Population Genetics
Part 9

An examination of the origin and frequency of HD

Conclusion

As this section shows, the history of the HD allele in human populations has not been fully unraveled. While geneticists have some idea where the allele originated, and how it spread through human migration, they are still trying to understand how the allele has been maintained at such high frequencies in certain parts of the world and what the genetic risks are of developing a new mutation. Although the study of population genetics may at first seem to be a matter of purely historical interest, clues revealed by this kind of inquiry will surely help clinicians better understand the HD mutation and Huntington’s disease itself.

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-J. Czaja, 7/25/03

For further reading:

1. Almqvist, E, et al. “Ancestral differences in the distribution of the delta 2642 glutamic acid polymorphism is associated with varying CAG repeat lengths on normal chromosomes: Insights into the genetic evolution of Huntington disease.” Human Molecular Genetics, February 1995, 4 (2): 207-14.
   A technical paper on the GAG deletion, the CAG repeat lengths, and their distributions around the world.
2. Almqvist E, et al. “Geographical distribution of haplotypes in Swedish families with Huntington’s disease.” Human Genetics, August 1994, 94 (2): 124-8.
   A technical paper on the Huntington gene alleles found in Sweden and their implications for the multiple-origin hypothesis in Europe.
3. Andrew, SE and MR Hayden. “Origins and evolution of Huntington disease chromosomes.” Neurodegeneration, September 1995, 4 (3): 239-44.
   A technical paper on the relationship between CAG repeat lengths and development of new HD alleles.
4. Harper, PS. “The epidemiology of Huntington’s disease.” Human Genetics, 1992, 89: 365-76.
   A fairly easy-to-read paper on the epidemiology of HD around the world as of 1992. Though a bit outdated, this is probably the best overall review article on this list.
5. “Genetic background of Huntington’s disease in Croatia: molecular analysis of CAG, CCG, and Δ2642 (E2642del) polymorphisms.” Human Mutation, September 2002, 20 (3): 233.
   A technical but clear explanation of the CAG, CCG, and GAG deletion patterns found in Croatia. Includes useful discussion of the varying Huntington gene alleles around the world.
6. Morrison, PJ, et al. “The epidemiology of Huntington’s disease in Northern Ireland.” Journal of Medical Genetics, 1995, 32: 524-30.
   A technical paper that discusses the prevalence of HD in Northern Ireland, the theory of HD origin in Europe, and the increased fertility among HD patients.
7. Pridmore, SA and GC Adams. “The fertility of HD-affected individuals in Tasmania.” Australian and New Zealand Journal of Psychiatry, June 1991, 25 (2): 262-4.
   A fairly technical paper on the increased fertility among presymptomatic HD patients in Tasmania, Australia.
8. Rubinsztein, DC, et al. “Haplotype analysis of the delta 2642 and (CAG)n polymorphisms in the Huntington’s disease (HD) gene provides an explanation for an apparent ‘founder’ HD haplotype.” Human Molecular Genetics, February 1995, 4 (2): 203-6.
   A technical paper on the GAG deletion, the CAG repeat lengths, and the chromosomes that are at risk for CAG codon expansion.
9. Squitieri, F, et al. “DNA haplotype analysis of Huntington disease reveals clues to the origins and mechanisms of CAG expansion and reasons for geographic variations of prevalence.” Human Molecular Genetics, December 1994, 3 (12): 2103-14.
   A technical paper on the different Huntington gene alleles and their different ancestries around the world.
10. Stine, OC and KD Smith. “The estimation of selection coefficients in Afrikaners: Huntington Disease, Prophyria Variegata, and Lipoid Proteinosis.” American Journal of Human Genetics, 1990, 46: 452-458.
    A technical paper discussing the decreased fertility found among Afrikaners with HD.
11. Walker, DA, et al. “Huntington’s chorea in South Wales: mutation, fertility, and genetic fitness.” Journal of Medical Genetics, 6 February 1983, 20 (1): 12-17.
    A fairly technical paper on the increased fertility and fitness among presymptomatic HD patients in South Wales.

Last Modified: 08/04/2008

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