41 research outputs found

    A Genome-Wide Comparative Evolutionary Analysis of Herpes Simplex Virus Type 1 and Varicella Zoster Virus

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    Herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are closely related viruses causing lifelong infections. They are typically associated with mucocutaneous or skin lesions, but may also cause severe neurological or ophthalmic diseases, possibly due to viral- and/or host-genetic factors. Although these viruses are well characterized, genome-wide evolutionary studies have hitherto only been presented for VZV. Here, we present a genome-wide study on HSV-1. We also compared the evolutionary characteristics of HSV-1 with those for VZV. We demonstrate that, in contrast to VZV for which only a few ancient recombination events have been suggested, all HSV-1 genomes contain mosaic patterns of segments with different evolutionary origins. Thus, recombination seems to occur extremely frequent for HSV-1. We conclude by proposing a timescale for HSV-1 evolution, and by discussing putative underlying mechanisms for why these otherwise biologically similar viruses have such striking evolutionary differences

    Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

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    Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

    Milk: an epigenetic amplifier of FTO-mediated transcription? Implications for Western diseases

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    VZV phylogeny.

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    <p>Phylogenetic network (splits network) of available complete genome VZV sequences. The strains are divided into clades 1 to 5, and the deep lineage reticulate topology is caused by a few ancient recombination events described previously. The network also presents a reticulate pattern within clade 1 caused by a putative recent recombination event involving strain SVETA.</p

    HSV-1 timescale estimation based on the genes US7 and US8.

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    <p>Estimated timescale for the HSV-1 evolution. Each major branch point in the phylogenetic tree is marked with a dotted line to the scale-bar below. The 95% confidence intervals for each predicted time since divergence are denoted with purple bars. The increased number of branch points in each clade is highlighted with green background. Posterior probabilities for the major clades are shown.</p

    HSV-1 recombination analysis.

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    <p>Recombination analysis using Bootscan and SimPlot. A and B illustrate the bootscan and SimPlot analysis of query sequences 2762 and 4-J1037, respectively, which were classified as non-recombinants based on the US7–US8 regions. Bootscan plots demonstrate highly fragmented genomes as a result of recombination. Similarity plots demonstrate the sequence similarity between the query sequence and the other sequences. C and D depicts the bootscan analysis of the reference strains F and 17. Nucleotide positions refer to the sequence alignment excluding gaps and repeat regions.</p
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