Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1locusReportar como inadecuado

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BMC Medical Genetics

, 14:18

Functional and epigenetics


BackgroundFragile 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.

MethodsHere we examined genome-wide methylation in both peripheral blood N = 62 and induced pluripotent stem cells iPSCs; N = 10 from FXS individuals and controls.

ResultsWe 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.

ConclusionsThis study provides a comprehensive methylation profile of FXS and helps refine our understanding of the mechanisms behind FMR1 silencing.

KeywordsEpigenetics DNA methylation Fragile X syndrome AbbreviationsFXSFragile X syndrome

UTRUntranslated region

CVChorionic villi

hESCsHuman embryonic stem cells

iPSInduced pluripotent stem





βMethylation levels

RPearson correlation coefficient

RITSRNA-induced transcriptional silencing

siRNASmall interfering RNA.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-14-18 contains supplementary material, which is available to authorized users.

Reid S Alisch, Tao Wang contributed equally to this work.

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Autor: Reid S Alisch - Tao Wang - Pankaj Chopra - Jeannie Visootsak - Karen N Conneely - Stephen T Warren


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