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Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood
With several therapeutic approaches in development for Huntington's disease, there is a need for easily accessible biomarkers to monitor disease progression and therapy response. We performed next-generation sequencing-based transcriptome analysis of total RNA from peripheral blood of 91 mutati...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592077/ https://www.ncbi.nlm.nih.gov/pubmed/25626709 http://dx.doi.org/10.1038/ejhg.2014.281 |
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author | Mastrokolias, Anastasios Ariyurek, Yavuz Goeman, Jelle J van Duijn, Erik Roos, Raymund AC van der Mast, Roos C van Ommen, GertJan B den Dunnen, Johan T 't Hoen, Peter AC van Roon-Mom, Willeke MC |
author_facet | Mastrokolias, Anastasios Ariyurek, Yavuz Goeman, Jelle J van Duijn, Erik Roos, Raymund AC van der Mast, Roos C van Ommen, GertJan B den Dunnen, Johan T 't Hoen, Peter AC van Roon-Mom, Willeke MC |
author_sort | Mastrokolias, Anastasios |
collection | PubMed |
description | With several therapeutic approaches in development for Huntington's disease, there is a need for easily accessible biomarkers to monitor disease progression and therapy response. We performed next-generation sequencing-based transcriptome analysis of total RNA from peripheral blood of 91 mutation carriers (27 presymptomatic and, 64 symptomatic) and 33 controls. Transcriptome analysis by DeepSAGE identified 167 genes significantly associated with clinical total motor score in Huntington's disease patients. Relative to previous studies, this yielded novel genes and confirmed previously identified genes, such as H2AFY, an overlap in results that has proven difficult in the past. Pathway analysis showed enrichment of genes of the immune system and target genes of miRNAs, which are downregulated in Huntington's disease models. Using a highly parallelized microfluidics array chip (Fluidigm), we validated 12 of the top 20 significant genes in our discovery cohort and 7 in a second independent cohort. The five genes (PROK2, ZNF238, AQP9, CYSTM1 and ANXA3) that were validated independently in both cohorts present a candidate biomarker panel for stage determination and therapeutic readout in Huntington's disease. Finally we suggest a first empiric formula predicting total motor score from the expression levels of our biomarker panel. Our data support the view that peripheral blood is a useful source to identify biomarkers for Huntington's disease and monitor disease progression in future clinical trials. |
format | Online Article Text |
id | pubmed-4592077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45920772015-10-13 Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood Mastrokolias, Anastasios Ariyurek, Yavuz Goeman, Jelle J van Duijn, Erik Roos, Raymund AC van der Mast, Roos C van Ommen, GertJan B den Dunnen, Johan T 't Hoen, Peter AC van Roon-Mom, Willeke MC Eur J Hum Genet Article With several therapeutic approaches in development for Huntington's disease, there is a need for easily accessible biomarkers to monitor disease progression and therapy response. We performed next-generation sequencing-based transcriptome analysis of total RNA from peripheral blood of 91 mutation carriers (27 presymptomatic and, 64 symptomatic) and 33 controls. Transcriptome analysis by DeepSAGE identified 167 genes significantly associated with clinical total motor score in Huntington's disease patients. Relative to previous studies, this yielded novel genes and confirmed previously identified genes, such as H2AFY, an overlap in results that has proven difficult in the past. Pathway analysis showed enrichment of genes of the immune system and target genes of miRNAs, which are downregulated in Huntington's disease models. Using a highly parallelized microfluidics array chip (Fluidigm), we validated 12 of the top 20 significant genes in our discovery cohort and 7 in a second independent cohort. The five genes (PROK2, ZNF238, AQP9, CYSTM1 and ANXA3) that were validated independently in both cohorts present a candidate biomarker panel for stage determination and therapeutic readout in Huntington's disease. Finally we suggest a first empiric formula predicting total motor score from the expression levels of our biomarker panel. Our data support the view that peripheral blood is a useful source to identify biomarkers for Huntington's disease and monitor disease progression in future clinical trials. Nature Publishing Group 2015-10 2015-01-28 /pmc/articles/PMC4592077/ /pubmed/25626709 http://dx.doi.org/10.1038/ejhg.2014.281 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Article Mastrokolias, Anastasios Ariyurek, Yavuz Goeman, Jelle J van Duijn, Erik Roos, Raymund AC van der Mast, Roos C van Ommen, GertJan B den Dunnen, Johan T 't Hoen, Peter AC van Roon-Mom, Willeke MC Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood |
title | Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood |
title_full | Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood |
title_fullStr | Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood |
title_full_unstemmed | Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood |
title_short | Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood |
title_sort | huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592077/ https://www.ncbi.nlm.nih.gov/pubmed/25626709 http://dx.doi.org/10.1038/ejhg.2014.281 |
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