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Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F17%3A10363549" target="_blank" >RIV/00064165:_____/17:10363549 - isvavai.cz</a>

  • Výsledek na webu

    <a href="http://dx.doi.org/10.1016/j.jaut.2017.05.005" target="_blank" >http://dx.doi.org/10.1016/j.jaut.2017.05.005</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.jaut.2017.05.005" target="_blank" >10.1016/j.jaut.2017.05.005</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins

  • Popis výsledku v původním jazyce

    Objective: To identify novel genetic and epigenetic factors associated with Myasthenia gravis (MG) using an identical twins experimental study design. Methods: The transcriptome and methylome of peripheral monocytes were compared between mono zygotic (MZ) twins discordant and concordant for MG, as well as with MG singletons and healthy controls, all females. Sets of differentially expressed genes and differentially methylated CpGs were validated using RT-PCR for expression and target bisulfite sequencing for methylation on additional samples. Results: &gt;100 differentially expressed genes and similar to 1800 differentially methylated CpGs were detected in peripheral monocytes between MG patients and controls. Several transcripts associated with immune homeostasis and inflammation resolution were reduced in MG patients. Only a relatively few genes differed between the discordant healthy and MG co-twins, and both their expression and methylation profiles demonstrated very high similarity. Interpretation: This is the first study to characterize the DNA methylation profile in MG, and the expression profile of immune cells in MZ twins with MG. Results suggest that numerous small changes in gene expression or methylation might together contribute to disease. Impaired monocyte function in MG and decreased expression of genes associated with inflammation resolution could contribute to the chronicity of the disease. Findings may serve as potential new predictive biomarkers for disease and disease activity, as well as potential future targets for therapy development. The high similarity between the healthy and the MG discordant twins, suggests that a molecular signature might precede a clinical phenotype, and that genetic predisposition may have a stronger contribution to. disease than previously assumed

  • Název v anglickém jazyce

    Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins

  • Popis výsledku anglicky

    Objective: To identify novel genetic and epigenetic factors associated with Myasthenia gravis (MG) using an identical twins experimental study design. Methods: The transcriptome and methylome of peripheral monocytes were compared between mono zygotic (MZ) twins discordant and concordant for MG, as well as with MG singletons and healthy controls, all females. Sets of differentially expressed genes and differentially methylated CpGs were validated using RT-PCR for expression and target bisulfite sequencing for methylation on additional samples. Results: &gt;100 differentially expressed genes and similar to 1800 differentially methylated CpGs were detected in peripheral monocytes between MG patients and controls. Several transcripts associated with immune homeostasis and inflammation resolution were reduced in MG patients. Only a relatively few genes differed between the discordant healthy and MG co-twins, and both their expression and methylation profiles demonstrated very high similarity. Interpretation: This is the first study to characterize the DNA methylation profile in MG, and the expression profile of immune cells in MZ twins with MG. Results suggest that numerous small changes in gene expression or methylation might together contribute to disease. Impaired monocyte function in MG and decreased expression of genes associated with inflammation resolution could contribute to the chronicity of the disease. Findings may serve as potential new predictive biomarkers for disease and disease activity, as well as potential future targets for therapy development. The high similarity between the healthy and the MG discordant twins, suggests that a molecular signature might precede a clinical phenotype, and that genetic predisposition may have a stronger contribution to. disease than previously assumed

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30103 - Neurosciences (including psychophysiology)

Návaznosti výsledku

  • Projekt

  • Návaznosti

    V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Ostatní

  • Rok uplatnění

    2017

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název periodika

    Journal of Autoimmunity

  • ISSN

    0896-8411

  • e-ISSN

  • Svazek periodika

    82

  • Číslo periodika v rámci svazku

    August

  • Stát vydavatele periodika

    GB - Spojené království Velké Británie a Severního Irska

  • Počet stran výsledku

    12

  • Strana od-do

    62-73

  • Kód UT WoS článku

    000407537500006

  • EID výsledku v databázi Scopus

    2-s2.0-85019638521