Detection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing

Abstract More than 900 variants have been described in the GLA gene. Some intronic variants and copy number variants in GLA can cause Fabry disease but will not be detected by classical Sanger sequence. We aimed to design and validate a method for sequencing the GLA gene using long-read Oxford Nanop...

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Autores principales:	Albina Nowak, Omer Murik, Tzvia Mann, David A. Zeevi, Gheona Altarescu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d6d1074245474c7a9812c07b568074f0
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spelling	oai:doaj.org-article:d6d1074245474c7a9812c07b568074f02021-11-21T12:16:15ZDetection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing10.1038/s41598-021-01749-72045-2322https://doaj.org/article/d6d1074245474c7a9812c07b568074f02021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01749-7https://doaj.org/toc/2045-2322Abstract More than 900 variants have been described in the GLA gene. Some intronic variants and copy number variants in GLA can cause Fabry disease but will not be detected by classical Sanger sequence. We aimed to design and validate a method for sequencing the GLA gene using long-read Oxford Nanopore sequencing technology. Twelve Fabry patients were blindly analyzed, both by conventional Sanger sequence and by long-read sequencing of a 13 kb PCR amplicon. We used minimap2 to align the long-read data and Nanopolish and Sniffles to call variants. All the variants detected by Sanger (including a deep intronic variant) were also detected by long-read sequencing. One patient had a deletion that was not detected by Sanger sequencing but was detected by the new technology. Our long-read sequencing-based method was able to detect missense variants and an exonic deletion, with the added advantage of intronic analysis. It can be used as an efficient and cost-effective tool for screening and diagnosing Fabry disease.Albina NowakOmer MurikTzvia MannDavid A. ZeeviGheona AltarescuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Albina Nowak Omer Murik Tzvia Mann David A. Zeevi Gheona Altarescu Detection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing
description	Abstract More than 900 variants have been described in the GLA gene. Some intronic variants and copy number variants in GLA can cause Fabry disease but will not be detected by classical Sanger sequence. We aimed to design and validate a method for sequencing the GLA gene using long-read Oxford Nanopore sequencing technology. Twelve Fabry patients were blindly analyzed, both by conventional Sanger sequence and by long-read sequencing of a 13 kb PCR amplicon. We used minimap2 to align the long-read data and Nanopolish and Sniffles to call variants. All the variants detected by Sanger (including a deep intronic variant) were also detected by long-read sequencing. One patient had a deletion that was not detected by Sanger sequencing but was detected by the new technology. Our long-read sequencing-based method was able to detect missense variants and an exonic deletion, with the added advantage of intronic analysis. It can be used as an efficient and cost-effective tool for screening and diagnosing Fabry disease.
format	article
author	Albina Nowak Omer Murik Tzvia Mann David A. Zeevi Gheona Altarescu
author_facet	Albina Nowak Omer Murik Tzvia Mann David A. Zeevi Gheona Altarescu
author_sort	Albina Nowak
title	Detection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing
title_short	Detection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing
title_full	Detection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing
title_fullStr	Detection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing
title_full_unstemmed	Detection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing
title_sort	detection of single nucleotide and copy number variants in the fabry disease-associated gla gene using nanopore sequencing
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d6d1074245474c7a9812c07b568074f0
work_keys_str_mv	AT albinanowak detectionofsinglenucleotideandcopynumbervariantsinthefabrydiseaseassociatedglageneusingnanoporesequencing AT omermurik detectionofsinglenucleotideandcopynumbervariantsinthefabrydiseaseassociatedglageneusingnanoporesequencing AT tzviamann detectionofsinglenucleotideandcopynumbervariantsinthefabrydiseaseassociatedglageneusingnanoporesequencing AT davidazeevi detectionofsinglenucleotideandcopynumbervariantsinthefabrydiseaseassociatedglageneusingnanoporesequencing AT gheonaaltarescu detectionofsinglenucleotideandcopynumbervariantsinthefabrydiseaseassociatedglageneusingnanoporesequencing
_version_	1718419152882892800

Detection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing

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