Related Experiment Video

Updated: Jul 13, 2026

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System
10:52

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
PubMed

Insights

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.
Abstract

More Related Videos

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

Measuring RAN Peptide Toxicity in C. elegans10:49

Measuring RAN Peptide Toxicity in C. elegans

Published on: April 30, 2020

Related Concept Videos

Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
Genetic Lingo01:11

Genetic Lingo

Overview
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
Histone Variants at the Centromere02:30

Histone Variants at the Centromere

Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...