Genome-wide analysis of DNA methylation, copy number variation, and gene expression in monozygotic twins discordant for primary biliary cirrhosis

Carlo Selmi, Francesca Cavaciocchi, Ana Lleo, Cristina Cheroni, Raffaele De Francesco, Simone A. Lombardi, Maria De Santis, Francesca Meda, Maria Gabriella Raimondo, Chiara Crotti, Marco Folci, Luca Zammataro, Marlyn J. Mayo, Nancy Bach, Shinji Shimoda, Stuart C. Gordon, Monica Miozzo, Pietro Invernizzi, Mauro Podda, Rossana ScavelliMichelle R. Martin, Janine M LaSalle, M. Eric Gershwin

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Primary biliary cirrhosis (PBC) is an uncommon autoimmune disease with a homogeneous clinical phenotype that reflects incomplete disease concordance in monozygotic (MZ) twins. We have taken advantage of a unique collection consisting of genomic DNA and mRNA from peripheral blood cells of female MZ twins (n = 3 sets) and sisters of similar age (n = 8 pairs) discordant for disease. We performed a genome-wide study to investigate differences in (i) DNA methylation (using a custom tiled four-plex array containing tiled 50-mers 19,084 randomly chosen methylation sites), (ii) copy number variation (CNV) (with a chip including markers derived from the 1000 Genomes Project, all three HapMap phases, and recently published studies), and/or (iii) gene expression (by whole-genome expression arrays). Based on the results obtained from these three approaches we utilized quantitative PCR to compare the expression of candidate genes. Importantly, our data support consistent differences in discordant twins and siblings for the (i) methylation profiles of 60 gene regions, (ii) CNV of 10 genes, and (iii) the expression of 2 interferon-dependent genes. Quantitative PCR analysis showed that 17 of these genes are differentially expressed in discordant sibling pairs. In conclusion, we report that MZ twins and sisters discordant for PBC manifest particular epigenetic differences and highlight the value of the epigenetic study of twins.

Original languageEnglish (US)
Article numberArticle 128
JournalFrontiers in Immunology
Volume5
Issue numberMAR
DOIs
StatePublished - 2014

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Keywords

  • Autoimmune cholangitis
  • Environment
  • Epigenetics

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Selmi, C., Cavaciocchi, F., Lleo, A., Cheroni, C., De Francesco, R., Lombardi, S. A., De Santis, M., Meda, F., Raimondo, M. G., Crotti, C., Folci, M., Zammataro, L., Mayo, M. J., Bach, N., Shimoda, S., Gordon, S. C., Miozzo, M., Invernizzi, P., Podda, M., ... Gershwin, M. E. (2014). Genome-wide analysis of DNA methylation, copy number variation, and gene expression in monozygotic twins discordant for primary biliary cirrhosis. Frontiers in Immunology, 5(MAR), [Article 128]. https://doi.org/10.3389/fimmu.2014.00128