Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Alu retrotransposons and COVID-19 susceptibility and morbidity.

ABSTRACT: SARS-CoV-2 has spread rapidly across the world and is negatively impacting the global human population. COVID-19 patients display a wide variety of symptoms and clinical outcomes, including those attributed to genetic ancestry. Alu retrotransposons have played an important role in human evolution, and their variants influence host response to viral infection. Intronic Alus regulate gene expression through several mechanisms, including both genetic and epigenetic pathways. With respect to SARS-CoV-2, an intronic Alu within the ACE gene is hypothesized to be associated with COVID-19 susceptibility and morbidity. Here, we review specific Alu polymorphisms that are of particular interest when considering host response to SARS-CoV-2 infection, especially polymorphic Alu insertions in genes associated with immune response and coagulation/fibrinolysis cascade. We posit that additional research focused on Alu-related pathways could yield novel biomarkers capable of predicting clinical outcomes as well as patient-specific treatment strategies for COVID-19 and related infectious diseases.

SUBMITTER: Li M

PROVIDER: S-EPMC7779329 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Modeling the amplification dynamics of human Alu retrotransposons.

Project description:Retrotransposons have had a considerable impact on the overall architecture of the human genome. Currently, there are three lineages of retrotransposons (Alu, L1, and SVA) that are believed to be actively replicating in humans. While estimates of their copy number, sequence diversity, and levels of insertion polymorphism can readily be obtained from existing genomic sequence data and population sampling, a detailed understanding of the temporal pattern of retrotransposon amplification remains elusive. Here we pose the question of whether, using genomic sequence and population frequency data from extant taxa, one can adequately reconstruct historical amplification patterns. To this end, we developed a computer simulation that incorporates several known aspects of primate Alu retrotransposon biology and accommodates sampling effects resulting from the methods by which mobile elements are typically discovered and characterized. By modeling a number of amplification scenarios and comparing simulation-generated expectations to empirical data gathered from existing Alu subfamilies, we were able to statistically reject a number of amplification scenarios for individual subfamilies, including that of a rapid expansion or explosion of Alu amplification at the time of human-chimpanzee divergence.

| S-EPMC1239904 | biostudies-literature

Duplication, coclustering, and selection of human Alu retrotransposons.

Project description:Alu and L1 are families of non-LTR retrotransposons representing approximately equal 30% of the human genome. Genomic distributions of young Alu and L1 elements are quite similar, but over time, Alu densities in GC-rich DNA increase in comparison with L1 densities. Here we analyze two processes that may contribute to this phenomenon. First, DNA duplications in the human genome occur more frequently in Alu- and GC-rich than in AT-rich chromosomal regions. Second, most Alu elements tend to be coclustered with each other, but recently retroposed elements are likely to be inserted outside the existing clusters. These "stand-alone" elements appear to be rapidly eliminated from the genome. We also report that over time, the densities of recently retroposed Alu families on chromosome Y decline rapidly, whereas Alu densities on chromosome X increase relative to autosomal densities. We propose that these changes in the chromosomal proportions of Alu densities and the elimination of stand-alone Alus represent the same process of paternal Alu selection. We also propose that long-term Alu accumulation in GC-rich DNA is associated with DNA duplication initiated by elevated recombinogenic activities in Alu clusters.

| S-EPMC337042 | biostudies-literature

Abnormal thrombosis and neutrophil activation increase hospital-acquired sacral pressure injuries and morbidity in COVID-19 patients

Project description:Characterization of the transcriptional signatures of 771 human genes and 19 coronavirus genes in skin samples collected from the borders of hospital-acquired sacral pressure injuries (HASPIs) that developed in individuals with and without COVID-19. Samples included pressure ulcers from individuals without COVID-19 (10), pressure ulcers from individuals with COVID-19 (5), as well as pressure ulcers with thrombotic vasculopathy histopathology from individuals with COVID-19 (8).

2023-04-12 | GSE214647 | GEO

TDP-43 regulates transcription at protein-coding genes and Alu retrotransposons.

Project description:The 43-kDa transactive response DNA-binding protein (TDP-43) is an example of an RNA-binding protein that regulates RNA metabolism at multiple levels from transcription and splicing to translation. Its role in post-transcriptional RNA processing has been a primary focus of recent research, but its role in regulating transcription has been studied for only a few human genes. We characterized the effects of TDP-43 on transcription genome-wide and found that TDP-43 broadly affects transcription of protein-coding and noncoding RNA genes. Among protein-coding genes, the effects of TDP-43 were greatest for genes <30 thousand base pairs in length. Surprisingly, we found that the loss of TDP-43 resulted in increased evidence for transcription activity near repetitive Alu elements found within expressed genes. The highest densities of affected Alu elements were found in the shorter genes, whose transcription was most affected by TDP-43. Thus, in addition to its role in post-transcriptional RNA processing, TDP-43 plays a critical role in maintaining the transcriptional stability of protein-coding genes and transposable DNA elements.

| S-EPMC6899060 | biostudies-literature

Valuing COVID-19 Morbidity Risk Reductions.

Project description:Many economic analyses, including those that address the COVID-19 pandemic, focus on the value of averting deaths and do not include the value of averting nonfatal illnesses. Yet incorporating the value of averting nonfatal cases may change conclusions about the desirability of the policy. While per case values may be small, the number of nonfatal cases is often large, far outstripping the number of fatal cases. The value of averting nonfatal cases is also increasingly important in evaluating COVID-19 policy options as vaccine- and infection-related immunity and treatments reduce the case-fatality rate. Unfortunately, little valuation research is available that explicitly addresses COVID-19 morbidity. We describe and implement an approach for approximating the value of averting nonfatal illnesses or injuries and apply it to COVID-19 in the United States. We estimate gains from averting COVID-19 morbidity of about 0.01 quality-adjusted life year (QALY) per mild case averted, 0.02 QALY per severe case, and 3.15 QALYs per critical case. These gains translate into monetary values of about $5,300 per mild case, $11,000 per severe case, and $1.8 million per critical case. While these estimates are imprecise, they suggest the magnitude of the effects.

| S-EPMC9455599 | biostudies-literature

Reduced A-to-I editing of endogenous Alu RNAs in severe COVID-19 disease

Project description:Severe COVID-19 disease is associated with elevated inflammatory responses. One form of Aicardi-Goutières Syndrome caused by inactivating mutations in ADAR results in reduced A-to-I editing of endogenous double-stranded RNAs (dsRNAs), induction of IFNs, interferon-stimulated genes (ISGs), other inflammatory mediators, morbidity and mortality. Alu elements, ~10% of the human genome, are the most common A-to-I editing sites. Using leukocyte whole-genome RNA sequencing data, we find reduced A-to-I editing of Alu dsRNAs in patients with severe COVID-19 disease. Unedited Alu dsRNAs, but not edited Alu dsRNAs, are potent inducers of IRF and NF-kB transcriptional responses, IL6, IL8 and ISGs. Thus, decreased A-to-I editing that may lead to accumulation of unedited Alu dsRNAs and increased inflammatory responses, is associated with severe COVID-19 disease.

2021-03-05 | GSE168286 | GEO

CoViD-19 Susceptibility.

Project description:There have been over five million cases of infection with the second Corona virus to induce SARS (SARS-CoV2) and close to half a million deaths worldwide since the first report of Corona Virus Disease in late December 2019 (CoViD-19). Over two million CoViD-19 patients have recovered. The factors and variables that lead certain CoViD-19 patients to survive this otherwise aggressive and lethal viral infection are intensely researched, as is the development of productive anti-virals and of safe and effective vaccines. Several hypotheses invoke putative mutations of the ss-positive RNA SARS-CoV2 virus to states of stronger or weaker virulence and lethality. Other hypotheses propose that the patient's status of immunity, vitamin D level, Zinc deficiency or other physiological parameters determine how any given patient will effectively weather the viremia and the consequential multi-symptomatic CoViD-19. The initial cause - causa prima - underlying all the symptoms of CoViD-19 is infection of the host human cell by SARS-CoV2. The virus spike (S) protein finds its binding site, ACE2, widely distributed in all cells and tissues that potentially proffer CoViD-19 pathology. S consists of two subunits, S1 and S2, which are cleaved by the widely expressed transmembrane protease serine 2 (TMPRSS2) before the virus fuses to the plasma membrane and infects the cell. Current trends show that variant alleles resulting from single nucleotide polymorphisms (SNPs) of ACE2, and genetic variants of TMPRSS2, with putative distinct affinities for S clip, may determine a complex multi-factorial spectrum of SARS-CoV2 virulence across patients, and predict CoViD-19 susceptibility.

| S-EPMC7505245 | biostudies-literature

Cohort survey of healthcare workers with COVID-19 infection

Project description: Not available

| S-BSST563 | biostudies-other

Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor.

Project description:Cell differentiation is a central process in development and in cancer growth and dissemination. OCT4 (POU5F1) and NANOG are essential for cell stemness and pluripotency; yet, the mechanisms that regulate their expression remain largely unknown. Repetitive elements account for almost half of the Human Genome; still, their role in gene regulation is poorly understood. Here, we show that the dioxin receptor (AHR) leads to differentiation of human carcinoma cells through the transcriptional upregulation of Alu retrotransposons, whose RNA transcripts can repress pluripotency genes. Despite the genome-wide presence of Alu elements, we provide evidences that those located at the NANOG and OCT4 promoters bind AHR, are transcribed by RNA polymerase-III and repress NANOG and OCT4 in differentiated cells. OCT4 and NANOG repression likely involves processing of Alu-derived transcripts through the miRNA machinery involving the Microprocessor and RISC. Consistently, stable AHR knockdown led to basal undifferentiation, impaired Alus transcription and blockade of OCT4 and NANOG repression. We suggest that transcripts produced from AHR-regulated Alu retrotransposons may control the expression of stemness genes OCT4 and NANOG during differentiation of carcinoma cells. The control of discrete Alu elements by specific transcription factors may have a dynamic role in genome regulation under physiological and diseased conditions.

| S-EPMC4889919 | biostudies-literature

The Role of SINE-VNTR-Alu (SVA) Retrotransposons in Shaping the Human Genome.

Project description:Retrotransposons can alter the regulation of genes both transcriptionally and post-transcriptionally, through mechanisms such as binding transcription factors and alternative splicing of transcripts. SINE-VNTR-Alu (SVA) retrotransposons are the most recently evolved class of retrotransposable elements, found solely in primates, including humans. SVAs are preferentially found at genic, high GC loci, and have been termed "mobile CpG islands". We hypothesise that the ability of SVAs to mobilise, and their non-random distribution across the genome, may result in differential regulation of certain pathways. We analysed SVA distribution patterns across the human reference genome and identified over-representation of SVAs at zinc finger gene clusters. Zinc finger proteins are able to bind to and repress SVA function through transcriptional and epigenetic mechanisms, and the interplay between SVAs and zinc fingers has been proposed as a major feature of genome evolution. We describe observations relating to the clustering patterns of both reference SVAs and polymorphic SVA insertions at zinc finger gene loci, suggesting that the evolution of this network may be ongoing in humans. Further, we propose a mechanism to direct future research and validation efforts, in which the interplay between zinc fingers and their epigenetic modulation of SVAs may regulate a network of zinc finger genes, with the potential for wider transcriptional consequences.

| S-EPMC6928650 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data