Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome
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 report...
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Public Library of Science
2011
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| Online Access: | https://eprints.nottingham.ac.uk/2603/ |
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| author | Stöger, Reinhard Genereux, Diane P. Hagerman, Randi J. Hagerman, Paul J. Tassone, Flora Laird, Charles D. |
| author_facet | Stöger, Reinhard Genereux, Diane P. Hagerman, Randi J. Hagerman, Paul J. Tassone, Flora Laird, Charles D. |
| author_sort | Stöger, Reinhard |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T18:18:48Z |
| format | Article |
| id | nottingham-2603 |
| institution | University of Nottingham Malaysia Campus |
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| last_indexed | 2025-11-14T18:18:48Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-26032020-05-04T16:30:57Z https://eprints.nottingham.ac.uk/2603/ 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. 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. Public Library of Science 2011-08-31 Article PeerReviewed Stöger, Reinhard, Genereux, Diane P., Hagerman, Randi J., Hagerman, Paul J., Tassone, Flora and Laird, Charles 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). e23648/1- e23648/9. ISSN 1932-6203 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0023648 doi:10.1371/journal.pone.0023648 doi:10.1371/journal.pone.0023648 |
| spellingShingle | Stöger, Reinhard Genereux, Diane P. Hagerman, Randi J. Hagerman, Paul J. Tassone, Flora Laird, Charles D. Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome |
| title | Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome |
| title_full | Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome |
| title_fullStr | Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome |
| title_full_unstemmed | Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome |
| title_short | Testing the FMR1 promoter for mosaicism in DNA methylation among CpG sites, strands, and cells in FMR1-expressing males with fragile X syndrome |
| title_sort | testing the fmr1 promoter for mosaicism in dna methylation among cpg sites, strands, and cells in fmr1-expressing males with fragile x syndrome |
| url | https://eprints.nottingham.ac.uk/2603/ https://eprints.nottingham.ac.uk/2603/ https://eprints.nottingham.ac.uk/2603/ |