scholarly journals Emergence of within-host SARS-CoV-2 recombinant genome after coinfection by Gamma and Delta variants

2021 ◽  
Author(s):  
Ronaldo da Silva Francisco Junior ◽  
Luiz G P de Almeida ◽  
Alessandra P Lamarca ◽  
Liliane Cavalcante ◽  
Yasmmin Martins ◽  
...  
Keyword(s):  
Health Management ◽  
Rna Recombination ◽  
Rna Sequences ◽  
Spike Gene ◽  
Nucleocapsid Gene ◽  
First Case ◽  
Novel Variants ◽  
Recombinant Genome ◽  
Generation Sequencing ◽  
Genomic Similarity

Abstract Since the first reports of patients coinfected by two genetically-distinct lineages of SARS-CoV-2, the scientific community raised concerns about the recombination of intra-host viral RNA sequences as a possible mechanism underlying the emergence of novel variants. Indeed, this phenomenon occurs at a relatively high frequency among betacoronaviruses. Nevertheless, the few existing studies about recombination between genetically-distinct lineages of SARS-CoV-2 are restricted to detect the inter-host dissemination of genomes post-recombination events. However, the high genomic similarity between the current co-circulating lineages challenges the identification of these events. Here, we report the first case of intra-host SARS-CoV-2 recombination during a coinfection by the variants of concern (VOC) AY.33 (Delta) and P.1 (Gamma) supported by sequencing reads harboring a mosaic of lineage-defining mutations. By using next-generation sequencing reads intersecting regions that simultaneously overlap lineage-defining mutations from Gamma and Delta, we were able to identify a total of six recombinant regions across the SARS-CoV-2 genome within a sample. Four of them mapped in the spike gene and two in the nucleocapsid gene. We detected mosaic reads harboring a combination of lineage-defining mutations from each VOC. To our knowledge, this is the first report of intra-host RNA-RNA recombination between two lineages of SARS-CoV-2, which can represent a threat to public health management during the COVID-19 pandemic due to the possibility of the emergence of viruses with recombinant phenotypes.

Epidemiology of HIV in Iran

2020 ◽  
Vol 18 (4) ◽  
pp. 228-236
Author(s):  
Zeinab Najafi ◽  
Leila Taj ◽  
Omid Dadras ◽  
Fatemeh Ghadimi ◽  
Banafsheh Moradmand ◽  
...  
Keyword(s):  
Middle East ◽  
Hiv Prevention ◽  
Prevention And Control ◽  
Hiv Transmission ◽  
Health Management ◽  
Key Populations ◽  
Mena Region ◽  
First Case ◽  
And Control ◽  
Hiv Aids

: Iran has been one of the active countries fighting against HIV/AIDS in the Middle East during the last decades. Moreover, there is a strong push to strengthen the national health management system concerning HIV prevention and control. In Iran, HIV disease has its unique features, from changes in modes of transmission to improvement in treatment and care programs, which can make it a good case for closer scrutiny. The present review describes the HIV epidemic in Iran from the first case diagnosed until prevention among different groups at risk and co-infections. Not only we addressed the key populations and community-based attempts to overcome HIV-related issues in clinics, but we also elaborated on the efforts and trends in society and the actual behaviors related to HIV/AIDS. Being located in the Middle East and North Africa (MENA) region, given the countryspecific characteristics, and despite all the national efforts along with other countries in this region, Iran still needs to take extra measures to reduce HIV transmission, especially in health education. Although Iran is one of the pioneers in implementing applicable and appropriate policies in the MENA region, including harm reduction services to reduce HIV incidence, people with substance use disorder continue to be the majority of those living with HIV in the country. Similar to other countries in this region, the HIV prevention and control programs aim at 90-90-90 targets to eliminate HIV infection and reduce the transmission, especially the mother-to-child transmission and among other key populations.

scholarly journals PATH-17. NOVEL DUAL HISTONE 3 K27M AND G34R POINT MUTATIONS IN A MIDLINE GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii167-ii167
Author(s):  
Peter Pan ◽  
Tejus Bale ◽  
Alexandra Miller ◽  
Marc Ladanyi ◽  
Marc Rosenblum ◽  
...  
Keyword(s):  
Point Mutations ◽  
Histone 3 ◽  
First Case ◽  
Microvascular Proliferation ◽  
Motor Neuron Facial Nerve ◽  
Methylguanine Methyltransferase ◽  
Mitotic Figures ◽  
In Cis ◽  
Generation Sequencing ◽  
Diffuse Midline Glioma

Abstract BACKGROUND Histone H3 alterations due to mutations on H3F3A and HIST1H3B genes, have in recent years been associated with distinct entities and tumor locations within the context of infiltrative gliomas. H3K27M is associated with a midline location and is included in the WHO 2016 as the diffuse midline glioma H3K27M-mutant, a specific diagnostic entity. H3G34R, thought to be a mutually exclusive alteration, is less common but has been associated with a cerebral hemispheric location. We report the first case to our knowledge with both of these alterations in the same tumor. METHODS Clinical and pathologic records of the patient were reviewed and presented. RESULTS A 39-year-old man presented with acute right face, arm, and leg numbness and mild weakness; examination was notable for right lower motor neuron facial nerve palsy and numbness, along with numbness and subtle slowing of rapid alternating movements in the left arm and leg. A non-enhancing left thalamic mass was identified and stereotactically biopsied. Infiltrative glial neoplasm with moderately-increased cellularity was seen, with ovoid cells, enlarged nuclei, apoptotic bodies, and mitotic figures. No necrosis or microvascular proliferation seen. Immunostain was positive for H3K27M. O6-methylguanine-methyltransferase (MGMT) promoter was not methylated. Next-generation sequencing showed dual in cis H3 point mutations in K27M (HIST1H3B c.83A >T) and G34R (HIST1H3B c.103G >C). Additional alterations were noted in NF1, PIK3CA, ATRX, FGFR3, and NSD1. Isocitrate dehydrogenase (IDH1/2) mutations were not identified. CONCLUSION This case of a young man with a midline glioma is novel for carrying both H3K27M and H3G34R alterations and indicates these alterations are not mutually exclusive. The interaction seen here suggests H3K27M dominance for a midline phenotype.

scholarly journals Emergence of novel SARS-CoV-2 variants in the Netherlands

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aysun Urhan ◽  
Thomas Abeel
Keyword(s):  
The Netherlands ◽  
Population Diversity ◽  
Genomic Variation ◽  
Population Variation ◽  
Reference Sequence ◽  
Viral Population ◽  
Phylogenetic Study ◽  
First Case ◽  
Novel Variants ◽  
Frequent Mutations

AbstractCoronavirus disease 2019 (COVID-19) has emerged in December 2019 when the first case was reported in Wuhan, China and turned into a pandemic with 27 million (September 9th) cases. Currently, there are over 95,000 complete genome sequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, in public databases, accompanying a growing number of studies. Nevertheless, there is still much to learn about the viral population variation when the virus is evolving as it continues to spread. We have analyzed SARS-CoV-2 genomes to identify the most variant sites, as well as the stable, conserved ones in samples collected in the Netherlands until June 2020. We identified the most frequent mutations in different geographies. We also performed a phylogenetic study focused on the Netherlands to detect novel variants emerging in the late stages of the pandemic and forming local clusters. We investigated the S and N proteins on SARS-CoV-2 genomes in the Netherlands and found the most variant and stable sites to guide development of diagnostics assays and vaccines. We observed that while the SARS-CoV-2 genome has accumulated mutations, diverging from reference sequence, the variation landscape is dominated by four mutations globally, suggesting the current reference does not represent the virus samples circulating currently. In addition, we detected novel variants of SARS-CoV-2 almost unique to the Netherlands that form localized clusters and region-specific sub-populations indicating community spread. We explored SARS-CoV-2 variants in the Netherlands until June 2020 within a global context; our results provide insight into the viral population diversity for localized efforts in tracking the transmission of COVID-19, as well as sequenced-based approaches in diagnostics and therapeutics. We emphasize that little diversity is observed globally in recent samples despite the increased number of mutations relative to the established reference sequence. We suggest sequence-based analyses should opt for a consensus representation to adequately cover the genomic variation observed to speed up diagnostics and vaccine design.

scholarly journals Tiled-ClickSeq for targeted sequencing of complete coronavirus genomes with simultaneous capture of RNA recombination and minority variants

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elizabeth Jaworski ◽  
Rose M Langsjoen ◽  
Brooke Mitchell ◽  
Barbara Judy ◽  
Patrick Newman ◽  
...  
Keyword(s):  
Full Range ◽  
Virus Genome ◽  
Clinical Samples ◽  
Rna Recombination ◽  
Single Nucleotide ◽  
Reverse Transcription Reaction ◽  
Minority Variants ◽  
Next Generation Sequencing Ngs ◽  
Unique Molecular Identifier ◽  
Generation Sequencing

High-throughput genomics of SARS-CoV-2 is essential to characterize virus evolution and to identify adaptations that affect pathogenicity or transmission. While single-nucleotide variations (SNVs) are commonly considered as driving virus adaption, RNA recombination events that delete or insert nucleic acid sequences are also critical. Whole genome targeting sequencing of SARS-CoV-2 is typically achieved using pairs of primers to generate cDNA amplicons suitable for next-generation sequencing (NGS). However, paired-primer approaches impose constraints on where primers can be designed, how many amplicons are synthesized and requires multiple PCR reactions with non-overlapping primer pools. This imparts sensitivity to underlying SNVs and fails to resolve RNA recombination junctions that are not flanked by primer pairs. To address these limitations, we have designed an approach called ‘Tiled-ClickSeq’, which uses hundreds of tiled-primers spaced evenly along the virus genome in a single reverse-transcription reaction. The other end of the cDNA amplicon is generated by azido-nucleotides that stochastically terminate cDNA synthesis, removing the need for a paired-primer. A sequencing adaptor containing a Unique Molecular Identifier (UMI) is appended to the cDNA fragment using click-chemistry and a PCR reaction generates a final NGS library. Tiled-ClickSeq provides complete genome coverage, including the 5’UTR, at high depth and specificity to the virus on both Illumina and Nanopore NGS platforms. Here, we analyze multiple SARS-CoV-2 isolates and clinical samples to simultaneously characterize minority variants, sub-genomic mRNAs (sgmRNAs), structural variants (SVs) and D-RNAs. Tiled-ClickSeq therefore provides a convenient and robust platform for SARS-CoV-2 genomics that captures the full range of RNA species in a single, simple assay.

scholarly journals Hormone receptor expression of colorectal cancer diagnosed during the peri-partum period

2019 ◽  
Vol 8 (8) ◽  
pp. 1149-1158 ◽  
Author(s):  
Jordyn Silverstein ◽  
Wesley Kidder ◽  
Susan Fisher ◽  
Thomas A Hope ◽  
Samantha Maisel ◽  
...  
Keyword(s):  
Significant Risk ◽  
Case Series ◽  
Stage Iv ◽  
Receptor Expression ◽  
Primary Tumors ◽  
Molecular Features ◽  
First Case ◽  
Hormone Receptor Expression ◽  
Generation Sequencing ◽  
Formalin Fixed

Background Colorectal carcinoma (CRC) during the peri-partum period is challenging to diagnose due to the overlapping symptoms of CRC and pregnancy. This is the first case series to investigate clinicopathologic, hormonal and molecular features of CRC diagnosed during the peri-partum period. We hypothesized that advanced presentations of CRC could possibly be mitigated by pregnancy-related hormonal factors. Methods We conducted a retrospective review of five women diagnosed with CRC during the peri-partum period and studied the clinical and molecular features of their cancer. Results All patients presented with stage IV CRC at diagnosis; three had primary tumors in the rectum and two had primary tumors in the sigmoid colon. The liver was the most common metastatic site (three of five women). Immunohistochemistry stains were negative for estrogen receptors alpha (ERα) and beta (ERβ), and one tumor demonstrated low-level positivity for PR (1%). Formalin-fixed and paraffin-embedded (FFPE) biopsies from each case were tested with next-generation sequencing and found that all tumors were mismatch repair (MMR) proficient, and three harbored a KRAS mutation. Germline testing showed no predisposition to CRC; however, several somatic variants of undetermined significance (VUS) were identified. Discussion CRC in the peri-partum period poses significant risk factors for presentations with advanced disease due to diagnostic challenges. While our study provides no evidence that pathogenesis of CRC during pregnancy is driven by elevated estrogen and/or progesterone levels during pregnancy, additional putative etiologic factors, including placental growth factors, the immunosuppressive state of pregnancy and other physiologic processes during pregnancy, warrant future study.

scholarly journals Congenital Oral Squamous Cell Carcinoma in a Suckling Piglet

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Jasmine Hattab ◽  
Abigail Rose Trachtman ◽  
Pietro Giorgio Tiscar ◽  
Marco Di Domenico ◽  
Jessica Maria Abbate ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lower Lip ◽  
Papillomavirus Infection ◽  
First Case ◽  
Suckling Piglet ◽  
Generation Sequencing ◽  
Histopathological Investigation

A 3-week-old suckling piglet spontaneously died after septicemic colibacillosis. At postmortem examination, bulging and ulcerated lesions were seen, affecting the oral mucosa on the inner surface of the lower lip. After histopathological investigation, the diagnosis of congenital oral squamous cell carcinoma was made. To the best of our knowledge, this is the first case of congenital oral squamous cell carcinoma ever described. A relationship has been shown or suggested between papillomavirus infection and oral squamous cell carcinoma in humans and animals. However, next-generation sequencing study did not demonstrate any papillomavirus sequences in the case reported herein.

scholarly journals Rapid metagenomic characterization of a case of imported COVID-19 in Cambodia

2020 ◽  
Author(s):  
Jessica E. Manning ◽  
Jennifer A. Bohl ◽  
Sreyngim Lay ◽  
Sophana Chea ◽  
Ly Sovann ◽  
...  
Keyword(s):  
Disease Outbreaks ◽  
Bioinformatics Pipeline ◽  
Illumina Platform ◽  
Resource Limited ◽  
First Case ◽  
Rapid Production ◽  
Public Health Information ◽  
Pathogen Genome ◽  
Generation Sequencing

AbstractRapid production and publication of pathogen genome sequences during emerging disease outbreaks provide crucial public health information. In resource-limited settings, especially near an outbreak epicenter, conventional deep sequencing or bioinformatics are often challenging. Here we successfully used metagenomic next generation sequencing on an iSeq100 Illumina platform paired with an open-source bioinformatics pipeline to quickly characterize Cambodia’s first case of COVID-2019.

Genetic Characterization of Hereditary Cancer Syndromes Based on Targeted Next-Generation Sequencing

2021 ◽  
pp. 1-9
Author(s):  
Pelin Ercoskun ◽  
Cigdem Yuce Kahraman ◽  
Guller Ozkan ◽  
Abdulgani Tatar
Keyword(s):  
Hereditary Cancer ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Novel Variants ◽  
Genetics And Genomics ◽  
Cancer Syndromes ◽  
Generation Sequencing

A hereditary cancer syndrome is a genetic predisposition to cancer caused by a germline mutation in cancer-related genes. Identifying the disease-causing variant is important for both the patient and relatives at risk in cancer families because this could be a guide in treatment and secondary cancer prevention. In this study, hereditary cancer panel harboring cancer-related genes was performed on MiSeq Illumina NGS system from peripheral blood samples. Sequencing files were fed into a cloud-based data analysis pipeline. Reportable variants were classified according to the American College of Medical Genetics and Genomics guidelines. Three hundred five individuals were included in the study. Different pathogenic/likely pathogenic variants were detected in 75 individuals. The majority of these variants were in the <i>MUTYH</i>, <i>BRCA2</i>, and <i>CHEK2</i> genes. Nine novel pathogenic/likely pathogenic variants were identified in <i>BRCA1</i>, <i>BRCA2</i>, <i>GALNT12</i>, <i>ATM</i>, <i>MLH1</i>, <i>MSH2</i>, <i>APC</i>, and <i>KIT</i> genes. We obtained interesting and novel variants which could be related to hereditary cancer, and this study confirmed that NGS is an indispensable method for the risk assessment in cancer families.

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