Identification of a DNA methylation signature in blood cells from persons with down syndrome

Maria Giulia Bacalini, Davide Gentilini, Alessio Boattini, Enrico Giampieri, Chiara Pirazzini, Cristina Giuliani, Elisa Fontanesi, Maria Scurti, Daniel Remondini, Miriam Capri, Guido Cocchi, Alessandro Ghezzo, Alberto Del Rio, Donata Luiselli, Giovanni Vitale, Daniela Mari, Gastone Castellani, Mario Fraga, Anna Maria Di Blasio, Stefano SalvioliClaudio Franceschi, Paolo Garagnani

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)82-96
Number of pages15
Issue number2
Publication statusPublished - 2015


  • Aging
  • DNA methylation
  • Down syndrome
  • Epigenetics
  • Infinium human methylation 450 beadchip

ASJC Scopus subject areas

  • Ageing
  • Cell Biology


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