مؤتمر
P442: CAGE expression profiling of the human iPS-derivedneurons carrying mutations in the C9orf72
| العنوان: | P442: CAGE expression profiling of the human iPS-derivedneurons carrying mutations in the C9orf72 |
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| المؤلفون: | Dhingra, Ashutosh, Pyz, Elwira, Heutink, Peter, Simon Sanchez, Javier, Castillo Lizardo, Melissa Gissel, Theurer, Y., Schöls, Ludger, Timmann-Braun, D., Prudlo, J., Synofzik, M., Rizzu, Patrizia |
| المصدر: | Journal of neurochemistry 138(Supplement 1), 414 (2016). ; 10th International Conference on Frontotemporal Dementias, Munich, Germany, 2016-08-31 - 2016-09-02 |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | info:eu-repo/classification/ddc/610 |
| جغرافية الموضوع: | DE |
| الوصف: | A hexanucleotide (GGGGCC)n repeat expansion in the noncod-ing region of the C9orf72 gene is the most common pathogenicmutation in patients affected with frontotemporal dementia (FTD) oramyotrophic lateral sclerosis (ALS). The exact function of C9orf72remains largely unknown. We have identified two point mutations inthe C9orf72 gene. The first patient with clinical ALS carried (hg19)Chr9:27556694 C to A resulting in the following amino acid changeP319Q, and the second patient carrying Chr9:27566700 G to A(R140Q) presents with ataxia but not ALS/FTD. The mutations arehighly conserved and predicted to be damaging using insilicopredictions (PolyPhen-2 and MutationTaster) but definite evidencefor their pathogenicity is lacking. We therefore generated inducedpluripotent stem cells (iPS) from both patients and characterized thelines on a molecular level. The iPS cells from the point mutationsgrew normally with morphology similar to hES cells and can bedifferentiatied into neurons with similar potential to control linesand as expected do not show RNA foci characteristic hallmarks ofrepeat expansion carriers. To investigate global transcriptionalchanges we prepared Cap Analysis of Gene Expression (CAGE)libraries from RNA of iPS and iPS differentiated neurons, derivedfrom both point mutations, C9orf72 repeat expansion carriers andcontrols. CAGE libraries were, sequenced on Illumina HiSeq2500 atan average depth of 15 million reads. The resulting data wasprocessed through an in-house CAGE pipeline.We observed a general transcriptional downregulation in therepeat expansion carriers when compared to controls. We areintegrating the CAGE data from the repeat expansion carriers withthe point mutations carrier cells with the aim to build gene networkmodels using Ingenuity Pathway Analysis and will validate ourfindings of relevant pathways via perturbation of the key genes inour iPS lines. |
| نوع الوثيقة: | conference object |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/issn/0022-3042; https://pub.dzne.de/record/145521Test; https://pub.dzne.de/search?p=id:%22DZNE-2020-00855%22Test |
| الإتاحة: | https://pub.dzne.de/record/145521Test https://pub.dzne.de/search?p=id:%22DZNE-2020-00855%22Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.8B64CF7F |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |