Mutational bias provides a model for the evolution of Huntington's disease and predicts a general increase in disease prevalence
article
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.
Topics
AlleleComputer simulationEvolutionGene mutationGenotypeHumanHuman cellHuntington choreaMarker geneMutation rateNatural selectionPredictionPrevalenceTandem repeatAnimalBase SequenceComputer SimulationDNA PrimersEvolutionGene FrequencyHaplotypesHuntington DiseaseLinkage DisequilibriumMeiosisMinisatellite RepeatsModels, GeneticMolecular Sequence DataMutationOligodeoxyribonucleotidesPrimates
TNO Identifier
280580
ISSN
1061-4036
Source
Nature Genetics, 7(4), pp. 525-530.
Pages
525-530
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