; however, their relevance to cervical carcinogenesis is poorly understood. Here, we explored within-host genetic diversity of HPV by performing deep-sequencing analyses of viral whole-genome sequences in clinical specimens. The whole genomes of HPV types 16, 52, and 58 were amplified by type-specific PCR from total cellular DNA of cervical exfoliated cells collected from patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) and were deep sequenced. After constructing a reference viral genome sequence for each specimen, nucleotide positions showing changes with >0.5% frequencies compared to the reference sequence were determined for individual samples. In total, 1,052 positions of nucleotide variations were detected in HPV genomes from 151 samples (CIN1,n= 56; CIN2/3,n= 68; ICC,n= 27), with various numbers per sample. Overall, C-to-T and C-to-A substitutions were the dominant changes observed across all histological grades. While C-to-T transitions were predominantly detected in CIN1, their prevalence was decreased in CIN2/3 and fell below that of C-to-A transversions in ICC. Analysis of the trinucleotide context encompassing substituted bases revealed that TpCpN, a preferred target sequence for cellular APOBEC cytosine deaminases, was a primary site for C-to-T substitutions in the HPV genome. These results strongly imply that the APOBEC proteins are drivers of HPV genome mutation, particularly in CIN1 lesions.IMPORTANCEHPVs exhibit surprisingly high levels of genetic diversity, including a large repertoire of minor genomic variants in each viral genotype. Here, by conducting deep-sequencing analyses, we show for the first time a comprehensive snapshot of the within-host genetic diversity of high-risk HPVs during cervical carcinogenesis. Quasispecies harboring minor nucleotide variations in viral whole-genome sequences were extensively observed across different grades of CIN and cervical cancer. Among the within-host variations, C-to-T transitions, a characteristic change mediated by cellular APOBEC cytosine deaminases, were predominantly detected throughout the whole viral genome, most strikingly in low-grade CIN lesions. The results strongly suggest that within-host variations of the HPV genome are primarily generated through the interaction with host cell DNA-editing enzymes and that such within-host variability is an evolutionary source of the genetic diversity of HPVs.

scholarly journals Tracking human population structure through time from whole genome sequences

2019 ◽  
Author(s):  
Ke Wang ◽  
Iain Mathieson ◽  
Jared O’Connell ◽  
Stephan Schiffels
Keyword(s):  
Population Structure ◽  
Gene Flow ◽  
Demographic History ◽  
Time Dependent ◽  
Human Populations ◽  
Whole Genome ◽  
Genome Sequences ◽  
Migration Model ◽  
Novel Approach ◽  
Different Populations

AbstractThe genetic diversity of humans, like many species, has been shaped by a complex pattern of population separations followed by isolation and subsequent admixture. This pattern, reaching at least as far back as the appearance of our species in the paleontological record, has left its traces in our genomes. Reconstructing a population’s history from these traces is a challenging problem. Here we present a novel approach based on the Multiple Sequentially Markovian Coalescent (MSMC) to analyse the population separation history. Our approach, called MSMC-IM, uses an improved implementation of the MSMC (MSMC2) to estimate coalescence rates within and across pairs of populations, and then fits a continuous Isolation-Migration model to these rates to obtain a time-dependent estimate of gene flow. We show, using simulations, that our method can identify complex demographic scenarios involving post-split admixture or archaic introgression. We apply MSMC-IM to whole genome sequences from 15 worldwide populations, tracking the process of human genetic diversification. We detect traces of extremely deep ancestry between some African populations, with around 1% of ancestry dating to divergences older than a million years ago.Author SummaryHuman demographic history is reflected in specific patterns of shared mutations between the genomes from different populations. Here we aim to unravel this pattern to infer population structure through time with a new approach, called MSMC-IM. Based on estimates of coalescence rates within and across populations, MSMC-IM fits a time-dependent migration model to the pairwise rate of coalescences. We implemented this approach as an extension to existing software (MSMC2), and tested it with simulations exhibiting different histories of admixture and gene flow. We then applied it to the genomes from 15 worldwide populations to reveal their pairwise separation history ranging from a few thousand up to several million years ago. Among other results, we find evidence for remarkably deep population structure in some African population pairs, suggesting that deep ancestry dating to one million years ago and older is still present in human populations in small amounts today.

scholarly journals Genome Sequences of Equine Herpesvirus 1 Strains from a European Outbreak of Neurological Disorders Linked to a Horse Gathering in Valencia, Spain, in 2021

2021 ◽  
Vol 10 (20) ◽  
Author(s):  
Nick Vereecke ◽  
Flora Carnet ◽  
Stéphane Pronost ◽  
Katleen Vanschandevijl ◽  
Sebastiaan Theuns ◽  
...  
Keyword(s):  
United Kingdom ◽  
Neurological Disorders ◽  
Common Source ◽  
Equine Herpesvirus ◽  
Genome Sequences ◽  
Equine Herpesvirus 1 ◽  
Source Of Infection ◽  
The United Kingdom ◽  
Herpesvirus 1

ABSTRACT Five equine herpesvirus 1 (EHV-1) genome sequences with links to an EHV-1 outbreak with neurological disorders after a horse gathering in Valencia, Spain, in February 2021, were determined. All strains showed the closest relationships to strains from Belgium and the United Kingdom, indicating a common source of infection.

scholarly journals Draft Whole-Genome Sequence of a Haemophilus quentini Strain Isolated from an Infant in the United Kingdom

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Alasdair T. M. Hubbard ◽  
Sian E. W. Davies ◽  
Laura Baxter ◽  
Sarah Thompson ◽  
Mark M. Collery ◽  
...  
Keyword(s):  
United Kingdom ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Genome Sequence ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
The United Kingdom ◽  
Tract Infections

Haemophilus quentini is a rare and distinct genospecies of Haemophilus that has been suggested as a cause of neonatal bacteremia and urinary tract infections in men. We present the draft whole-genome sequence of H. quentini MP1 isolated from an infant in the United Kingdom, aiding future identification and detection of this pathogen.

Identification of a canine coronavirus in Australian racing Greyhounds

2021 ◽  
pp. 104063872110548
Author(s):  
Craig S. Smith ◽  
Martin F. Lenz ◽  
Karen Caldwell ◽  
Jane Oakey
Keyword(s):  
United Kingdom ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Gastrointestinal Disease ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Enteric Disease ◽  
The United Kingdom ◽  
Canine Coronavirus ◽  
Coronavirus Infection

Coronavirus infection can cause a range of syndromes, which in dogs can include mild-to-severe enteritis that generally resolves rapidly. Fatalities can occur from coinfection with other pathogens, including canine parvovirus. Between late December 2019 and April 2020, canine coronavirus (CCoV) was detected in Australian racing Greyhounds that displayed signs of gastrointestinal disease. The CCoV was genotyped using high-throughput sequencing, recovering 98.3% of a type IIb CCoV, generally thought to cause a mild but highly contagious enteric disease. The Australian CCoV was almost identical (99.9%, whole-genome sequence) to another CCoV associated with an outbreak of severe vomiting in dogs in the United Kingdom at the same time (December 2019–March 2020).

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