ReviewGenome research2025
The additional diagnostic yield of long-read sequencing in undiagnosed rare diseases.
Review in Genome research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Current translational perspectives for diagnosis and individualized therapy in rare genetic diseases.Communications medicine · 2026Review
- Clinical Epigenomics in Rare Diseases: Interpreting DNA Methylation Episignatures.Molecular genetics & genomic medicine · 2026Review
- Detecting pathogenic structural variation in families with undiagnosed rare disease in a national genome project.European journal of human genetics : EJHG · 2026Article
- Length Matters: Toward the Clinical Adoption of Long-Read Sequencing.Annals of laboratory medicine · 2026Article
- Spectrum of Hereditary Neuropathies in Adult Patients From Serbia.Journal of the peripheral nervous system : JPNS · 2026Article
- Long-Read Sequencing in CKD Diagnostics: Breaking Genomic Barriers and Expanding Global Inclusion.Kidney international reports · 2026Review
- Identifying genetic causes and establishing a diagnostic approach for WES-negative pediatric population with neurodevelopmental disorder.European journal of human genetics : EJHG · 2026Article
- Article
- Unraveling missing variants through target capture-based long-read sequencing in autosomal recessive disorders.European journal of human genetics : EJHG · 2026Article
- Benchmarking long-read variant sensitivity across ONT and PacBio platforms using known clinically reported variants in a cohort of critically ill newborns.medRxiv : the preprint server for health sciences · 2026Article
- Copy number variant analysis by exome sequencing is an effective approach to optimize diagnostic yield for developmental disorders-the DDD-Africa study.European journal of human genetics : EJHG · 2026Article
- The importance and clinical utility of reanalysis of exome and genome sequencing data.Kidney research and clinical practice · 2026Article
- Near-perfect genome sequencing in medical genetics.Nature genetics · 2026Review
- Genetic insights into congenital and infantile nephrotic syndrome: predicting severity and informing care.Pediatric nephrology (Berlin, Germany) · 2026Article
- Implementation of a medical genomics program for rare diseases in Uruguay.Orphanet journal of rare diseases · 2026Article
- Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing.medRxiv : the preprint server for health sciences · 2026Article
- The utility and advantages of exome and genome sequencing in pediatric kidney disease diagnosis.Childhood kidney diseases · 2026Review
- Short-read genome sequencing at population scale: diagnostic insights from 2317 patients.European journal of human genetics : EJHG · 2026Article
- Determinants of haplotype phasing accuracy in long-read human genome sequencing.bioRxiv : the preprint server for biology · 2026Article
- Sensitivity of HiFi long-read genome sequencing for difficult-to-detect pathogenic variants when applied to real-world clinical laboratory samples.American journal of human genetics · 2026Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Long-read sequencing (LRS) is a promising technology positioned to study the significant proportion of rare diseases (RDs) that remain undiagnosed as it addresses many of the limitations of short-read sequencing, detecting and clarifying additional disease-associated variants that may be missed by the current standard diagnostic workflow for RDs. Some key areas where additional diagnostic yields may be realized include: (1) detection and resolution of structural variants (SVs); (2) detection and characterization of tandem repeat expansions; (3) coverage of regions of high sequence similarity; (4) variant phasing; (5) the use of de novo genome assemblies for reference-based or graph genome variant detection; and (6) epigenetic and transcriptomic evaluations. Examples from over 50 studies support that the main areas of added diagnostic yield currently lie in SV detection and characterization, repeat expansion assessment, and phasing (with or without DNA methylation information). Several emerging studies applying LRS in cohorts of undiagnosed RDs also demonstrate that LRS can boost diagnostic yields following negative standard-of-care clinical testing and provide an added yield of 7%-17% following negative short-read genome sequencing. With this evidence of improved diagnostic yield, we discuss the incorporation of LRS into the diagnostic care pathway for undiagnosed RDs, including current challenges and considerations, with the ultimate goal of ending the diagnostic odyssey for countless individuals with RDs.
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