التفاصيل البيبلوغرافية
| العنوان: |
Splicing Outcomes of 5′ Splice Site GT>GC Variants That Generate Wild-Type Transcripts Differ Significantly Between Full-Length and Minigene Splicing Assays |
| المؤلفون: |
Jin-Huan Lin, Hao Wu, Wen-Bin Zou, Emmanuelle Masson, Yann Fichou, Gerald Le Gac, David N. Cooper, Claude Férec, Zhuan Liao, Jian-Min Chen |
| المصدر: |
Frontiers in Genetics, Vol 12 (2021) |
| بيانات النشر: |
Frontiers Media S.A., 2021. |
| سنة النشر: |
2021 |
| المجموعة: |
LCC:Genetics |
| مصطلحات موضوعية: |
aberrant transcript, full-length gene splicing assay, genetic variant, minigene splicing assay, splice site, SpliceAI, Genetics, QH426-470 |
| الوصف: |
Combining data derived from a meta-analysis of human disease-associated 5′ splice site GT>GC (i.e., +2T>C) variants and a cell culture-based full-length gene splicing assay (FLGSA) of forward engineered +2T>C substitutions, we recently estimated that ∼15–18% of +2T>C variants can generate up to 84% wild-type transcripts relative to their wild-type counterparts. Herein, we analyzed the splicing outcomes of 20 +2T>C variants that generate some wild-type transcripts in two minigene assays. We found a high discordance rate in terms of the generation of wild-type transcripts, not only between FLGSA and the minigene assays but also between the different minigene assays. In the pET01 context, all 20 wild-type minigene constructs generated the expected wild-type transcripts; of the 20 corresponding variant minigene constructs, 14 (70%) generated wild-type transcripts. In the pSPL3 context, only 18 of the 20 wild-type minigene constructs generated the expected wild-type transcripts whereas 8 of the 18 (44%) corresponding variant minigene constructs generated wild-type transcripts. Thus, in the context of a particular type of variant, we raise awareness of the limitations of minigene splicing assays and emphasize the importance of sequence context in regulating splicing. Whether or not our findings apply to other types of splice-altering variant remains to be investigated. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1664-8021 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fgene.2021.701652/full; https://doaj.org/toc/1664-8021 |
| DOI: |
10.3389/fgene.2021.701652 |
| URL الوصول: |
https://doaj.org/article/920a9cae8edb476b95ec85d518580099 |
| رقم الانضمام: |
edsdoj.920a9cae8edb476b95ec85d518580099 |
| قاعدة البيانات: |
Directory of Open Access Journals |
Full Text Finder