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Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus

BACKGROUND: Fragile X syndrome (FXS) is a common form of inherited intellectual disability caused by an expansion of CGG repeats located in the 5(′) untranslated region (UTR) of the FMR1 gene, which leads to hypermethylation and silencing of this locus. Although a dramatic increase in DNA methylatio...

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Autores principales: Alisch, Reid S, Wang, Tao, Chopra, Pankaj, Visootsak, Jeannie, Conneely, Karen N, Warren, Stephen T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599197/
https://www.ncbi.nlm.nih.gov/pubmed/23356558
http://dx.doi.org/10.1186/1471-2350-14-18
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author Alisch, Reid S
Wang, Tao
Chopra, Pankaj
Visootsak, Jeannie
Conneely, Karen N
Warren, Stephen T
author_facet Alisch, Reid S
Wang, Tao
Chopra, Pankaj
Visootsak, Jeannie
Conneely, Karen N
Warren, Stephen T
author_sort Alisch, Reid S
collection PubMed
description BACKGROUND: Fragile X syndrome (FXS) is a common form of inherited intellectual disability caused by an expansion of CGG repeats located in the 5(′) untranslated region (UTR) of the FMR1 gene, which leads to hypermethylation and silencing of this locus. Although a dramatic increase in DNA methylation of the FMR1 full mutation allele is well documented, the extent to which these changes affect DNA methylation throughout the rest of the genome has gone unexplored. METHODS: Here we examined genome-wide methylation in both peripheral blood (N = 62) and induced pluripotent stem cells (iPSCs; N = 10) from FXS individuals and controls. RESULTS: We not only found the expected significant DNA methylation differences in the FMR1 promoter and 5(′) UTR, we also saw that these changes inverse in the FMR1 gene body. Importantly, we found no other differentially methylated loci throughout the remainder of the genome, indicating the aberrant methylation of FMR1 in FXS is locus-specific. CONCLUSIONS: This study provides a comprehensive methylation profile of FXS and helps refine our understanding of the mechanisms behind FMR1 silencing.
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spelling pubmed-35991972013-03-17 Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus Alisch, Reid S Wang, Tao Chopra, Pankaj Visootsak, Jeannie Conneely, Karen N Warren, Stephen T BMC Med Genet Research Article BACKGROUND: Fragile X syndrome (FXS) is a common form of inherited intellectual disability caused by an expansion of CGG repeats located in the 5(′) untranslated region (UTR) of the FMR1 gene, which leads to hypermethylation and silencing of this locus. Although a dramatic increase in DNA methylation of the FMR1 full mutation allele is well documented, the extent to which these changes affect DNA methylation throughout the rest of the genome has gone unexplored. METHODS: Here we examined genome-wide methylation in both peripheral blood (N = 62) and induced pluripotent stem cells (iPSCs; N = 10) from FXS individuals and controls. RESULTS: We not only found the expected significant DNA methylation differences in the FMR1 promoter and 5(′) UTR, we also saw that these changes inverse in the FMR1 gene body. Importantly, we found no other differentially methylated loci throughout the remainder of the genome, indicating the aberrant methylation of FMR1 in FXS is locus-specific. CONCLUSIONS: This study provides a comprehensive methylation profile of FXS and helps refine our understanding of the mechanisms behind FMR1 silencing. BioMed Central 2013-01-29 /pmc/articles/PMC3599197/ /pubmed/23356558 http://dx.doi.org/10.1186/1471-2350-14-18 Text en Copyright ©2013 Alisch et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Alisch, Reid S
Wang, Tao
Chopra, Pankaj
Visootsak, Jeannie
Conneely, Karen N
Warren, Stephen T
Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus
title Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus
title_full Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus
title_fullStr Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus
title_full_unstemmed Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus
title_short Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus
title_sort genome-wide analysis validates aberrant methylation in fragile x syndrome is specific to the fmr1 locus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599197/
https://www.ncbi.nlm.nih.gov/pubmed/23356558
http://dx.doi.org/10.1186/1471-2350-14-18
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