ArticleBrain : a journal of neurology2021
Long-read targeted sequencing uncovers clinicopathological associations for C9orf72-linked diseases.
Article in Brain : a journal of neurology, 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.
- PAICS mediates DNA damage and cerebellar neuronal loss in C9orf72 amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Article
- Unified long-read panel for Parkinson's and repeat expansion disorders.NPJ Parkinson's disease · 2026Article
- Somatic mosaicism in ALS and FTD identifies focal mutations associated with widespread degeneration.Nature genetics · 2026Article
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.International journal of molecular sciences · 2025Review
- Amyotrophic lateral sclerosis caused by hexanucleotide repeat expansions in C9orf72: from genetics to therapeutics.The Lancet. Neurology · 2025Review
- Navigating triplet repeats sequencing: concepts, methodological challenges and perspective for Huntington's disease.Nucleic acids research · 2025Review
- Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion.Molecular neurodegeneration · 2024Article
- Leveraging the power of long reads for targeted sequencing.Genome research · 2024Review
- Single-Molecule Sequencing of theBio-protocol · 2024Article
- Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.Nature reviews. Genetics · 2024Review
- Abundant transcriptomic alterations in the human cerebellum of patients with a C9orf72 repeat expansion.Acta neuropathologica · 2024Article
- Validated assays for the quantification of C9orf72 human pathology.Scientific reports · 2024Article
- Review
- Advances in sequencing technologies for amyotrophic lateral sclerosis research.Molecular neurodegeneration · 2023Review
- 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
- Evidence of cerebellar TDP-43 loss of function in FTLD-TDP.Acta neuropathologica communications · 2022Article
- Profiling the Genome-Wide Landscape of Short Tandem Repeats by Long-Read Sequencing.Frontiers in genetics · 2022Article
- Uncovering Essential Tremor Genetics: The Promise of Long-Read Sequencing.Frontiers in neurology · 2022Review
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Authors and funding
22 authors.
Funding
Abstract
To examine the length of a hexanucleotide expansion in C9orf72, which represents the most frequent genetic cause of frontotemporal lobar degeneration and motor neuron disease, we employed a targeted amplification-free long-read sequencing technology: No-Amp sequencing. In our cross-sectional study, we assessed cerebellar tissue from 28 well-characterized C9orf72 expansion carriers. We obtained 3507 on-target circular consensus sequencing reads, of which 814 bridged the C9orf72 repeat expansion (23%). Importantly, we observed a significant correlation between expansion sizes obtained using No-Amp sequencing and Southern blotting (P = 5.0 × 10-4). Interestingly, we also detected a significant survival advantage for individuals with smaller expansions (P = 0.004). Additionally, we uncovered that smaller expansions were significantly associated with higher levels of C9orf72 transcripts containing intron 1b (P = 0.003), poly(GP) proteins (P = 1.3 × 10- 5), and poly(GA) proteins (P = 0.005). Thorough examination of the composition of the expansion revealed that its GC content was extremely high (median: 100%) and that it was mainly composed of GGGGCC repeats (median: 96%), suggesting that expanded C9orf72 repeats are quite pure. Taken together, our findings demonstrate that No-Amp sequencing is a powerful tool that enables the discovery of relevant clinicopathological associations, highlighting the important role played by the cerebellar size of the expanded repeat in C9orf72-linked diseases.
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