Population genetics of wild-type CAG repeats in the Machado-Joseph disease gene in Portugal

Hum Hered. 2005;60(3):156-63. doi: 10.1159/000090035. Epub 2005 Dec 6.


Objective: To gain insights on the molecular mechanisms of mutation that led to the emergence of expanded alleles in the MJD gene, by studying the behavior of wild-type alleles and testing the association of its distribution with the representation of the disease.

Methods: The number of CAG motifs in the MJD gene was determined in a representative sample of 1000 unrelated individuals. Associations between the repeat size and the epidemiological representation of MJD were tested.

Results: The allelic profile of the total sample was in the normal range (13-41 repeats), with mode (CAG)23. No intermediate alleles were present. Allelic size distribution showed a negative skew. The correlation between the epidemiological representation of MJD in each district and the frequency of small, medium and large normal alleles was not significant. Further correlations performed grouping the districts also failed to produce significant results.

Conclusions: The absence of association between the size of the repeats and the representation of MJD demonstrates that prevalence is not an indirect reflection of the frequency of large normal alleles. Globally the results obtained are in accordance with a model that postulates the occurrence of a few mutations on the basis of most of the MJD cases worldwide.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxin-3
  • Demography
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genetics, Population*
  • Humans
  • Machado-Joseph Disease / epidemiology*
  • Machado-Joseph Disease / genetics*
  • Models, Genetic
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Portugal / epidemiology
  • Repressor Proteins / genetics*
  • Trinucleotide Repeat Expansion / genetics*


  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • ATXN3 protein, human
  • Ataxin-3