Parallel Analysis of Repeat Expansions
7 affiliations
- 1MGZ-Medical Genetics Center, Munich, Germany
- 2MGZ-Medical Genetics Center, Munich, Germany; Friedrich-Baur-Institute, Department of Neurology, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany
- 3MGZ-Medical Genetics Center, Munich, Germany; Laboratorio de Genética Médica, Instituto de Biomedicina, Facultad de Medicina de Albacete, Universidad de Castilla-La Mancha, Albacete, Spain
- 4Center for Human Genetics and Genomic Medicine, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
- 5MGZ-Medical Genetics Center, Munich, Germany; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München Campus Innenstadt, Munich, Germany
- 6MGZ-Medical Genetics Center, Munich, Germany; Institute of Neurogenomics, Helmholtz Zentrum München GmbH-German Research Center for Environmental Health, Munich, Germany
- 7MGZ-Medical Genetics Center, Munich, Germany; Friedrich-Baur-Institute, Department of Neurology, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München Campus Innenstadt, Munich, Germany. Electronic address: [email protected]
Abstract
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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BibTeX
@article{scholz2026parallel,
title = {{Parallel Analysis of Repeat Expansions}},
author = {Veronika Scholz and Veronika Schönrock and Hannes Erdmann and Vitus Prokosch and Maria Schoedel and Manuela Almus and Mayra Sauer and Veronika Mayer and Eva Breithausen and Inga Van Buren and Christine Dineiger and M Golibrzuch and Minerva Montero-Hernández and Annette Lischka and Katja Eggermann and Caroline Heintz and Ariane Hallermayr and Teresa Neuhann and Elke Holinski‐Feder and Angela Abicht and Anna Benet‐Pagès and Morghan C. Lucas},
journal = {Journal of Molecular Diagnostics},
year = {2026},
month = sep,
doi = {10.1016/j.jmoldx.2026.04.007},
url = {https://doi.org/10.1016/j.jmoldx.2026.04.007},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Parallel Analysis of Repeat Expansions
AU - Veronika Scholz
AU - Veronika Schönrock
AU - Hannes Erdmann
AU - Vitus Prokosch
AU - Maria Schoedel
AU - Manuela Almus
AU - Mayra Sauer
AU - Veronika Mayer
AU - Eva Breithausen
AU - Inga Van Buren
AU - Christine Dineiger
AU - M Golibrzuch
AU - Minerva Montero-Hernández
AU - Annette Lischka
AU - Katja Eggermann
AU - Caroline Heintz
AU - Ariane Hallermayr
AU - Teresa Neuhann
AU - Elke Holinski‐Feder
AU - Angela Abicht
AU - Anna Benet‐Pagès
AU - Morghan C. Lucas
PY - 2026
DA - 2026/09/15
JO - Journal of Molecular Diagnostics
DO - 10.1016/j.jmoldx.2026.04.007
UR - https://doi.org/10.1016/j.jmoldx.2026.04.007
AB - 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.
SN - 1525-1578
SN - 1943-7811
ER -