Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization - Archive ouverte HAL Access content directly
Journal Articles Molecular Genetics & Genomic Medicine Year : 2020

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

Nicolas Chatron
Laurence Faivre

Abstract

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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Dates and versions

hal-04383042 , version 1 (18-06-2024)

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Kévin Uguen, Claire Jubin, Yannis Duffourd, Claire Bardel, Valérie Malan, et al.. Genome sequencing in cytogenetics: Comparison of short‐read and linked‐read approaches for germline structural variant detection and characterization. Molecular Genetics & Genomic Medicine, 2020, 8 (3), pp.1-10. ⟨10.1002/mgg3.1114⟩. ⟨hal-04383042⟩
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