Open AccessGenome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization
Author(s) -
Uguen Kévin,
Jubin Claire,
Duffourd Yannis,
Bardel Claire,
Malan Valérie,
Dupont JeanMichel,
El Khattabi Laila,
Chatron Nicolas,
Vitobello Antonio,
RollatFarnier PierreAntoine,
Baulard Céline,
Lelorch Marc,
Leduc Aurélie,
Tisserant Emilie,
Tran MauThem Frédéric,
Danjean Vincent,
Delepine Marc,
Till Marianne,
Meyer Vincent,
Lyonnet Stanislas,
MoscaBoidron Annelaure,
Theve Julien,
Faivre Laurence,
ThauvinRobinet Christel,
SchluthBolard Caroline,
Boland Anne,
Olaso Robert,
Callier Patrick,
Romana Serge,
Deleuze JeanFrançois,
Sanlaville Damien
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1114
Subject(s) - computational biology , genome , genomics , dna sequencing , whole genome sequencing , genetics , computer science , biology , gene
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.