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Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization

BACKGROUND: Structural variants (SVs) include copy number variants (CNVs) and apparently balanced chromosomal rearrangements (ABCRs). Genome sequencing (GS) enables SV detection at base‐pair resolution, but the use of short‐read sequencing is limited by repetitive sequences, and long‐read approaches...

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Autores principales: Uguen, Kévin, Jubin, Claire, Duffourd, Yannis, Bardel, Claire, Malan, Valérie, Dupont, Jean‐Michel, El Khattabi, Laila, Chatron, Nicolas, Vitobello, Antonio, Rollat‐Farnier, Pierre‐Antoine, Baulard, Céline, Lelorch, Marc, Leduc, Aurélie, Tisserant, Emilie, Tran Mau‐Them, Frédéric, Danjean, Vincent, Delepine, Marc, Till, Marianne, Meyer, Vincent, Lyonnet, Stanislas, Mosca‐Boidron, Anne‐laure, Thevenon, Julien, Faivre, Laurence, Thauvin‐Robinet, Christel, Schluth‐Bolard, Caroline, Boland, Anne, Olaso, Robert, Callier, Patrick, Romana, Serge, Deleuze, Jean‐François, Sanlaville, Damien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057128/
https://www.ncbi.nlm.nih.gov/pubmed/31985172
http://dx.doi.org/10.1002/mgg3.1114
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author Uguen, Kévin
Jubin, Claire
Duffourd, Yannis
Bardel, Claire
Malan, Valérie
Dupont, Jean‐Michel
El Khattabi, Laila
Chatron, Nicolas
Vitobello, Antonio
Rollat‐Farnier, Pierre‐Antoine
Baulard, Céline
Lelorch, Marc
Leduc, Aurélie
Tisserant, Emilie
Tran Mau‐Them, Frédéric
Danjean, Vincent
Delepine, Marc
Till, Marianne
Meyer, Vincent
Lyonnet, Stanislas
Mosca‐Boidron, Anne‐laure
Thevenon, Julien
Faivre, Laurence
Thauvin‐Robinet, Christel
Schluth‐Bolard, Caroline
Boland, Anne
Olaso, Robert
Callier, Patrick
Romana, Serge
Deleuze, Jean‐François
Sanlaville, Damien
author_facet Uguen, Kévin
Jubin, Claire
Duffourd, Yannis
Bardel, Claire
Malan, Valérie
Dupont, Jean‐Michel
El Khattabi, Laila
Chatron, Nicolas
Vitobello, Antonio
Rollat‐Farnier, Pierre‐Antoine
Baulard, Céline
Lelorch, Marc
Leduc, Aurélie
Tisserant, Emilie
Tran Mau‐Them, Frédéric
Danjean, Vincent
Delepine, Marc
Till, Marianne
Meyer, Vincent
Lyonnet, Stanislas
Mosca‐Boidron, Anne‐laure
Thevenon, Julien
Faivre, Laurence
Thauvin‐Robinet, Christel
Schluth‐Bolard, Caroline
Boland, Anne
Olaso, Robert
Callier, Patrick
Romana, Serge
Deleuze, Jean‐François
Sanlaville, Damien
author_sort Uguen, Kévin
collection PubMed
description BACKGROUND: Structural variants (SVs) include copy number variants (CNVs) and apparently balanced chromosomal rearrangements (ABCRs). Genome sequencing (GS) enables SV detection at base‐pair resolution, but the use of short‐read sequencing is limited by repetitive sequences, and long‐read approaches are not yet validated for diagnosis. Recently, 10X Genomics proposed Chromium, a technology providing linked‐reads to reconstruct long DNA fragments and which could represent a good alternative. No study has compared short‐read to linked‐read technologies to detect SVs in a constitutional diagnostic setting yet. The aim of this work was to determine whether the 10X Genomics technology enables better detection and comprehension of SVs than short‐read WGS. METHODS: We included 13 patients carrying various SVs. Whole genome analyses were performed using paired‐end HiSeq X sequencing with (linked‐read strategy) or without (short‐read strategy) Chromium library preparation. Two different bioinformatic pipelines were used: Variants are called using BreakDancer for short‐read strategy and LongRanger for long‐read strategy. Variant interpretations were first blinded. RESULTS: The short‐read strategy allowed diagnosis of known SV in 10/13 patients. After unblinding, the linked‐read strategy identified 10/13 SVs, including one (patient 7) missed by the short‐read strategy. CONCLUSION: In conclusion, regarding the results of this study, 10X Genomics solution did not improve the detection and characterization of SV.
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spelling pubmed-70571282020-03-12 Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization Uguen, Kévin Jubin, Claire Duffourd, Yannis Bardel, Claire Malan, Valérie Dupont, Jean‐Michel El Khattabi, Laila Chatron, Nicolas Vitobello, Antonio Rollat‐Farnier, Pierre‐Antoine Baulard, Céline Lelorch, Marc Leduc, Aurélie Tisserant, Emilie Tran Mau‐Them, Frédéric Danjean, Vincent Delepine, Marc Till, Marianne Meyer, Vincent Lyonnet, Stanislas Mosca‐Boidron, Anne‐laure Thevenon, Julien Faivre, Laurence Thauvin‐Robinet, Christel Schluth‐Bolard, Caroline Boland, Anne Olaso, Robert Callier, Patrick Romana, Serge Deleuze, Jean‐François Sanlaville, Damien Mol Genet Genomic Med Method BACKGROUND: Structural variants (SVs) include copy number variants (CNVs) and apparently balanced chromosomal rearrangements (ABCRs). Genome sequencing (GS) enables SV detection at base‐pair resolution, but the use of short‐read sequencing is limited by repetitive sequences, and long‐read approaches are not yet validated for diagnosis. Recently, 10X Genomics proposed Chromium, a technology providing linked‐reads to reconstruct long DNA fragments and which could represent a good alternative. No study has compared short‐read to linked‐read technologies to detect SVs in a constitutional diagnostic setting yet. The aim of this work was to determine whether the 10X Genomics technology enables better detection and comprehension of SVs than short‐read WGS. METHODS: We included 13 patients carrying various SVs. Whole genome analyses were performed using paired‐end HiSeq X sequencing with (linked‐read strategy) or without (short‐read strategy) Chromium library preparation. Two different bioinformatic pipelines were used: Variants are called using BreakDancer for short‐read strategy and LongRanger for long‐read strategy. Variant interpretations were first blinded. RESULTS: The short‐read strategy allowed diagnosis of known SV in 10/13 patients. After unblinding, the linked‐read strategy identified 10/13 SVs, including one (patient 7) missed by the short‐read strategy. CONCLUSION: In conclusion, regarding the results of this study, 10X Genomics solution did not improve the detection and characterization of SV. John Wiley and Sons Inc. 2020-01-27 /pmc/articles/PMC7057128/ /pubmed/31985172 http://dx.doi.org/10.1002/mgg3.1114 Text en © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Method
Uguen, Kévin
Jubin, Claire
Duffourd, Yannis
Bardel, Claire
Malan, Valérie
Dupont, Jean‐Michel
El Khattabi, Laila
Chatron, Nicolas
Vitobello, Antonio
Rollat‐Farnier, Pierre‐Antoine
Baulard, Céline
Lelorch, Marc
Leduc, Aurélie
Tisserant, Emilie
Tran Mau‐Them, Frédéric
Danjean, Vincent
Delepine, Marc
Till, Marianne
Meyer, Vincent
Lyonnet, Stanislas
Mosca‐Boidron, Anne‐laure
Thevenon, Julien
Faivre, Laurence
Thauvin‐Robinet, Christel
Schluth‐Bolard, Caroline
Boland, Anne
Olaso, Robert
Callier, Patrick
Romana, Serge
Deleuze, Jean‐François
Sanlaville, Damien
Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization
title Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization
title_full Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization
title_fullStr Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization
title_full_unstemmed Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization
title_short Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization
title_sort genome sequencing in cytogenetics: comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057128/
https://www.ncbi.nlm.nih.gov/pubmed/31985172
http://dx.doi.org/10.1002/mgg3.1114
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