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Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions

A recessive Short Tandem Repeat expansion in RFC1 has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a frequent cause of late onset ataxia and sensory neuropathy. The usual procedure for sizing these expansions is based on Souther...

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Autores principales: Facchini, Stefano, Dominik, Natalia, Manini, Arianna, Efthymiou, Stephanie, Currò, Riccardo, Rugginini, Bianca, Vegezzi, Elisa, Quartesan, Ilaria, Perrone, Benedetta, Kutty, Shahedah Koya, Galassi Deforie, Valentina, Schnekenberg, Ricardo P., Abati, Elena, Pichiecchio, Anna, Valente, Enza Maria, Tassorelli, Cristina, Reilly, Mary M., Houlden, Henry, Bugiardini, Enrico, Cortese, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605474/
https://www.ncbi.nlm.nih.gov/pubmed/37892228
http://dx.doi.org/10.3390/biom13101546
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author Facchini, Stefano
Dominik, Natalia
Manini, Arianna
Efthymiou, Stephanie
Currò, Riccardo
Rugginini, Bianca
Vegezzi, Elisa
Quartesan, Ilaria
Perrone, Benedetta
Kutty, Shahedah Koya
Galassi Deforie, Valentina
Schnekenberg, Ricardo P.
Abati, Elena
Pichiecchio, Anna
Valente, Enza Maria
Tassorelli, Cristina
Reilly, Mary M.
Houlden, Henry
Bugiardini, Enrico
Cortese, Andrea
author_facet Facchini, Stefano
Dominik, Natalia
Manini, Arianna
Efthymiou, Stephanie
Currò, Riccardo
Rugginini, Bianca
Vegezzi, Elisa
Quartesan, Ilaria
Perrone, Benedetta
Kutty, Shahedah Koya
Galassi Deforie, Valentina
Schnekenberg, Ricardo P.
Abati, Elena
Pichiecchio, Anna
Valente, Enza Maria
Tassorelli, Cristina
Reilly, Mary M.
Houlden, Henry
Bugiardini, Enrico
Cortese, Andrea
author_sort Facchini, Stefano
collection PubMed
description A recessive Short Tandem Repeat expansion in RFC1 has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a frequent cause of late onset ataxia and sensory neuropathy. The usual procedure for sizing these expansions is based on Southern Blotting (SB), a time-consuming and a relatively imprecise technique. In this paper, we compare SB with Optical Genome Mapping (OGM), a method for detecting Structural Variants (SVs) based on the measurement of distances between fluorescently labelled probes, for the diagnosis of RFC1 CANVAS and disease spectrum. The two methods are applied to 17 CANVAS patients’ blood samples and resulting sizes compared, showing a good agreement. Further, long-read sequencing is used for two patients to investigate the agreement of sizes with either SB or OGM. Our study concludes that OGM represents a viable alternative to SB, allowing for a simpler technique, a more precise sizing of the expansion and ability to expand analysis of SV in the entire genome as opposed to SB which is a locus specific method.
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spelling pubmed-106054742023-10-28 Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions Facchini, Stefano Dominik, Natalia Manini, Arianna Efthymiou, Stephanie Currò, Riccardo Rugginini, Bianca Vegezzi, Elisa Quartesan, Ilaria Perrone, Benedetta Kutty, Shahedah Koya Galassi Deforie, Valentina Schnekenberg, Ricardo P. Abati, Elena Pichiecchio, Anna Valente, Enza Maria Tassorelli, Cristina Reilly, Mary M. Houlden, Henry Bugiardini, Enrico Cortese, Andrea Biomolecules Article A recessive Short Tandem Repeat expansion in RFC1 has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a frequent cause of late onset ataxia and sensory neuropathy. The usual procedure for sizing these expansions is based on Southern Blotting (SB), a time-consuming and a relatively imprecise technique. In this paper, we compare SB with Optical Genome Mapping (OGM), a method for detecting Structural Variants (SVs) based on the measurement of distances between fluorescently labelled probes, for the diagnosis of RFC1 CANVAS and disease spectrum. The two methods are applied to 17 CANVAS patients’ blood samples and resulting sizes compared, showing a good agreement. Further, long-read sequencing is used for two patients to investigate the agreement of sizes with either SB or OGM. Our study concludes that OGM represents a viable alternative to SB, allowing for a simpler technique, a more precise sizing of the expansion and ability to expand analysis of SV in the entire genome as opposed to SB which is a locus specific method. MDPI 2023-10-19 /pmc/articles/PMC10605474/ /pubmed/37892228 http://dx.doi.org/10.3390/biom13101546 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Facchini, Stefano
Dominik, Natalia
Manini, Arianna
Efthymiou, Stephanie
Currò, Riccardo
Rugginini, Bianca
Vegezzi, Elisa
Quartesan, Ilaria
Perrone, Benedetta
Kutty, Shahedah Koya
Galassi Deforie, Valentina
Schnekenberg, Ricardo P.
Abati, Elena
Pichiecchio, Anna
Valente, Enza Maria
Tassorelli, Cristina
Reilly, Mary M.
Houlden, Henry
Bugiardini, Enrico
Cortese, Andrea
Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions
title Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions
title_full Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions
title_fullStr Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions
title_full_unstemmed Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions
title_short Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions
title_sort optical genome mapping enables detection and accurate sizing of rfc1 repeat expansions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605474/
https://www.ncbi.nlm.nih.gov/pubmed/37892228
http://dx.doi.org/10.3390/biom13101546
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