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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
Journal of Medical Genetics
|July 31, 2007
Summary
Huntington disease (HD) CAG repeat instability in sperm is mainly predicted by repeat length. Genetic factors, not parent age, influence repeat changes during transmission, with offspring sex impacting maternal transmissions.
Area of Science:
- Genetics
- Molecular Biology
- Neurodegenerative Diseases
Background:
- Huntington disease (HD) is characterized by CAG repeat instability during intergenerational transmission.
- This instability is particularly evident in male transmissions, reflected in sperm DNA CAG repeat variability.
Purpose of the Study:
- To investigate factors influencing CAG repeat instability in sperm DNA from male HD gene carriers.
- To analyze transmission instability in a large Venezuelan cohort, examining parental and offspring factors.
Main Methods:
- Analysis of 112 sperm DNAs from male HD gene carriers.
- Investigation of 184 father-offspring and 311 mother-offspring transmissions within a Venezuelan pedigree.
- Statistical analysis to identify correlations between repeat instability and various factors.
Main Results:
- CAG repeat length is the primary predictor of sperm DNA repeat variability.
- Repeat instability was not correlated with donor age or affectedness status.
- Transmission instability depended on the transmitting parent's sex and CAG repeat length, but not parental age or birth order.
- Maternal transmissions showed sex-specific effects, with repeat expansion in male offspring and contraction in female offspring.
Conclusions:
- Sibling-sibling correlation suggests a role for genetic factors in intergenerational CAG repeat instability.
- Parental age and birth order do not significantly impact HD CAG repeat instability during transmission.
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