Population Genetics
Part 3

An examination of the origin and frequency of HD

Is it common for new HD alleles to arise?

Originally, it was thought that mutations from a non-HD allele to an HD allele were rare and accounted for only a very small proportion of HD cases. On an individual level, new mutations were not considered to be very frequent. (Please note: In this chapter, the term “new mutation” specifically refers to the mutation from a non-HD allele to an HD allele.)

On the population level, it was also assumed that new mutations did not significantly affect the frequency of HD. If an HD allele did develop, researchers thought the HD allele could mutate back to a non-HD allele just as easily – thereby not changing the overall frequency of HD alleles in the population.

However, it turns out that the mutation from a non-HD allele to an HD-allele does occur more often than the reverse.

Researchers realized this biased mutation tendency when they discovered that HD was a type of trinucleotide repeat disorder. In such disorders, a high number of codon repeats is indicative of having the disease. Unfortunately, the expansion of a codon repeat is more likely to happen than the contraction of it – resulting in a relatively higher rate of new HD mutations.

A 1994 study confirmed the idea that codon repeat expansions were common by using computer simulations to investigate the evolution of the HD allele. The simulations suggested that the human HD allele expanded from a shorter non-human primate’s allele – suggesting that there is a mutational bias towards having longer and longer Huntington gene alleles. This study predicted that the expansion of codon repeats will continue and accelerate in the absence of any outside interference and lead to an ever-increasing incidence of HD.

A 2001 study used another approach to analyze genetic disorders in order to measure the rate of new mutation. When this approach was applied to HD, it was estimated that the new mutation rate in each generation was about 10%. In other words, this study suggested that about 10% of all HD cases did not inherit the HD allele from a parent, but received the HD allele from a newly formed mutation.

In British Columbia, another study discovered that of 141 patients with HD, 11 had no family history of HD. All 11 cases had reliable parental information with parents who lived well into old age with no signs of the disease. Thus, this study estimated the new mutation rate to be at least 8%.

Though the “true” new mutation rate for HD is still unclear, current estimates range anywhere from 1% to 14%.

Last Modified: 04/12/2007

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