Journal ArticleScience · July 5, 2024
Transcribed enhancer maps can reveal nuclear interactions underpinning each cell type and connect specific cell types to diseases. Using a 5' single-cell RNA sequencing approach, we defined transcription start sites of enhancer RNAs and other classes of co ...
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Journal ArticleSci Rep · June 25, 2024
A previous study suggested that fetal inheritance of chromosomally integrated human herpesvirus 6 (ici-HHV6) is associated with the hypertensive pregnancy disorder preeclampsia (PE). We aimed to study this question utilizing cord plasma samples (n = 1276) ...
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Journal ArticleHum Mol Genet · June 5, 2023
Von Hippel-Lindau (VHL) disease is an autosomal dominant, inherited syndrome with variants in the VHL gene, causing predisposition to multi-organ neoplasms with vessel abnormality. Germline variants in VHL can be detected in 80-90% of patients clinically d ...
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Journal ArticleNat Genet · June 2023
Mobile genetic elements (MEs) are heritable mutagens that recursively generate structural variants (SVs). ME variants (MEVs) are difficult to genotype and integrate in statistical genetics, obscuring their impact on genome diversification and traits. We de ...
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Journal ArticleCurr Opin Genet Dev · June 2023
Transposable elements (TEs) such as endogenous retroviruses (ERVs), long interspersed nuclear elements (LINEs), and short interspersed nuclear elements (SINEs) occupy nearly half of typical mammalian genomes. Previous studies show that these parasitic elem ...
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Journal ArticleNat Biomed Eng · June 2023
Gene transcription is regulated through complex mechanisms involving non-coding RNAs (ncRNAs). As the transcription of ncRNAs, especially of enhancer RNAs, is often low and cell type specific, how the levels of RNA transcription depend on genotype remains ...
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Journal ArticleBiochem Biophys Res Commun · May 28, 2023
Viral infection induces diverse cellular immune responses. Some viruses induce the production of antiviral cytokines, alterations of endogenous gene expression, and apoptosis; however, other viruses replicate without inducing such responses, enabling them ...
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Journal ArticlePLoS Genet · May 2022
Mammalian germ cells stem from primordial germ cells (PGCs). Although the gene regulatory network controlling the development of germ cells such as PGCs is critical for ensuring gamete integrity, substantial differences exist in this network among mammalia ...
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Journal ArticlePLoS Pathog · December 2021
There are strong incentives for human populations to develop antiviral systems. Similarly, genomes that encode antiviral systems have had strong selective advantages. Protein-guided immune systems, which have been well studied in mammals, are necessary for ...
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Journal ArticlePLoS Comput Biol · October 2021
Viruses are the most numerous biological entity, existing in all environments and infecting all cellular organisms. Compared with cellular life, the evolution and origin of viruses are poorly understood; viruses are enormously diverse, and most lack sequen ...
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Journal ArticlePLoS Genet · April 2021
Acquisition of genetic material from viruses by their hosts can generate inter-host structural genome variation. We developed computational tools enabling us to study virus-derived structural variants (SVs) in population-scale whole genome sequencing (WGS) ...
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Journal ArticleProc Natl Acad Sci U S A · February 2, 2021
Understanding the genetics and taxonomy of ancient viruses will give us great insights into not only the origin and evolution of viruses but also how viral infections played roles in our evolution. Endogenous viruses are remnants of ancient viral infection ...
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Journal ArticleMol Biol Evol · January 4, 2021
Human herpesvirus 6A and 6B (HHV-6) can integrate into the germline, and as a result, ∼70 million people harbor the genome of one of these viruses in every cell of their body. Until now, it has been largely unknown if 1) these integrations are ancient, 2) ...
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Journal ArticleJCO Precis Oncol · November 2020
PUPOSE: We investigated the prevalence and spectrum of pathogenic germline variants in patients with early-onset colorectal cancer (CRC), breast cancer (BC), and prostate cancer (PCA) in the Japanese population. We also identified pathogenic variants in ot ...
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Journal ArticleNat Struct Mol Biol · October 2020
Gene regulation in the germline ensures the production of high-quality gametes, long-term maintenance of the species and speciation. Male germline transcriptomes undergo dynamic changes after the mitosis-to-meiosis transition and have been subject to evolu ...
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Journal ArticlePLoS Genet · August 2020
Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactivate into an infectious virus. HHV-6 integr ...
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Journal ArticleTrends Immunol · November 2019
Eukaryotic genomes contain virus-derived sequences called endogenous virus elements (EVEs). The majority of EVEs are related to retroviruses, which integrate into the host genome in order to replicate. Some retroviral EVEs encode a function; for example, s ...
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Journal ArticleTransplant Direct · March 2019
BACKGROUND: Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States, although nonalcoholic steatohepatitis (NASH) is on the rise. Increasingly effective HCV antivirals are available, but their association ...
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Journal ArticleNat Commun · April 10, 2018
HIV-1 causes chronic inflammation and AIDS in humans, whereas related simian immunodeficiency viruses (SIVs) replicate efficiently in their natural hosts without causing disease. It is currently unknown to what extent virus-specific properties are responsi ...
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Journal ArticleCell · January 11, 2018
Arc, a master regulator of synaptic plasticity, contains sequence elements that are evolutionarily related to retrotransposon Gag genes. Two related papers in this issue of Cell show that Arc retains retroviral-like capsid-forming ability and can transmit ...
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Journal ArticleCurr Opin Microbiol · June 2016
Reverse-transcribed RNA molecules compose a significant portion of the human genome. Many of these RNA molecules were retrovirus genomes either infecting germline cells or having done so in a previous generation but retaining transcriptional activity. This ...
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Journal ArticleNature · October 1, 2015
The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having recons ...
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Journal ArticleNature · October 1, 2015
Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we c ...
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Journal ArticleRNA · October 2015
Endogenous bornavirus-like nucleoprotein elements (EBLNs) are sequences within vertebrate genomes derived from reverse transcription and integration of ancient bornaviral nucleoprotein mRNA via the host retrotransposon machinery. While species with EBLNs a ...
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Journal ArticleCell Rep · September 8, 2015
Endogenous bornavirus-like nucleoprotein elements (EBLNs) are DNA sequences in vertebrate genomes formed by the retrotransposon-mediated integration of ancient bornavirus sequence. Thus, EBLNs evidence a mechanism of retrotransposon-mediated RNA-to-DNA inf ...
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Journal ArticleNat Commun · June 1, 2015
Investigating genomic structural variants at basepair resolution is crucial for understanding their formation mechanisms. We identify and analyse 8,943 deletion breakpoints in 1,092 samples from the 1000 Genomes Project. We find breakpoints have more nearb ...
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Journal ArticlemBio · April 21, 2015
UNLABELLED: Broadly cross-reactive neutralizing antibodies (bNabs) represent powerful tools to combat human immunodeficiency virus type 1 (HIV-1) infection. Here, we examined whether HIV-1-specific bNabs are capable of cross-neutralizing distantly related ...
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Journal ArticleSci Rep · March 3, 2015
Borna disease virus (BDV) has a non-segmented, negative-stranded RNA genome and causes persistent infection in many animal species. Previous study has shown that the activation of the IκB kinase (IKK)/NF-κB pathway is reduced by BDV infection even in cells ...
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Journal ArticleCell Host Microbe · May 15, 2013
Receptor engagement by HIV-1 during host cell entry activates signaling pathways that can reprogram the cell for optimal viral replication. To obtain a global view of the signaling events induced during HIV-1 entry, we conducted a quantitative phosphoprote ...
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Journal ArticleProc Natl Acad Sci U S A · April 23, 2013
Defining the virus-host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify ...
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Journal ArticleJ Virol · March 2013
Infection by HIV-1 most often results from the successful transmission and propagation of a single virus variant, termed the transmitted/founder (T/F) virus. Here, we compared the attachment and entry properties of envelope (Env) glycoproteins from T/F and ...
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Journal ArticleVirology · February 5, 2013
We report the molecular identification, cloning and initial biological characterization of 12 full-length HIV-1 subtype A, D and A/D recombinant transmitted/founder (T/F) genomes. T/F genomes contained intact canonical open reading frames and all T/F virus ...
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Journal ArticleJ Virol · April 2012
African green monkeys (AGMs) are naturally infected with a simian immunodeficiency virus (SIVagm) that is nonpathogenic in its host. Although SIVagm is common and widespread, little is known about the mechanisms that govern its transmission. Since the earl ...
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Journal ArticlePLoS Pathog · 2012
Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottle ...
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Journal ArticleJ Virol · October 2011
The great majority of human immunodeficiency virus type 1 (HIV-1) strains enter CD4+ target cells by interacting with one of two coreceptors, CCR5 or CXCR4. Here we describe a transmitted/founder (T/F) virus (ZP6248) that was profoundly impaired in its abi ...
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Journal ArticleJ Virol · September 2011
Sexual transmission of human immunodeficiency virus type 1 (HIV-1) across mucosal barriers is responsible for the vast majority of new infections. This relatively inefficient process results in the transmission of a single transmitted/founder (T/F) virus, ...
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Journal ArticleJ Virol · December 2010
Understanding the lack of disease progression in nonpathogenic simian immunodeficiency virus (SIV) infections is essential for deciphering the immunopathogenesis of human AIDS. Yet, in vivo studies have been hampered by a paucity of infectious molecular cl ...
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Journal ArticleVirology · February 20, 2010
Functional studies of HIV-1 envelope glycoproteins (Envs) commonly include the generation of pseudoviruses, which are produced by co-transfection of rev-vpu-env cassettes with an env-deficient provirus. Here, we describe six Env constructs from transmitted ...
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Journal ArticleJ Exp Med · June 8, 2009
Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 ac ...
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Journal ArticleJ Antimicrob Chemother · April 2009
OBJECTIVES: To determine the functional relationship between the density of bacteria and the pharmacodynamics of antibiotics, and the potential consequences of this inoculum effect on the microbiological course of antibiotic treatment of Staphylococcus aur ...
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