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.
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Rubinsztein, D., Amos, W., Leggo, J. et al. Mutational bias provides a model for the evolution of Huntington's disease and predicts a general increase in disease prevalence. Nat Genet 7, 525–530 (1994). https://doi.org/10.1038/ng0894-525
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DOI: https://doi.org/10.1038/ng0894-525
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