Haplotype background, repeat length evolution, and Huntington's disease.

摘要

Warby et al. present fascinating data on the haplotype background of chromosomes carrying the Huntington's disease (HD [MIM 143100]) mutation and the length distribution of the CAG repeat for different haplotypes within the general population. One of their conclusions is that ds-elements are likely to represent a major predisposing element in HD expansion. Here, I use evolutionary modeling of the CAG repeat length distribution within populations to argue that the distribution of CAG repeat length and disease incidence in different haplotypes,. can be explained by founder events, each of which involved expansion of repeats to lengths that are classified as normal by HD investigators (<28 repeats). There is therefore no need to invoke cis-element polymorphism within the human population.