Analysis of Triplet-Repeat DNA by Capillary Electrophoresis

Abstract

Recently, much attention has been focused on triplet-repeat expansions on the human genome, because they are reported to cause a number of neurodegenerative diseases such as the familial mental retardation, myotonic dystrophy, autosomal dominant diseases, or Huntington disease, which are so called triplet-repeat diseases (1,2). A hallmark of most of these diseases is the phenomenon of “anticipation,” which are not easily explained by Mendel’s Laws of genetic inheritance. This phenomenon includes a parental sex bias and a “decrease in the age at onset of the disease” or severity of the disease in consecutive generations due to the tendency of the unstable triplet repeat to lengthen when passed from one generation to the next. The expansion of the triplet-repeat element is associated with the defect, in which the extent of the expansion roughly correlates with the severity of the disease symptoms. The tripletrepeat element expansions are not stable, and it is unclear precisely how the expansions are directly associated with triplet-repeat diseases. Although several expansions encode enlarged polyglutamine tracts within their encoded protein, which might be expected to alter either the charge density and pI, or the folded structure of the protein, the mechanism for the etiology and progression of most of these diseases is not yet understood.