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Research Paper|Volume 7, Issue 2|pp 82—96

Identification of a DNA methylation signature in blood cells from persons with Down Syndrome

Maria Giulia Bacalini1,2,3, Davide Gentilini4, Alessio Boattini5, Enrico Giampieri6, Chiara Pirazzini1,2, Cristina Giuliani5, Elisa Fontanesi1,2, Maria Scurti1,2, Daniel Remondini6, Miriam Capri1,2, Guido Cocchi7, Alessandro Ghezzo1, Alberto Del Rio1,8, Donata Luiselli5, Giovanni Vitale4,9, Daniela Mari9,10, Gastone Castellani6, Mario Fraga11,12, Anna Maria Di Blasio4, Stefano Salvioli1,2, Claudio Franceschi1,2,13, Paolo Garagnani1,2,3,14
  • 1Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum - University of Bologna, Bologna 40138, Italy
  • 2Interdepartmental Center “L. Galvani”, University of Bologna, Bologna 40126, Italy
  • 3Personal Genomics S.r.l., Verona 37134, Italy
  • 4Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Via Zucchi 18, Cusano Milanino, 20095 Milan, Italy
  • 5Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna 40126, Italy
  • 6Department of Physics and Astronomy, University of Bologna, Bologna 40126, Italy
  • 7Department of Medical and Surgical Sciences - Neonatology and Neonatal Intensive Care Unit, University of Bologna, Italy
  • 8Institute of Organic Synthesis and Photoreactivity (ISOF) National Research Council (CNR), Bologna 40126, Italy
  • 9Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
  • 10Geriatric Unit, IRCCS Ca' Granda Foundation Maggiore Policlinico Hospital, Milan, Italy
  • 11Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain
  • 12Department of Immunology & Oncology, Centro Nacional de Biotecnología/CNB-CSIC, Cantoblanco, Madrid, Spain
  • 13IRCCS Institute of Neurological Sciences, Bologna, Italy
  • 14Applied Biomedical Research Center, S. Orsola-Malpighi Polyclinic, Bologna 40138, Italy
Received: December 24, 2014Accepted: January 5, 2014Published: January 8, 2014
https://doi.org/10.18632/aging.100715

Copyright: © 2014 Bacalini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Down Syndrome (DS) is characterized by a wide spectrum of clinical signs, which include segmental premature aging of central nervous and immune systems. Although it is well established that the causative defect of DS is the trisomy of chromosome 21, the molecular bases of its phenotype are still largely unknown. We used the Infinium HumanMethylation450 BeadChip to investigate DNA methylation patterns in whole blood from 29 DS persons, using their relatives (mothers and unaffected siblings) as controls. This family-based model allowed us to monitor possible confounding effects on DNA methylation patterns deriving from genetic and environmental factors. Although differentially methylated regions (DMRs) displayed a genome-wide distribution, they were enriched on chromosome 21. DMRs mapped in genes involved in developmental functions, including embryonic development (HOXA family) and haematological (RUNX1 and EBF4) and neuronal (NCAM1) development. Moreover, genes involved in the regulation of chromatin structure (PRMD8, KDM2B, TET1) showed altered methylation. The data also showed that several pathways are affected in DS, including PI3K-Akt signaling. In conclusion, we identified an epigenetic signature of DS that sustains a link between developmental defects and disease phenotype, including segmental premature aging.