ArticleHuman genetics2021
Resolving misalignment interference for NGS-based clinical diagnostics.
Article in Human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1.Orphanet journal of rare diseases · 2022Guideline
- Identification of an emerging heterozygous variant in KAT6A by whole exome sequencing: a case report.Translational pediatrics · 2026Article
- Artificial intelligence-assisted clinical exome sequencing: Insights and outcomes from 822 pediatric diagnoses.Genetics in medicine open · 2026Article
- Diagnostic yield of expanded carrier screening of a multi-ethnic population in yunnan, China.Scientific reports · 2025Article
- Promises and challenges of genomic newborn screening (NBS) - lessons from public health NBS programs.Pediatric research · 2025Review
- Regional patterns of genetic variants in expanded carrier screening: a next-generation sequencing pilot study in Fujian Province, China.Frontiers in genetics · 2025Article
- Parkinson's disease variant detection and disclosure: PD GENEration, a North American study.Brain : a journal of neurology · 2024Observational
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- Variants located in intron 6 ofHeliyon · 2024Article
- The ever wider clinical spectrum of RMND1-related disorders and limitedness of phenotype-based classifications.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Carrier burden of over 300 diseases in Han Chinese identified by expanded carrier testing of 300 couples using assisted reproductive technology.Journal of assisted reproduction and genetics · 2023Article
- Genetic abnormalities in biopsy-proven, adult-onset hemolytic uremic syndrome and C3 glomerulopathy.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Genetic Etiologies for Chronic Kidney Disease Revealed through Next-Generation Renal Gene Panel.American journal of nephrology · 2022Article
- Variant predictions in congenital adrenal hyperplasia caused by mutations in CYP21A2.Frontiers in pharmacology · 2022Article
- From the patient to the population: Use of genomics for population screening.Frontiers in genetics · 2022Article
- Improved detection of SBDS gene mutation by a new method of next-generation sequencing analysis based on the Chinese mutation spectrum.PloS one · 2022Article
- Accurate Molecular Diagnosis of Gaucher Disease Using Clinical Exome Sequencing as a First-Tier Test.International journal of molecular sciences · 2021Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Next-generation sequencing (NGS) is an incredibly useful tool for genetic disease diagnosis. However, the most commonly used bioinformatics methods for analyzing sequence reads insufficiently discriminate genomic regions with extensive sequence identity, such as gene families and pseudogenes, complicating diagnostics. This problem has been recognized for specific genes, including many involved in human disease, and diagnostic labs must perform additional costly steps to guarantee accurate diagnosis in these cases. Here we report a new data analysis method based on the comparison of read depth between highly homologous regions to identify misalignment. Analyzing six clinically important genes-CYP21A2, GBA, HBA1/2, PMS2, and SMN1-each exhibiting misalignment issues related to homology, we show that our technique can correctly identify potential misalignment events and be used to make appropriate calls. Combined with long-range PCR and/or MLPA orthogonal testing, our clinical laboratory can improve variant calling with minimal additional cost. We propose an accurate and cost-efficient NGS testing procedure that will benefit disease diagnostics, carrier screening, and research-based population studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.