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: >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: >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