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Updated: Jun 6, 2025
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Ultra-long Read Sequencing for Whole Genomic DNA Analysis
Published on: March 15, 2019
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Full characterization of unresolved structural variation through long-read sequencing and optical genome mapping
Griet De Clercq1,2, Lies Vantomme1, Barbara Dewaele3
1Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
Scientific Reports
|November 25, 2024
Summary
Long-read sequencing (LRS) and optical genome mapping (OGM) effectively characterize complex structural variants (SVs) in human disease. These advanced methods improve diagnostic yield by resolving previously undetected genetic rearrangements.
Area of Science:
- Genomics
- Human Genetics
- Molecular Biology
Background:
- Structural variants (SVs) are significant causes of human disease but are challenging to characterize due to their size and location in repetitive genomic regions.
- Conventional methods often fail to fully resolve complex SVs, limiting diagnostic capabilities.
Purpose of the Study:
- To evaluate the utility of long-read sequencing (LRS) and optical genome mapping (OGM) for comprehensive structural variant characterization.
- To demonstrate the potential of LRS and OGM as advanced diagnostic tools for identifying cryptic and complex rearrangements.
Main Methods:
- Applied long-read sequencing (LRS) to six individuals with unresolved SVs.
- Utilized optical genome mapping (OGM) on a subset of three complex cases.
- Developed detailed laboratory and bioinformatics workflows for LRS and OGM implementation.
Main Results:
- LRS fully resolved all interrogated SVs at single-basepair resolution, enabling precise molecular diagnoses in two individuals.
- OGM facilitated variant phasing and aided in unraveling complex rearrangements.
- Both methods detected complex and cryptic rearrangements missed by conventional approaches.
Conclusions:
- LRS and OGM are powerful molecular tests for complete SV characterization, offering unprecedented resolution for clinically relevant structural variations.
- These technologies significantly increase diagnostic yield and provide valuable insights into SV formation mechanisms.
- The study provides workflows to support the adoption of LRS and OGM in clinical diagnostic settings.
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