Analysis of (CAG)n size heterogeneity in somatic and sperm cell DNA from intermediate and expanded Huntington disease gene carriers

Hum Mutat. 1997;10(6):458-64. doi: 10.1002/(SICI)1098-1004(1997)10:6<458::AID-HUMU7>3.0.CO;2-9.

Abstract

The length of the CAG repeat responsible for Huntington disease has been analysed by two PCR methods in blood and sperm DNA of 13 expansion carriers, two carriers of intermediate alleles, and four normal subjects. The two methods consistently confirmed size heterogeneity, more pronounced in sperm and confined to the CAG stretch. Based on densitometric scanning of films, four indexes addressed to different features of the PCR pattern were used to quantitate mosaicism. These revealed strong correlations with CAG size and intergenerational instability. However, mosaicism did not show a greater similarity in sibs who shared the same HD chromosome, nor was correlated with instability in the proband's pedigree. Our data do not support the hypothesis that cis-acting factors play a major role in the instability and leave the CAG size per se as the major determinant of sperm cell CAG instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • DNA / analysis*
  • DNA / blood
  • DNA / genetics
  • Heterozygote*
  • Humans
  • Huntington Disease / genetics*
  • Male
  • Middle Aged
  • Mosaicism / genetics
  • Pedigree
  • Polymerase Chain Reaction / methods
  • Spermatozoa / chemistry*
  • Trinucleotide Repeats / genetics*

Substances

  • DNA

Grants and funding