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    In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes

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    Faisal_Functional_and_Integrative_Genomics.pdf (570.0Kb)
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    Publication date
    2016-05
    Author
    Taqi, M.M.
    Waseem, D.
    Ismatullah, H.
    Haider, S.A.
    Faisal, Muhammad
    Keyword
    Phospholipase C epsilon (PLCE1); MICB; Transcription factors; Dengue-associated SNPs; Mutated PLCε protein
    Rights
    © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. This article is published with open access at Springerlink.com
    Peer-Reviewed
    Yes
    
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    Abstract
    Single nucleotide polymorphisms (SNPs) in PLCE1 and MICB genes increase risk for the development of dengue shock syndrome (DSS). We used Bioinformatics tools to predict alterations at the transcriptional and posttranslational levels driven by PLCE1 and MICB SNPs associated with DSS. Functional and phenotypic analysis conducted to determine deleterious SNPs and impact of amino acid substitution on the structure and function of proteins identified rs2274223 (H1619R) as deleterious to protein coding as it induces structural change in the C2 domain of PLCε, with the mutant residue more positively charged than the wild-type residue (RMSD score, 1.75 Å).Moreover, rs2274223 condenses the chromatinrepressing PLCε expression in DSS. Briefly, this study presents the impact of a single nucleotide transition at SNPs associated with DSS on differential protein binding patterns with PLCE1 and MICB genes and on protein structure modification and their possible role in the pathogenesis of DSS.
    URI
    http://hdl.handle.net/10454/8492
    Version
    published version paper
    Citation
    Taqi MM, Waseem D, Ismatullah H, Haider SA and Faisal M (2016) In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes. Functional & Integrative Genomics. 16(3): 335-345.
    Link to publisher’s version
    http://dx.doi.org/10.1007/s10142-016-0489-9
    Type
    Article
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    Health Studies Publications

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