Rubinsztein D C, Amos W, Leggo J, Goodburn S, Ramesar R S, Old J, Bontrop R, McMahon R, Barton D E, Ferguson-Smith M A
East Anglian Regional Genetics Service Molecular Genetics Laboratory, Addenbrooke's NHS Trust, Cambridge, UK.
Nat Genet. 1994 Aug;7(4):525-30. doi: 10.1038/ng0894-525.
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.
