Trinucleotide expansion in disease: why is there a length threshold?

Curr Opin Genet Dev. 2014 Jun;26:131-40. doi: 10.1016/j.gde.2014.07.003. Epub 2014 Oct 1.

Abstract

Trinucleotide repeats (TNRs) expansion disorders are severe neurodegenerative and neuromuscular disorders that arise from inheriting a long tract (30-50 copies) of a trinucleotide unit within or near an expressed gene (Figure 1a). The mutation is referred to as 'trinucleotide expansion' since the number of triplet units in a mutated gene is greater than the number found in the normal gene. Expansion becomes obvious once the number of repeating units passes a critical threshold length, but what happens at the threshold to render the repeating tract unstable? Here we discuss DNA-dependent and RNA-dependent models by which a particular DNA length permits a rapid transition to an unstable state.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • DNA / genetics
  • DNA / metabolism
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Models, Genetic
  • Neurodegenerative Diseases / genetics*
  • Neuromuscular Diseases / genetics*
  • RNA / genetics
  • RNA / metabolism
  • Trinucleotide Repeat Expansion / genetics*
  • Trinucleotide Repeats / genetics*

Substances

  • RNA
  • DNA