Population Genetics
Part 6

An examination of the origin and frequency of HD

What explains the variation in HD prevalence around the world?

European migration explains much of the variation in HD prevalence rates around the world. Europeans appear to have carried the HD allele with them wherever they settled: North and South America, Australia, New Zealand, etc. Prevalence rates in these populations resemble those of Europe and represent the highest frequencies of HD in the world. But, if the mutation responsible for HD also originated in Japan and Africa, why are the prevalence rates in those regions so much lower?

One theory holds that the different prevalence rates of HD around the world are due to differences in genetic risk factors. Before we take a look at these risk factors, however, let’s take a closer look at the Huntington gene itself:

There are many different versions, or alleles, of the Huntington gene. Perhaps the most noteworthy variation is in the number of CAG repeats (non-HD alleles have under 35 repeats; HD alleles have over 40). However, there are two other variations in the Huntington gene that we will mention here:

• Variation in the Number of CCG Codon Repeats
  Most people either have either 7 or 10 CCG codon repeats adjacent to their CAG repeats. These alleles are either abbreviated (CCG)7 and (CCG)10 or simply “7” and “10.”
  <fig1>
  <fig2>
• The Presence or Absence of a GAG Codon at Residue 2642
  Huntington genes that have a GAG codon at the specific location in the DNA called “residue 2642” are known as “A alleles;” genes without this codon are known as “B alleles.”
  <fig3>
  <fig4>

Now that we know more about the different Huntington gene alleles, let’s look back at the genetic risk factors that may be responsible for the variation in HD prevalence around the world.

As mentioned in Part 4 above, alleles with a high number of CAG repeats are more likely to be the source of new HD mutations. Interestingly, the B7 allele—the allele that has both the B allele and the (CCG)7 allele—usually has a high number of CAG repeats, while the A10 allele usually has a low number of CAG repeats. It has been suggested, though not proven, that the B allele and the (CCG)7 allele may contribute to the instability and expansion of the CAG repeats.

Populations with a high prevalence of HD (i.e., Europeans and those of European ancestry) have a relatively high number of B7 alleles, which are associated with a high number of CAG repeats. This finding suggests that in these populations, new HD mutations may be more frequent, thus making HD more prevalent.

On the other hand, populations with a low prevalence of HD (i.e., in the populations of Africa, China, Finland, and Japan) have a relatively high number of A10 alleles, which are associated with a low number of CAG repeats. This indicates that new HD mutations may be less frequent in these populations, making HD less prevalent. The (CCG)7 allele is relatively underrepresented in these populations, and the B allele is not even found in Africa and Asia

Therefore, along with European emigration to certain parts of the world, the uneven distribution of certain “at risk” chromosomes may contribute to the geographical variation in HD prevalence rates.

Last Modified: 04/12/2007

An educational product of HOPES, not to be used in place of medical care. For more information about HOPES, click on the Logo. To contact HOPES with comments or questions, click here.