دورية أكاديمية
Novel candidate blood-based transcriptional biomarkers of machado-joseph disease
| العنوان: | Novel candidate blood-based transcriptional biomarkers of machado-joseph disease |
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| المؤلفون: | Raposo, M, Bettencourt, C, Maciel, P, Gao, F, Ramos, A, Kazachkova, N, Vasconcelos, J, Kay, T, Rodrigues, AJ, Bettencourt, B, Bruges-Armas, J, Geschwind, D, Coppola, G, Lima, M |
| المصدر: | Movement Disorders, vol 30, iss 7 |
| بيانات النشر: | eScholarship, University of California |
| سنة النشر: | 2015 |
| المجموعة: | University of California: eScholarship |
| مصطلحات موضوعية: | Neurology & Neurosurgery, Clinical Sciences, Human Movement and Sports Sciences, Neurosciences |
| جغرافية الموضوع: | 968 - 975 |
| الوصف: | Background: Machado-Joseph disease (or spinocerebellar ataxia type 3) is a late-onset polyglutamine neurodegenerative disorder caused by a mutation in the ATXN3 gene, which encodes for the ubiquitously expressed protein ataxin-3. Previous studies on cell and animal models have suggested that mutated ataxin-3 is involved in transcriptional dysregulation. Starting with a whole-transcriptome profiling of peripheral blood samples from patients and controls, we aimed to confirm abnormal expression profiles in Machado-Joseph disease and to identify promising up-regulated genes as potential candidate biomarkers of disease status. Methods: The Illumina Human V4-HT12 array was used to measure transcriptome-wide gene expression in peripheral blood samples from 12 patients and 12 controls. Technical validation and validation in an independent set of samples were performed by quantitative real-time polymerase chain reaction (PCR). Results: Based on the results from the microarray, twenty six genes, found to be up-regulated in patients, were selected for technical validation by quantitative real-time PCR (validation rate of 81% for the up-regulation trend). Fourteen of these were further tested in an independent set of 42 patients and 35 controls; 10 genes maintained the up-regulation trend (FCGR3B, CSR2RA, CLC, TNFSF14, SLA, P2RY13, FPR2, SELPLG, YIPF6, and GPR96); FCGR3B, P2RY13, and SELPLG were significantly up-regulated in patients when compared with controls. Conclusions: Our findings support the hypothesis that mutated ataxin-3 is associated with transcription dysregulation, detectable in peripheral blood cells. Furthermore, this is the first report suggesting a pool of up-regulated genes in Machado-Joseph disease that may have the potential to be used for fine phenotyping of this disease. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | qt8pq7j5cf; https://escholarship.org/uc/item/8pq7j5cfTest; https://escholarship.org/content/qt8pq7j5cf/qt8pq7j5cf.pdfTest |
| DOI: | 10.1002/mds.26238 |
| الإتاحة: | https://doi.org/10.1002/mds.26238Test https://escholarship.org/uc/item/8pq7j5cfTest https://escholarship.org/content/qt8pq7j5cf/qt8pq7j5cf.pdfTest |
| حقوق: | public |
| رقم الانضمام: | edsbas.D7F388E7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/mds.26238 |
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