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Hypomethylation of an Expanded FMR1 Allele Is Not Associated with a Global DNA Methylation Defect
- Source :
- The American Journal of Human Genetics. 65(5):1375-1386
- Publication Year :
- 1999
- Publisher :
- Elsevier BV, 1999.
-
Abstract
- Summary The vast majority of fragile-X full mutations are heavily methylated throughout the expanded CGG repeat and the surrounding CpG island. Hypermethylation initiates and/or stabilizes transcriptional inactivation of the FMR1 gene, which causes the fragile X–syndrome phenotype characterized, primarily, by mental retardation. The relation between repeat expansion and hypermethylation is not well understood nor is it absolute, as demonstrated by the identification of nonretarded males who carry hypomethylated full mutations. To better characterize the methylation pattern in a patient who carries a hypomethylated full mutation of ∼60–700 repeats, we have evaluated methylation with the McrBC endonuclease, which allows analysis of numerous sites in the FMR1 CpG island, including those located within the CGG repeat. We report that the expanded-repeat region is completely free of methylation in this full-mutation male. Significantly, this lack of methylation appears to be specific to the expanded FMR1 CGG-repeat region, because various linked and unlinked repetitive-element loci are methylated normally. This finding demonstrates that the lack of methylation in the expanded CGG-repeat region is not associated with a global defect in methylation of highly repeated DNA sequences. We also report that de novo methylation of the expanded CGG-repeat region does not occur when it is moved via microcell-mediated chromosome transfer into a de novo methylation-competent mouse embryonal carcinoma cell line.
- Subjects :
- Adult
Male
congenital, hereditary, and neonatal diseases and abnormalities
X Chromosome
Restriction Mapping
Nerve Tissue Proteins
Hypomethylation
Biology
Methylation
03 medical and health sciences
Fragile X Mental Retardation Protein
Mice
Epigenetics of physical exercise
Trinucleotide Repeats
Alu Elements
Genetics
Animals
Humans
Genetics(clinical)
Allele
Deoxyribonucleases, Type II Site-Specific
Repetitive elements
FMR1
Genetics (clinical)
X chromosome
Alleles
Cells, Cultured
CGG
030304 developmental biology
0303 health sciences
030305 genetics & heredity
Genetic transfer
RNA-Binding Proteins
DNA Restriction Enzymes
Articles
DNA Methylation
Molecular biology
nervous system diseases
CpG site
Fragile X Syndrome
DNA methylation
Fragile X
CpG Islands
Trinucleotide repeat expansion
Subjects
Details
- ISSN :
- 00029297
- Volume :
- 65
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- The American Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....b66e004b6329b66933208f57c9048e6b
- Full Text :
- https://doi.org/10.1086/302628