Abstract
BackgroundAbnormal 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.ResultsDNA 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.ConclusionsThe presented data clearly show that gain or loss of an X chromosome results in different epigenetic effects, which are not necessary opposite.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0112-2) contains supplementary material, which is available to authorized users.
Highlights
Abnormal sex chromosome numbers in humans are observed in Turner (45,X) and Klinefelter (47,XXY) syndromes
On the X chromosome, a large number of differences were observed when a sample with one X was compared to another sample of two X, as in the comparison of Turner samples to female samples and male samples to Klinefelter samples
This in turn suggests that the X chromosome in Turner individuals is as active as it is in males and that the second X in Klinefelter individuals is as inactivated as it is in females
Summary
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. Sharma et al Clinical Epigenetics (2015) 7:76 most common in men (1/500) and Turner syndrome (45,X) most common in women (1/2500) [5] Such chromosomal abnormalities lead to a high risk of miscarriage and stillbirth. Klinefelter syndrome, on the other hand, apart from phenotypic features, such as high stature, gynecomastia, and infertility, is often linked to declined verbal skills [7] Both syndromes have the hallmark characteristic of abnormal endocrine balance and display hypergonadotropic hypogonadism [8,9,10]. Molecular insights on epigenetic changes responsible for the occurrence of these phenotypes are missing
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
