دورية أكاديمية
Haplotype information of large neuromuscular disease genes provided by linked-read sequencing has a potential to increase diagnostic yield
| العنوان: | Haplotype information of large neuromuscular disease genes provided by linked-read sequencing has a potential to increase diagnostic yield |
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| المؤلفون: | Johanna Lehtonen, Anna-Maija Sulonen, Henrikki Almusa, Vilma-Lotta Lehtokari, Mridul Johari, Aino Palva, Anna H. Hakonen, Kirmo Wartiovaara, Anna-Elina Lehesjoki, Bjarne Udd, Carina Wallgren-Pettersson, Katarina Pelin, Marco Savarese, Janna Saarela |
| المصدر: | Scientific Reports, Vol 14, Iss 1, Pp 1-11 (2024) |
| بيانات النشر: | Nature Portfolio, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract Rare or novel missense variants in large genes such as TTN and NEB are frequent in the general population, which hampers the interpretation of putative disease-causing biallelic variants in patients with sporadic neuromuscular disorders. Often, when the first initial genetic analysis is performed, the reconstructed haplotype, i.e. phasing information of the variants is missing. Segregation analysis increases the diagnostic turnaround time and is not always possible if samples from family members are lacking. To overcome this difficulty, we investigated how well the linked-read technology succeeded to phase variants in these large genes, and whether it improved the identification of structural variants. Linked-read sequencing data of nemaline myopathy, distal myopathy, and proximal myopathy patients were analyzed for phasing, single nucleotide variants, and structural variants. Variant phasing was successful in the large muscle genes studied. The longest continuous phase blocks were gained using high-quality DNA samples with long DNA fragments. Homozygosity increased the number of phase blocks, especially in exome sequencing samples lacking intronic variation. In our cohort, linked-read sequencing added more information about the structural variation but did not lead to a molecular genetic diagnosis. The linked-read technology can support the clinical diagnosis of neuromuscular and other genetic disorders. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-024-54866-4 |
| URL الوصول: | https://doaj.org/article/43e5137fe16b43bb8cfbbc8eaa443ea1 |
| رقم الأكسشن: | edsdoj.43e5137fe16b43bb8cfbbc8eaa443ea1 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-024-54866-4 |