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Aging (Albany NY). 2015 Feb;7(2):82-96.

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

Author information

1
Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.
2
Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.
3
Personal Genomics S.r.l., Verona 37134, Italy.
4
Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Cusano Milanino, Milan 20095, Italy.
5
Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna 40126, Italy.
6
Department of Physics and Astronomy, University of Bologna, Bologna 40126, Italy.
7
Department of Medical and Surgical Sciences-Neonatology and Neonatal Intensive Care Unit, University of Bologna, Bologna 40126, Italy.
8
Institute of Organic Synthesis and Photoreactivity (ISOF) National Research Council (CNR), Bologna 40126, Italy.
9
Department of Clinical Sciences and Community Health, University of Milan, Milan 20095, Italy.
10
Geriatric Unit, IRCCS Ca' Granda Foundation Maggiore Policlinico Hospital, Milan 20095, Italy.
11
Cancer Epigenetics Laboratory, Instituto Universitario de de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain.
12
Department of Immunology & Oncology, Centro Nacional de Biotecnología/CNB-CSIC, Cantoblanco, Madrid, Spain.
13
IRCCS Institute of Neurological Sciences, Bologna 40126, Italy.
14
Applied Biomedical Research Center, S. Orsola-Malpighi Polyclinic, Bologna 40138, Italy.

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.

PMID:
25701644
PMCID:
PMC4359691
DOI:
10.18632/aging.100715
[Indexed for MEDLINE]
Free PMC Article

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