Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Huntington Disease l: Introduction

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,...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Genetic or pharmacological disruption of the MSH3 Y245/K246 IDL binding pocket slows CAG repeat expansion.

NAR molecular medicine·2026

Same author

Recurrent Copy Number Variants and Psychiatric Outcomes in the Context of Polygenic Scores.

JAMA psychiatry·2026

Same author

Predicted brain-regional gene expression patterns in individuals living with Alzheimer's disease.

Neurobiology of aging·2026

Same author

Combining polygenic risk scores to understand genetic liability to physical-mental health multimorbidity in UK Biobank.

Human molecular genetics·2026

Same author

Analysis of rare coding variants in schizophrenia-associated genes and generalised cognition in the UK Biobank.

Molecular psychiatry·2026

Same author

Neurodevelopmental copy-number variants increase risk of internalizing and cardiometabolic multimorbidity: Findings from the UK Biobank.

American journal of human genetics·2026

Search research articles

Related Experiment Video

Updated: Jul 9, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

FAN1 modifies Huntington's disease progression by stabilizing the expanded HTT CAG repeat.

Robert Goold¹, Michael Flower¹, Davina Hensman Moss¹

¹UCL Huntington's Disease Centre,Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London,Queen Square, London WC1N 3BG, UK.

Human Molecular Genetics

|October 26, 2018

Summary

FAN1 protein may protect against Huntington's disease (HD) progression. Increased FAN1 expression is linked to delayed onset and slower disease advancement in HD patients, offering new therapeutic targets.

More Related Videos

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Published on: June 27, 2018

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

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

Published on: December 10, 2021

Related Experiment Videos

Last Updated: Jul 9, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Published on: June 27, 2018

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

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

Published on: December 10, 2021

Area of Science:

Genetics
Neuroscience
Molecular Biology

Background:

Huntington's disease (HD) is an inherited neurodegenerative disorder.
CAG repeat expansion in the huntingtin (HTT) gene is the primary cause of HD.
Genetic variations influence HD's age at onset (AAO) and progression rate.

Purpose of the Study:

Investigate the role of FANCD2- and FANCI-associated nuclease 1 (FAN1) in HD pathogenesis.
Determine if FAN1 expression levels correlate with HD patient outcomes.
Elucidate the mechanism by which FAN1 influences CAG repeat instability in HD.

Main Methods:

Genome-wide association studies to identify genetic modifiers of HD.
Analysis of FAN1 expression in relation to AAO and disease progression.
Cellular assays using human cells, patient-derived stem cells, and neurons to assess CAG repeat expansion.
Biochemical experiments to study FAN1 binding to HTT CAG repeat DNA.

Main Results:

Higher FAN1 expression is significantly associated with delayed AAO and slower HD progression.
FAN1 overexpression reduced CAG repeat expansion in mutant HTT exon 1.
FAN1 knockdown led to increased CAG repeat expansion in patient-derived cells.
FAN1 binds to expanded HTT CAG repeat DNA, and its nuclease activity is not required for protection.

Conclusions:

FAN1 acts as a protective factor against CAG repeat expansion in HD.
FAN1 influences somatic expansion of the CAG repeat via a nuclease-independent mechanism.
FAN1 represents a potential therapeutic target for Huntington's disease and other triplet repeat disorders.