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Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome

Stöger, Reinhard; Genereux, Diane P.; Hagerman, Randi J.; Hagerman, Paul J.; Tassone, Flora; Laird, Charles D.

Authors

Reinhard Stöger

Diane P. Genereux

Randi J. Hagerman

Paul J. Hagerman

Flora Tassone

Charles D. Laird

Abstract

Variability among individuals in the severity of fragile X syndrome (FXS) is influenced by epigenetic methylation mosaicism, which may also be common in other complex disorders. The epigenetic signal of dense promoter DNA methylation is usually associated with gene silencing, as was initially reported for FMR1 alleles in individuals with FXS. A paradox arose when significant levels of FMR1 mRNA were reported for some males with FXS who had been reported to have predominately methylated alleles. We have used hairpin-bisufite PCR, validated with molecular batch-stamps and barcodes, to collect and assess double-stranded DNA methylation patterns from these previously studied males. These patterns enable us to distinguish among three possible forms of methylation mosaicism, any one of which could explain FMR1 expression in these males. Our data indicate that cryptic inter-cell mosaicism in DNA methylation can account for the presence of FMR1 mRNA in some individuals with FXS.

Journal Article Type Article
Publication Date Aug 31, 2011
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 6
Issue 8
Article Number e23648
Institution Citation Stöger, R., Genereux, D. P., Hagerman, R. J., Hagerman, P. J., Tassone, F., & Laird, C. D. (2011). Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome. PLoS ONE, 6(8), doi:10.1371/journal.pone.0023648
DOI https://doi.org/10.1371/journal.pone.0023648
Publisher URL http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0023648
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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