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Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium
Genetic integrity of induced pluripotent stem cells (iPSCs) is essential for their validity as disease models and for potential therapeutic use. We describe the comprehensive analysis in the ForIPS consortium: an iPSC collection from donors with neurological diseases and healthy controls. Characteri...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249203/ https://www.ncbi.nlm.nih.gov/pubmed/30464253 http://dx.doi.org/10.1038/s41598-018-35506-0 |
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author | Popp, Bernt Krumbiegel, Mandy Grosch, Janina Sommer, Annika Uebe, Steffen Kohl, Zacharias Plötz, Sonja Farrell, Michaela Trautmann, Udo Kraus, Cornelia Ekici, Arif B. Asadollahi, Reza Regensburger, Martin Günther, Katharina Rauch, Anita Edenhofer, Frank Winkler, Jürgen Winner, Beate Reis, André |
author_facet | Popp, Bernt Krumbiegel, Mandy Grosch, Janina Sommer, Annika Uebe, Steffen Kohl, Zacharias Plötz, Sonja Farrell, Michaela Trautmann, Udo Kraus, Cornelia Ekici, Arif B. Asadollahi, Reza Regensburger, Martin Günther, Katharina Rauch, Anita Edenhofer, Frank Winkler, Jürgen Winner, Beate Reis, André |
author_sort | Popp, Bernt |
collection | PubMed |
description | Genetic integrity of induced pluripotent stem cells (iPSCs) is essential for their validity as disease models and for potential therapeutic use. We describe the comprehensive analysis in the ForIPS consortium: an iPSC collection from donors with neurological diseases and healthy controls. Characterization included pluripotency confirmation, fingerprinting, conventional and molecular karyotyping in all lines. In the majority, somatic copy number variants (CNVs) were identified. A subset with available matched donor DNA was selected for comparative exome sequencing. We identified single nucleotide variants (SNVs) at different allelic frequencies in each clone with high variability in mutational load. Low frequencies of variants in parental fibroblasts highlight the importance of germline samples. Somatic variant number was independent from reprogramming, cell type and passage. Comparison with disease genes and prediction scores suggest biological relevance for some variants. We show that high-throughput sequencing has value beyond SNV detection and the requirement to individually evaluate each clone. |
format | Online Article Text |
id | pubmed-6249203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62492032018-11-28 Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium Popp, Bernt Krumbiegel, Mandy Grosch, Janina Sommer, Annika Uebe, Steffen Kohl, Zacharias Plötz, Sonja Farrell, Michaela Trautmann, Udo Kraus, Cornelia Ekici, Arif B. Asadollahi, Reza Regensburger, Martin Günther, Katharina Rauch, Anita Edenhofer, Frank Winkler, Jürgen Winner, Beate Reis, André Sci Rep Article Genetic integrity of induced pluripotent stem cells (iPSCs) is essential for their validity as disease models and for potential therapeutic use. We describe the comprehensive analysis in the ForIPS consortium: an iPSC collection from donors with neurological diseases and healthy controls. Characterization included pluripotency confirmation, fingerprinting, conventional and molecular karyotyping in all lines. In the majority, somatic copy number variants (CNVs) were identified. A subset with available matched donor DNA was selected for comparative exome sequencing. We identified single nucleotide variants (SNVs) at different allelic frequencies in each clone with high variability in mutational load. Low frequencies of variants in parental fibroblasts highlight the importance of germline samples. Somatic variant number was independent from reprogramming, cell type and passage. Comparison with disease genes and prediction scores suggest biological relevance for some variants. We show that high-throughput sequencing has value beyond SNV detection and the requirement to individually evaluate each clone. Nature Publishing Group UK 2018-11-21 /pmc/articles/PMC6249203/ /pubmed/30464253 http://dx.doi.org/10.1038/s41598-018-35506-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Popp, Bernt Krumbiegel, Mandy Grosch, Janina Sommer, Annika Uebe, Steffen Kohl, Zacharias Plötz, Sonja Farrell, Michaela Trautmann, Udo Kraus, Cornelia Ekici, Arif B. Asadollahi, Reza Regensburger, Martin Günther, Katharina Rauch, Anita Edenhofer, Frank Winkler, Jürgen Winner, Beate Reis, André Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium |
title | Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium |
title_full | Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium |
title_fullStr | Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium |
title_full_unstemmed | Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium |
title_short | Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium |
title_sort | need for high-resolution genetic analysis in ipsc: results and lessons from the forips consortium |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249203/ https://www.ncbi.nlm.nih.gov/pubmed/30464253 http://dx.doi.org/10.1038/s41598-018-35506-0 |
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