ArticleMolecular genetics & genomic medicine2019
Evaluation of the detection of GBA missense mutations and other variants using the Oxford Nanopore MinION.
Article in Molecular genetics & genomic medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Decoding the Alphabet Soup: A Practical Guide to Genetic Testing in Hyperkinetic Movement Disorders.Tremor and other hyperkinetic movements (New York, N.Y.) · 2025Pooled it
- Detection of single nucleotide and copy number variants in the Fabry disease-associated GLA gene using nanopore sequencing.Scientific reports · 2021Trial
- Assessing the readiness of Oxford Nanopore sequencing for clinical genomics applications.Genome research · 2026Article
- Protocol of ASPro-PD: a phase 3 trial of ambroxol to slow progression in genetically stratified Parkinson's disease.Journal of neurology · 2026Article
- A systematic assessment of machine learning for structural variant filtering.bioRxiv : the preprint server for biology · 2026Article
- VACmap: an accurate long-read aligner for unraveling complex genomic rearrangements.Nature communications · 2026Article
- The transformative impact of ultra-rapid nanopore sequencing in precision medicine.Frontiers in immunology · 2026Review
- Targeted long-read nanopore sequencing as a complementary approach for detecting STRC variants and distinguishing the STRCP1 pseudogene.Scientific reports · 2025Article
- Severe GBA1 variants drive the GBA1-PD clinical phenotype: implications for counselling and clinical trials.NPJ Parkinson's disease · 2025Article
- Reply to: Is Gauchian genotyping of GBA1 variants reliable?Communications biology · 2025Article
- Accurate bacterial outbreak tracing with Oxford Nanopore sequencing and reduction of methylation-induced errors.Genome research · 2024Article
- Detection of mosaic and population-level structural variants with Sniffles2.Nature biotechnology · 2024Article
- Comprehensive assessment of long-read sequencing platforms and calling algorithms for detection of copy number variation.Briefings in bioinformatics · 2024Article
- Review
- Carrier frequency estimation of pathogenic variants of autosomal recessive and X-linked recessive mendelian disorders using exome sequencing data in 1,642 Thais.BMC medical genomics · 2024Article
- Accurate long-read sequencing identified GBA1 as major risk factor in the Luxembourgish Parkinson's study.NPJ Parkinson's disease · 2023Article
- GBA1 in Parkinson's disease: variant detection and pathogenicity scoring matters.BMC genomics · 2023Article
- PMS2-associated Lynch syndrome: Past, present and future.Frontiers in oncology · 2023Review
- Application of Long-Read Nanopore Sequencing to the Search for Mutations in Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2022Article
- Enhancing Molecular Testing for Effective Delivery of Actionable Gene Diagnostics.Bioengineering (Basel, Switzerland) · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundMutations in GBA cause Gaucher disease when biallelic and are strong risk factors for Parkinson's disease when heterozygous. GBA analysis is complicated by the nearby pseudogene. We aimed to design and validate a method for sequencing GBA using long reads.
methodsWe sequenced GBA on the Oxford Nanopore MinION as an 8.9 kb amplicon from 102 individuals, including patients with Parkinson's and Gaucher diseases. We used NanoOK for quality metrics, NGMLR to align data (after comparing with GraphMap), Nanopolish and Sniffles to call variants, and WhatsHap for phasing.
resultsWe detected all known missense mutations in these samples, including the common p.N409S (N370S) and p.L483P (L444P) in multiple samples, and nine rarer ones, as well as a splicing and a truncating mutation, and intronic SNPs. We demonstrated the ability to phase mutations, confirm compound heterozygosity, and assign haplotypes. We also detected two known risk variants in some Parkinson's patients. Rare false positives were easily identified and filtered, with the Nanopolish quality score adjusted for the number of reads a very robust discriminator. In two individuals carrying a recombinant allele, we were able to detect and fully define it in one carrier, where it included a 55-base pair deletion, but not in another one, suggesting a limitation of the PCR enrichment method. Missense mutations were detected at the correct zygosity, except for the case where the RecNciI one was missed.
conclusionThe Oxford Nanopore MinION can detect missense mutations and an exonic deletion in this difficult gene, with the added advantages of phasing and intronic analysis. It can be used as an efficient research tool, but additional work is required to exclude all recombinants.
Indexed as
Identifiers
What OpenQuestion holds
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.