Optical genome mapping enables accurate testing of large repeat expansions
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Le résumé fourni par la source
Short tandem repeats (STRs) are common variations in human genomes that frequently expand or contract, causing genetic disorders, mainly when expanded. Traditional diagnostic methods for identifying these expansions, such as repeat-primed PCR and Southern blotting, are often labor-intensive, locus-specific, and are unable to precisely determine long repeat expansions. Sequencing-based methods, although capable of genome-wide detection, are limited by inaccuracy (short-read technologies) and high associated costs (long-read technologies). This study evaluated optical genome mapping (OGM) as an efficient, accurate approach for measuring STR lengths and assessing somatic stability in 85 samples with known pathogenic repeat expansions in DMPK , CNBP , and RFC1 , causing myotonic dystrophy types 1 and 2 and cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), respectively. Three workflows—manual de novo assembly, local guided assembly (local-GA), and a molecule distance script—were applied, of which the latter two were developed as part of this study to assess the repeat sizes and somatic repeat stability. OGM successfully identified 84/85 (98.8%) of the pathogenic expansions, distinguishing between wild-type and expanded alleles or between two expanded alleles in recessive cases, with greater accuracy than standard of care (SOC) for long repeats and no apparent upper size limit. Notably, OGM detected somatic instability in a subset of DMPK , CNBP , and RFC1 samples. These findings suggest OGM could advance diagnostic accuracy for large repeat expansions, providing a more comprehensive genome-wide assay for repeat expansion disorders by measuring exact repeat lengths and somatic instability across multiple loci simultaneously.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Optical genome mapping enables accurate testing of large repeat expansions
- Date Crossref
- 20/03/2025
- Éditeur
- Cold Spring Harbor Laboratory
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Radboud University Nijmegen pays non établi dans la noticeUniversité ou école supérieure
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Radboud University Medical Center Department of Human Genetics pays non établi dans la noticeOrganisme public
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Radboud Institute for Molecular Life Sciences pays non établi dans la noticeStructure de recherche
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BioNano Genomics (United States) pays non établi dans la noticeEntreprise
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Royal Children's Hospital pays non établi dans la noticeÉtablissement de santé
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The University of Melbourne Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Murdoch Children's Research Institute pays non établi dans la noticeOrganisation à but non lucratif
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Austin Health pays non établi dans la noticeÉtablissement de santé
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South Australia Pathology pays non établi dans la noticeOrganisation à but non lucratif
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South Australian Health and Medical Research Institute pays non établi dans la noticeÉtablissement de santé
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The University of Adelaide Robinson Research Institute and Adelaide Medical School pays non établi dans la noticeUniversité ou école supérieure
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Bionano Genomics Clinical and Scientific Affairs pays non établi dans la noticeÉtablissement de santé
Radboud University Nijmegen, Department of Human Genetics — Radboud University Medical Center et Radboud Institute for Molecular Life Sciences, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.