دورية أكاديمية
HPO-driven virtual gene panel: a new efficient approach in molecular autopsy of sudden unexplained death
| العنوان: | HPO-driven virtual gene panel: a new efficient approach in molecular autopsy of sudden unexplained death |
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| المؤلفون: | Ulrike Schön, Anna Holzer, Andreas Laner, Stephanie Kleinle, Florentine Scharf, Anna Benet-Pagès, Oliver Peschel, Elke Holinski-Feder, Isabel Diebold |
| المصدر: | BMC Medical Genomics, Vol 14, Iss 1, Pp 1-9 (2021) |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Internal medicine LCC:Genetics |
| مصطلحات موضوعية: | Sudden unexplained death, Molecular autopsy, HPO, Variant interpretation, Whole exome sequencing, Internal medicine, RC31-1245, Genetics, QH426-470 |
| الوصف: | Abstract Background Molecular autopsy represents an efficient tool to save the diagnosis in up to one-third of sudden unexplained death (SUD). A defined gene panel is usually used for the examination. Alternatively, it is possible to carry out a comprehensive genetic assessment (whole exome sequencing, WES), which also identifies rare, previously unknown variants. The disadvantage is that a dramatic number of variants must be assessed to identify the causal variant. To improve the evaluation of WES, the human phenotype ontology (HPO) annotation is used internationally for deep phenotyping in the field of rare disease. However, a HPO-based evaluation of WES in SUD has not been described before. Methods We performed WES in tissue samples from 16 people after SUD. Instead of a fixed gene panel, we defined a set of HPO terms and thus created a flexible “virtual gene panel”, with the advantage, that recently identified genes are automatically associated by HPO terms in the HPO database. Results We obtained a mean value of 68,947 variants per sample. Stringent filtering ended up in a mean value of 276 variants per sample. Using the HPO-driven virtual gene panel we developed an algorithm that prioritized 1.4% of the variants. Variant interpretation resulted in eleven potentially causative variants in 16 individuals. Conclusion Our data introduce an effective diagnostic procedure in molecular autopsy of SUD with a non-specific clinical phenotype. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1755-8794 |
| العلاقة: | https://doaj.org/toc/1755-8794Test |
| DOI: | 10.1186/s12920-021-00946-7 |
| الوصول الحر: | https://doaj.org/article/08a11a22f2ea42599a42a39be34627aaTest |
| رقم الانضمام: | edsdoj.08a11a22f2ea42599a42a39be34627aa |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17558794 |
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| DOI: | 10.1186/s12920-021-00946-7 |