title: Identification of a DNA methylation signature in blood cells from persons with Down Syndrome.
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.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.|Personal Genomics S.r.l., Verona 37134, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Bacalini
authors.affiliation: Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Cusano Milanino, Milan 20095, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gentilini
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna 40126, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Boattini
authors.affiliation: Department of Physics and Astronomy, University of Bologna, Bologna 40126, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Giampieri
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pirazzini
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna 40126, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Giuliani
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fontanesi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Scurti
authors.affiliation: Department of Physics and Astronomy, University of Bologna, Bologna 40126, Italy.
authors.forename: Daniel
authors.initials: D
authors.lastname: Remondini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.affiliation: Department of Medical and Surgical Sciences-Neonatology and Neonatal Intensive Care Unit, University of Bologna, Bologna 40126, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Cocchi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ghezzo
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Institute of Organic Synthesis and Photoreactivity (ISOF) National Research Council (CNR), Bologna 40126, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Rio
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna 40126, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Luiselli
authors.affiliation: Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Cusano Milanino, Milan 20095, Italy.|Department of Clinical Sciences and Community Health, University of Milan, Milan 20095, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan 20095, Italy.|Geriatric Unit, IRCCS Ca' Granda Foundation Maggiore Policlinico Hospital, Milan 20095, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mari
authors.affiliation: Department of Physics and Astronomy, University of Bologna, Bologna 40126, Italy.
authors.forename: Gastone
authors.initials: G
authors.lastname: Castellani
authors.affiliation: Cancer Epigenetics Laboratory, Instituto Universitario de de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain.|Department of Immunology & Oncology, Centro Nacional de Biotecnología/CNB-CSIC, Cantoblanco, Madrid, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Fraga
authors.affiliation: Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Cusano Milanino, Milan 20095, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Blasio
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Salvioli
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.|IRCCS Institute of Neurological Sciences, Bologna 40126, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.|Personal Genomics S.r.l., Verona 37134, Italy.|Applied Biomedical Research Center, S. Orsola-Malpighi Polyclinic, Bologna 40138, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Garagnani
mesh_terms: D019175:DNA Methylation; D004314:Down Syndrome / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D063990:Gene Ontology; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism*; D008297:Male