Mutational bias provides a model for the evolution of Huntington's disease and predicts a general increase in disease prevalence

Nat Genet. 1994 Aug;7(4):525-30. doi: 10.1038/ng0894-525.

Abstract

Huntington's disease (HD) correlates with abnormal expansion in a block of CAG repeats in the Huntington's disease gene. We have investigated HD evolution by typing CAG alleles in several human populations and in a variety of primates. We find that human alleles have expanded from a shorter ancestral state and exhibit unusual asymmetric length distributions. Computer simulations are used to show that the human state can be derived readily from a primate ancestor, without the need to invoke natural selection. The key element is a simple length-dependent mutational bias towards longer alleles. Our model can explain a number of empirical observations, and predicts an ever-increasing incidence of HD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Base Sequence
  • Biological Evolution*
  • Computer Simulation
  • DNA Primers / genetics
  • Gene Frequency
  • Haplotypes
  • Humans
  • Huntington Disease / etiology
  • Huntington Disease / genetics*
  • Linkage Disequilibrium
  • Meiosis / genetics
  • Minisatellite Repeats
  • Models, Genetic*
  • Molecular Sequence Data
  • Mutation*
  • Oligodeoxyribonucleotides / genetics
  • Primates

Substances

  • DNA Primers
  • Oligodeoxyribonucleotides