All About Mutations
Part 8

What it means to have a mutation and what role mutations play in Huntington’s disease.

HD has repeat expansions, but shouldn’t repeat contractions occur as well?

It seems that for every one thing in life, there always exists an opposite: For black there is white, for truth there are lies, and for rain there is sun. It makes perfect sense, then, to assume that expansions in HD should also have an opposite, contractions. While contractions do in fact occur, they are less common than one might expect. As discussed in Part 4, one real-life study of HD showed that 52.1% of parent-child transmissions result in expansion, compared to only 18% for contraction. The big discrepancy between the two phenomena may be explained by the number of CAGs in the repeating region of the parent’s Huntington gene: A study of a large group of adults with 36 or fewer CAG repeats in the Huntington gene showed that both expansions and contractions became more frequent with increasing numbers of CAGs. For example, an individual with 35 CAGs had a higher chance of causing an expansion or a contraction than an individual with 30 CAGs. However, beyond 36 CAGs, while expansions continued to be more frequent with an increasing number of repeats, contractions became less frequent. For instance, while the DNA of someone with 70 CAGs is more likely to undergo an expansion than the DNA of someone with 40 CAGs, the DNA of the person with 70 CAGs is actually less likely to undergo a contraction than the DNA of a person with 40. These data suggest that parents with more than 36 CAGs may help account for the higher number of expansions than contractions in the real-life data.

It is unclear why exactly there appears to be a barrier for contraction at 36 CAGs. It is interesting to note, however, that 36 is also the number of CAGs that places a person at the bottom of the intermediate range for risk of HD (If a person has between 36 and 40 copies of CAG, he may or may not develop HD. See Table A-1.) Of the people without HD, those in the intermediate range (with 36 to 40 CAGs) are more likely to have children with expansions than are people who have fewer than 36 CAGs.

Last Modified: 1-28-04

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