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

BMC Medical Genetics

Stephen T Warren³  Karen N Conneely¹  Jeannie Visootsak³  Pankaj Chopra¹  Tao Wang¹  Reid S Alisch² 

[1] Departments of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA, 30322, USA;Current address: Department of Psychiatry, University of Wisconsin–Madison, Madison, WI, 53719, USA;Departments of Pediatrics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA, 30322, USA

关键词: Fragile X syndrome;    DNA methylation;    Epigenetics;   

Others  :  1177735
DOI  :  10.1186/1471-2350-14-18

 received in 2012-10-23, accepted in 2013-01-25,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Alisch et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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