دورية أكاديمية
أعرض في EDS

Characterization of full-length CNBP expanded alleles in myotonic dystrophy type 2 patients by Cas9-mediated enrichment and nanopore sequencing.

التفاصيل البيبلوغرافية
العنوان: Characterization of full-length CNBP expanded alleles in myotonic dystrophy type 2 patients by Cas9-mediated enrichment and nanopore sequencing.
المؤلفون: Alfano M; Department of Biotechnology, University of Verona, Verona, Italy., De Antoni L; Department of Biotechnology, University of Verona, Verona, Italy., Centofanti F; Department of Biomedicine and Prevention, Medical Genetics Section, University of Rome Tor Vergata, Rome, Italy., Visconti VV; Department of Biomedicine and Prevention, Medical Genetics Section, University of Rome Tor Vergata, Rome, Italy., Maestri S; Department of Biotechnology, University of Verona, Verona, Italy., Degli Esposti C; Department of Biotechnology, University of Verona, Verona, Italy., Massa R; Department of Systems Medicine (Neurology), University of Rome Tor Vergata, Rome, Italy., D'Apice MR; Laboratory of Medical Genetics, Tor Vergata Hospital, Rome, Italy., Novelli G; Department of Biomedicine and Prevention, Medical Genetics Section, University of Rome Tor Vergata, Rome, Italy.; IRCCS Neuromed, Via Atinense, Molise, Italy.; Department of Pharmacology, School of Medicine, University of Nevada Reno, Reno, United States., Delledonne M; Department of Biotechnology, University of Verona, Verona, Italy.; Genartis s.r.l., Via P. Mascagni, Castel D'azzano, Italy., Botta A; Department of Biomedicine and Prevention, Medical Genetics Section, University of Rome Tor Vergata, Rome, Italy., Rossato M; Department of Biotechnology, University of Verona, Verona, Italy.; Genartis s.r.l., Via P. Mascagni, Castel D'azzano, Italy.
المصدر: ELife [Elife] 2022 Aug 26; Vol. 11. Date of Electronic Publication: 2022 Aug 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Myotonic Dystrophy*/genetics , Nanopore Sequencing*, Alleles ; CRISPR-Cas Systems ; Genetic Association Studies ; Humans ; RNA-Binding Proteins/genetics
مستخلص: Myotonic dystrophy type 2 (DM2) is caused by CCTG repeat expansions in the CNBP gene, comprising 75 to >11,000 units and featuring extensive mosaicism, making it challenging to sequence fully expanded alleles. To overcome these limitations, we used PCR-free Cas9-mediated nanopore sequencing to characterize CNBP repeat expansions at the single-nucleotide level in nine DM2 patients. The length of normal and expanded alleles can be assessed precisely using this strategy, agreeing with traditional methods, and revealing the degree of mosaicism. We also sequenced an entire ~50 kbp expansion, which has not been achieved previously for DM2 or any other repeat-expansion disorders. Our approach precisely counted the repeats and identified the repeat pattern for both short interrupted and uninterrupted alleles. Interestingly, in the expanded alleles, only two DM2 samples featured the expected pure CCTG repeat pattern, while the other seven presented also TCTG blocks at the 3' end, which have not been reported before in DM2 patients, but confirmed hereby with orthogonal methods. The demonstrated approach simultaneously determines repeat length, structure/motif, and the extent of somatic mosaicism, promising to improve the molecular diagnosis of DM2 and achieve more accurate genotype-phenotype correlations for the better stratification of DM2 patients in clinical trials.
Competing Interests: MA, LD, FC, VV, SM, CD, RM, MD, GN, AB No competing interests declared, MD is a partner of Genartis srl, MR is a partner of Genartis srl, Verona
(© 2022, Alfano, De Antoni et al.)
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فهرسة مساهمة: Keywords: CNBP gene; Cas9-mediated enrichment; genetics; genomics; human; myotonic dystrophy type 2; nanopore sequencing; repeat expansion
المشرفين على المادة: 0 (CNBP protein, human)
0 (RNA-Binding Proteins)
تواريخ الأحداث: Date Created: 20220826 Date Completed: 20220913 Latest Revision: 20220913
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9462847
DOI: 10.7554/eLife.80229
PMID: 36018009
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.80229