Ultra-Deep DNA Methylation Analysis of X-Linked Genes: GLA and AR as Model Genes
Open Access
- 4 June 2020
- Vol. 11 (6), 620
- https://doi.org/10.3390/genes11060620
Abstract
Recessive X-linked disorders may occasionally evolve in clinical manifestations of variable severity also in female carriers. For some of such diseases, the frequency of the symptoms’ appearance during women’s life may be particularly relevant. This phenomenon has been largely attributed to the potential skewness of the X-inactivation process leading to variable phenotypes. Nonetheless, in many cases, no correlation with X-inactivation unbalance was demonstrated. However, methods for analyzing skewness have been mainly limited to Human Androgen Receptor methylation analysis (HUMARA). Recently, the X-inactivation process has been largely revisited, highlighting the heterogeneity existing among loci in the epigenetic state within inactive and, possibly, active X-chromosomes. We reasoned that gene-specific and ultra-deep DNA methylation analyses could greatly help to unravel details of the X-inactivation process and the roles of specific X genes inactivation in disease manifestations. We recently provided evidence that studying DNA methylation at specific autosomic loci at a single-molecule resolution (epiallele distribution analysis) allows one to analyze cell-to-cell methylation differences in a given cell population. We here apply the epiallele analysis at two X-linked loci to investigate whether females show allele-specific epiallelic patterns. Due to the high potential of this approach, the method allows us to obtain clearly distinct allele-specific epiallele profiles.This publication has 23 references indexed in Scilit:
- X inactivation and reactivation in X-linked diseasesSeminars in Cell & Developmental Biology, 2016
- Characterization of CpG sites that escape methylation on the inactive human X-chromosomeEpigenetics, 2015
- X chromosome inactivation and active X upregulation in therian mammals: facts, questions, and hypothesesJournal of Molecular Cell Biology, 2015
- Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivationHuman Molecular Genetics, 2014
- Dynamic evolution of clonal epialleles revealed by methcloneGenome Biology, 2014
- Human active X-specific DNA methylation events showing stability across time and tissuesEuropean Journal of Human Genetics, 2014
- DNA methylation profiles of human active and inactive X chromosomesGenome Research, 2011
- Escape from X inactivation in mice and humansGenome Biology, 2010
- A skewed view of X chromosome inactivationJCI Insight, 2008
- The dynamics of X‐inactivation skewing as women ageClinical Genetics, 2004