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Updated: Jul 13, 2026

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System
Published on: December 10, 2021
Factors associated with HD CAG repeat instability in Huntington disease
V C Wheeler1, F Persichetti, S M McNeil
1Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA. wheeler@helix.mgh.harvard.edu
Background:
The Huntington disease (HD) CAG repeat exhibits dramatic instability when transmitted to subsequent generations. The instability of the HD disease allele in male intergenerational transmissions is reflected in the variability of the CAG repeat in DNA from the sperm of male carriers of the HD gene.
Results:
In this study, we used a collection of 112 sperm DNAs from male HD gene-positive members of a large Venezuelan cohort to investigate the factors associated with repeat instability. We confirm previous observations that CAG repeat length is the strongest predictor of repeat-length variability in sperm, but we did not find any correlation between CAG repeat instability and either age at the time of sperm donation or affectedness status. We also investigated transmission instability for 184 father-offspring and 311 mother-offspring pairs in this Venezuelan pedigree. Repeat-length changes were dependent upon the sex of the transmitting parent and parental CAG repeat length but not parental age or birth order. Unexpectedly, in maternal transmissions, repeat-length changes were also dependent upon the sex of the offspring, with a tendency for expansion in male offspring and contraction in female offspring.
Conclusion:
Significant sibling-sibling correlation for repeat instability suggests that genetic factors play a role in intergenerational CAG repeat instability.
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