TY - JOUR
T1 - Identification of a DNA methylation signature in blood cells from persons with down syndrome
AU - Bacalini, Maria Giulia
AU - Gentilini, Davide
AU - Boattini, Alessio
AU - Giampieri, Enrico
AU - Pirazzini, Chiara
AU - Giuliani, Cristina
AU - Fontanesi, Elisa
AU - Scurti, Maria
AU - Remondini, Daniel
AU - Capri, Miriam
AU - Cocchi, Guido
AU - Ghezzo, Alessandro
AU - Rio, Alberto Del
AU - Luiselli, Donata
AU - Vitale, Giovanni
AU - Mari, Daniela
AU - Castellani, Gastone
AU - Fraga, Mario
AU - Di Blasio, Anna Maria
AU - Salvioli, Stefano
AU - Franceschi, Claudio
AU - Garagnani, Paolo
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Aging
KW - DNA methylation
KW - Down syndrome
KW - Epigenetics
KW - Infinium human methylation 450 beadchip
UR - http://www.scopus.com/inward/record.url?scp=84924940199&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924940199&partnerID=8YFLogxK
M3 - Article
C2 - 25701644
AN - SCOPUS:84924940199
VL - 7
SP - 82
EP - 96
JO - Aging
JF - Aging
SN - 1945-4589
IS - 2
ER -