Related Experiment Video

Updated: Jul 16, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease

L Djoussé1, B Knowlton, M Hayden

  • 1Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

American Journal of Medical Genetics. Part A
|June 5, 2003
PubMed

Insights

The size of the normal Huntington allele may influence Huntington disease (HD) onset. Larger normal repeats might mitigate disease severity in individuals with expanded CAG repeats.

Area of Science:

  • Genetics
  • Neuroscience
  • Molecular Biology

Background:

  • Huntington disease (HD) is a neurodegenerative disorder linked to CAG repeat expansion in the HD gene.
  • CAG repeat size is known to inversely correlate with age at onset (AO) in HD patients.

Purpose of the Study:

  • To investigate if the normal Huntington allele size interacts with the expanded CAG repeat size to influence the age at onset (AO) of Huntington disease (HD).

Main Methods:

  • Analysis of data from two independent cohorts: the New England Huntington Disease Center Without Walls (NEHD) and HD-MAPS.
  • Statistical analysis to assess the interaction between normal and expanded CAG repeat sizes and their effect on AO.

Main Results:

  • Evidence of an interaction between expanded and unexpanded CAG repeat sizes influencing AO was found in both cohorts (P = 0.08 and 0.07).
  • This interaction was statistically significant when both cohorts were combined (P = 0.012).
  • The estimated heritability of AO residuals, after accounting for repeats and their interaction, was 0.56.

Conclusions:

  • An increase in normal allele size may potentially mitigate disease expression in HD patients with large expanded CAG repeats.
  • These findings highlight a potential modifier role for the normal Huntington allele in HD pathogenesis.

More Related Videos

Measuring RAN Peptide Toxicity in C. elegans10:49

Measuring RAN Peptide Toxicity in C. elegans

Published on: April 30, 2020

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System10:52

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

Published on: December 10, 2021

Related Concept Videos

Genetic Lingo01:11

Genetic Lingo

Overview
Multiple Allele Traits01:49

Multiple Allele Traits

The Concept of Multiple Allelism
Hardy-Weinberg Principle01:49

Hardy-Weinberg Principle

Diploid organisms have two alleles of each gene, one from each parent, in their somatic cells. Therefore, each individual contributes two alleles to the gene pool of the population. The gene pool of a population is the sum of every allele of all genes within that population and has some degree of variation. Genetic variation is typically expressed as a relative frequency, which is the percentage of the total population that has a given allele, genotype or phenotype.In the early 20th century,...
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...
Human Genetics01:28

Human Genetics

Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
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,...