regard, several disorders of human cognition can be at least partly attributed to dysfunction in
the mechanisms that underlie epigenetic marking of the genome. One example is Rett syndrome,
an inherited, X-linked disease that is due, in the main, to inactivating mutations of MeCP2 (21).
Fragile X syndrome, the most commonly inherited form of mental retardation, is brought about
by an abnormal expansion of repeated trinucleotide sequences within one of two different fragile
X genes: FMR1 and FMR2. Both FMR1 and FMR2 contain a polymorphic trinucleotide repeat—
CGG and CCG, respectively—in their 5 untranslated regions responsible for the loss of gene
expression. Expansion of these repeats results in hypermethylation of these regions and flanking
CpG islands, leading to transcriptional silencing of the FMR and surrounding genes (118, 119).
The most widespread of senile dementias, Alzheimer’s disease, is associated with altered DNA
methylation in both laboratory animal models and human postmortem brain tissue (120, 121).