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Scholz, V.* ; Schönrock, V.* ; Erdmann, H.* ; Prokosch, V.* ; Schoedel, M.* ; Almus, M.* ; Sauer, M.* ; Mayer, V.* ; Breithausen, E.* ; van Buren, I.* ; Dineiger, C.* ; Golibrzuch, M.* ; Montero-Hernández, M.* ; Lischka, A.* ; Eggermann, K.* ; Heintz, C.* ; Hallermayr, A.* ; Neuhann, T.* ; Holinski-Feder, E.* ; Abicht, A.* ; Benet-Pages, A. ; Lucas, M.C.*

Parallel analysis of repeat expansions.

J. Mol. Diagn. 28, 811-824 (2026)
Postprint Research data DOI
Open Access Hybrid
Hereditary ataxias, caused by expansions of short tandem repeats, are difficult to diagnose using traditional PCR and Southern blot methods, which struggle to detect complex repeat expansions and cannot assess repeat interruptions or methylation. An updated Clinical Nanopore Cas9-Targeted Sequencing workflow is presented for analyzing repeat expansions, now compatible with the Oxford Nanopore Technologies R10 flow cell. The workflow incorporates the Oxford Nanopore Technologies wf-human-variation Epi2Me workflow, including the Straglr tool to analyze base-called reads, ensuring compatibility with past, current, and future sequencing chemistries. It expands the number of genes analyzed from 10 to 27 and introduces new gene panels for ataxia, myopathy, neurodegeneration, and amyotrophic lateral sclerosis/motor neuron disease. Validated with Coriell reference and clinical samples, this method improves the analysis of pathogenic repeat expansions, providing deeper insights into repeat structures while addressing the limitations of traditional approaches. In this work, the use of multiplexing, Flongle flow cells, and single-gene targeting were explored as alternatives to panel-based approaches in the Clinical Nanopore Cas9-Targeted Sequencing workflow, finding that only single-gene targeting provides compatibility and reliable performance.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 1525-1578
e-ISSN 1943-7811
Journal Journal of Molecular Diagnostics
Quellenangaben Volume: 28, Issue: 11, Pages: 811-824 Article Number: , Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Institiute of Neurogenomics (ING)
Institute of Network Biology (INET)