Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Changes in the Pattern of DNA Methylation Associate with Twin Discordance in SLE

ABSTRACT: This is the first high-throughput analysis of DNA methylation in autoimmune diseases. We have used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease. Total DNA isolated by standard procedures from 59 White Blood Cell (WBC) samples corresponding to monozygotic twins discordant for three different autoimmune diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and dermatomyositis (DM) and two additional controls for each MZ twin pair.

ORGANISM(S): Homo sapiens

SUBMITTER: Reiner Siebert

PROVIDER: E-GEOD-19033 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus.

Javierre Biola M BM Fernandez Agustin F AF Richter Julia J Al-Shahrour Fatima F Martin-Subero J Ignacio JI Rodriguez-Ubreva Javier J Berdasco Maria M Fraga Mario F MF O'Hanlon Terrance P TP Rider Lisa G LG Jacinto Filipe V FV Lopez-Longo F Javier FJ Dopazo Joaquin J Forn Marta M Peinado Miguel A MA Carreño Luis L Sawalha Amr H AH Harley John B JB Siebert Reiner R Esteller Manel M Miller Frederick W FW Ballestar Esteban E

Genome research 20091222 2

Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a ...[more]

PMID: 20028698

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Project description:DNA methylation appears to play an essential mechanistic role in the pathogenesis of ALL, thereby potentiate its use as a biomarker for diagnosis and prognosis (Milani, Lundmark et al. 2010; Geng, Brennan et al. 2012; Sandoval, Heyn et al. 2013), and even a potential target of novel therapeutic approaches in ALL. In present study, we collected blood specimens for 4 pairs of monozygotic twins (MZ) and 1 pair of dizygotic twin (DZ) that are discordant for ALL. We sought to comprehensively assess the magnitude of genetic and epigenetic differences between ALL-affected and unaffected twins. we conducted whole genome and whole methylome sequencing on these five pairs of ALL-discordant twins. We also examined both the MZ and DZ twins using whole-genome bisulfite sequencing (WGBS). At first, the methylation differences across the genome were addressed globally by Circos software. And then tried to characterize the co-twin methylation divergence in specific genomic regions between ALL-discordant twin pairs. These patterns of dynamic co-twin methylation changes in these discordant ALL samples were generally consistent among MZ and DZ twins, indicating similarities of methylation abnormalities. As a result, 780, 566, 309, 293 and 2110 DMRs were identified, with a similar distribution pattern across different genomic elements among the five twin pairs.Then we annotate whether these DMRs were located in regulatory elements and identification of genes with recurring methylation alterations in a cohort of ALL patients. We collected blood specimens from 4 pairs of MZ twins and 1 pair of DZ twin that are discordant for ALL. At first, the methylation differences across the genome were addressed globally by Circos software. And then tried to characterize the co-twin methylation divergence in specific genomic regions and differentially methylated gene regions (DMRs) were identified between ALL-discordant twin pairs. Then we annotate whether these DMRs were located in regulatory elements and identification of genes with recurring methylation alterations in a cohort of ALL patients.

Dataset Information

Changes in the Pattern of DNA Methylation Associate with Twin Discordance in SLE

Publications

Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus.

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