title: DNA methylation signature in peripheral blood reveals distinct characteristics of human X chromosome numerical aberrations.
abstract: BACKGROUND
  Abnormal sex chromosome numbers in humans are observed in Turner (45,X) and Klinefelter (47,XXY) syndromes. Both syndromes are associated with several clinical phenotypes, whose molecular mechanisms are obscure, and show a range of inter-individual penetrance. In order to understand the effect of abnormal numbers of X chromosome on the methylome and its correlation to the variable clinical phenotype, we performed a genome-wide methylation analysis using MeDIP and Illumina's Infinium assay on individuals with four karyotypes: 45,X, 46,XY, 46,XX, and 47,XXY.
  
  
  RESULTS
  DNA methylation changes were widespread on all autosomal chromosomes in 45,X and in 47,XXY individuals, with Turner individuals presenting five times more affected loci. Differentially methylated CpGs, in most cases, have intermediate methylation levels and tend to occur outside CpG islands, especially in individuals with Turner syndrome. The X inactivation process appears to be less effective in Klinefelter syndrome as methylation on the X was decreased compared to normal female samples. In a large number of individuals, we verified several loci by pyrosequencing and observed only weak inter-loci correlations between the verified regions. This suggests a certain stochastic/random contribution to the methylation changes at each locus. Interestingly, methylation patterns on some PAR2 loci differ between male and Turner syndrome individuals and between female and Klinefelter syndrome individuals, which possibly contributed to this distinguished and unique autosomal methylation patterns in Turner and Klinefelter syndrome individuals.
  
  
  CONCLUSIONS
  The presented data clearly show that gain or loss of an X chromosome results in different epigenetic effects, which are not necessary opposite.
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
authors.forename: Muhammad Ahmer
authors.initials: MA
authors.lastname: Jamil
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Nuesgen
authors.affiliation: Pediatric Endocrinology Division, Children's Hospital, University of Bonn, Bonn, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Schreiner
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Priebe
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Per
authors.initials: P
authors.lastname: Hoffmann
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Herns
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Institute for Computer Science, c/o Bonn-Aachen International Center for IT, Algorithmic Bioinformatics, University of Bonn, Dahlmannstr. 2, 53113 Bonn, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Fröhlich
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Pediatric Endocrinology Division, Children's Hospital, University of Bonn, Bonn, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Woelfle
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
authors.forename: Osman
authors.initials: O
authors.lastname: El-Maarri
keywords: DNA methylation; Epigenetics; Klinefelter; PAR region; Turner; X chromosome inactivation