ArticleJournal of Huntington's disease2021
Approaches to Sequence the HTT CAG Repeat Expansion and Quantify Repeat Length Variation.
Article in Journal of Huntington's disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Fluid and Imaging Biomarkers in Huntington's Disease.Current neurology and neuroscience reports · 2026Review
- TRACE: Open-source software for quantifying somatic variation of tandem repeats by capillary electrophoresis.Journal of Huntington's disease · 2026Article
- TRACE: Open-Source Software for Quantifying Somatic Variation of Tandem Repeats by Capillary Electrophoresis.bioRxiv : the preprint server for biology · 2026Article
- Sequence Variants in Small CAG Repeat Expansions of theNeurology · 2026Article
- Interventionally targeting somatic CAG expansions can be a rapid disease-modifying therapeutic avenue: Preclinical evidence.bioRxiv : the preprint server for biology · 2025Article
- Tissue-Specific Effects of the DNA Helicase FANCJ/BRIP1/BACH1 on Repeat Expansion in a Mouse Model of the Fragile X-Related Disorders.International journal of molecular sciences · 2025Article
- Article
- Navigating triplet repeats sequencing: concepts, methodological challenges and perspective for Huntington's disease.Nucleic acids research · 2025Review
- When repetita no-longer iuvant: somatic instability of the CAG triplet in Huntington's disease.Nucleic acids research · 2025Review
- Leveraging the power of long reads for targeted sequencing.Genome research · 2024Review
- Tissue-specific TCF4 triplet repeat instability revealed by optical genome mapping.EBioMedicine · 2024Article
- A CAG repeat threshold for therapeutics targeting somatic instability in Huntington's disease.Brain : a journal of neurology · 2024Article
- Review
- Differential microRNA expression in the SH-SY5Y human cell model as potential biomarkers for Huntington's disease.Frontiers in cellular neuroscience · 2024Article
- High-Depth PRNP Sequencing in Brains With Sporadic Creutzfeldt-Jakob Disease.Neurology. Genetics · 2023Article
- Repeat Detector: versatile sizing of expanded tandem repeats and identification of interrupted alleles from targeted DNA sequencing.NAR genomics and bioinformatics · 2022Article
- Characterization of full-lengtheLife · 2022Article
- The Contribution of Somatic Expansion of the CAG Repeat to Symptomatic Development in Huntington's Disease: A Historical Perspective.Journal of Huntington's disease · 2021Review
- Drugging DNA Damage Repair Pathways for Trinucleotide Repeat Expansion Diseases.Journal of Huntington's disease · 2021Review
- Special Issue: DNA Repair and Somatic Repeat Expansion in Huntington's Disease.Journal of Huntington's disease · 2021Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundHuntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of the HTT CAG repeat. Affected individuals inherit ≥36 repeats and longer alleles cause earlier onset, greater disease severity and faster disease progression. The HTT CAG repeat is genetically unstable in the soma in a process that preferentially generates somatic expansions, the proportion of which is associated with disease onset, severity and progression. Somatic mosaicism of the HTT CAG repeat has traditionally been assessed by semi-quantitative PCR-electrophoresis approaches that have limitations (e.g., no information about sequence variants). Genotyping-by-sequencing could allow for some of these limitations to be overcome.
objectiveTo investigate the utility of PCR sequencing to genotype large (>50 CAGs) HD alleles and to quantify the associated somatic mosaicism.
methodsWe have applied MiSeq and PacBio sequencing to PCR products of the HTT CAG repeat in transgenic R6/2 mice carrying ∼55, ∼110, ∼255 and ∼470 CAGs. For each of these alleles, we compared the repeat length distributions generated for different tissues at two ages.
resultsWe were able to sequence the CAG repeat full length in all samples. However, the repeat length distributions for samples with ∼470 CAGs were biased towards shorter repeat lengths.
conclusionPCR sequencing can be used to sequence all the HD alleles considered, but this approach cannot be used to estimate modal allele size or quantify somatic expansions for alleles ⪢250 CAGs. We review the limitations of PCR sequencing and alternative approaches that may allow the quantification of somatic contractions and very large somatic expansions.
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