People with Huntington's disease have HTT genes with more than 37 copies of CAG repeat. The risk of extra copies being generated is higher during sperm formation than during ovum formation. Why is it so?

Interesting fact: People with HD allele inherited from father develop symptoms earlier than if that allele is inherited from mother.


1 Answer 1


Excellent question. The answer is that, in general, there is a higher rate of mutation in spermatogenesis compared to oogenesis. This is because there are more cell divisions during spermatogenesis, which allows for opportunities for mutation.

In addition, repeat diseases like Huntington’s sometimes have a phenomenon known as anticipation. This is when the disease gets phenotypically (and genetically) more severe with each successive generation. The exact molecular basis of this is not completely understood, but it is just well known that DNA polymerase tends to make more mistakes in large repeat regions, causing an expansion of the repeat. Anticipation is not linked to gender, I just wanted to point out that these repeats are prone to mutations that will expand the repeat and cause disease

You can see anticipation in this graph. This example is for Fragile X. The higher the repeat number in the parent, the greater the chance the child develops the disease. The parent doesnt have the disease, but what happens is the repeat mutates and gets expanded to the point where the disease will develop.


So, put these two facts together and you have your answer. A male's sperm tends to have a higher overall mutation rate, and the region responsible for Huntingtons is already prone to disease causing mutations as it is. The result ends up being the disease gets ‘inherited’ more often from the father

Picture from here

  • $\begingroup$ Awesome answer ! Could you tell me what is the difference between total CGG repeat length and pure CGG repeat length ? $\endgroup$
    – biogirl
    Aug 23, 2013 at 2:44
  • $\begingroup$ In fragile X the repeat is CGG. But sometimes there are also AGG repeats as well. Pure counts only the CGG repeats, while total includes both. This paper was trying to find the importance of AGG repeats on the disease $\endgroup$
    – von Mises
    Aug 23, 2013 at 15:41
  • $\begingroup$ If they were trying to find the importance of AGG repeats, then why did they count pure CGG repeats ? $\endgroup$
    – biogirl
    Aug 24, 2013 at 3:04

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