Methylation & Trinucleotide Repeat Disorders

Certain disease states occur as a result of increases in the length of specific three base repeat sections in the genome. These special “repeat regions” are prior to the information or coding region of the DNA. These trinucleotide repeats are involved in certain disorders such as Friedreich’s ataxia, Fragile X and Huntington’s disease. We also see a role for trinucleotide  repeats in particular regions of genes that serve regulatory purposes, such as the reelin gene that is involved in myelination. When there is insufficient methylation capacity (mutations in the pathway) there is often not enough methyl groups to bind to these repeat regions, so they are able to multiply. This results in very long repeat sections, much longer than they should be. Studies have shown that inhibition of DNA methylation resulted in a 1000 fold increase in these three base repeat sections. Therefore, decreased DNA methylation results in increases in trinucleotide repeats and increases the risks for particular neurological disorders.