Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium

Popp B, Krumbiegel M, Grosch J, Sommer A, Uebe S, Kohl Z, Ploetz S, Farrell M, Trautmann U, Kraus C, Ekici AB, Asadollahi R, Regensburger M, Guenther K, Rauch A, Edenhofer F, Winkler J, Winner B, Reis A (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 8

Journal Issue: 1

DOI: 10.1038/s41598-018-35506-0

Abstract

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.

Authors with CRIS profile

Bernt Popp Lehrstuhl für Humangenetik Janina Grosch Professur für Molekulare Neurologie Annika Sommer Klinisch-Molekularbiologisches Forschungszentrum Steffen Uebe Institute of Human Genetics Zacharias Kohl Department of Molecular Neurology Arif Bülent Ekici Lehrstuhl für Humangenetik Martin Regensburger Department of Neurology Jürgen Winkler Professur für Molekulare Neurologie Beate Winner Professur für Stammzell-Modelle seltener neuraler Erkrankungen André Wiesmann da Silva Reis Lehrstuhl für Humangenetik

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) University of Zurich / Universität Zürich (UZH) CH Switzerland (CH)

How to cite

APA:

Popp, B., Krumbiegel, M., Grosch, J., Sommer, A., Uebe, S., Kohl, Z.,... Reis, A. (2018). Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium. Scientific Reports, 8(1). https://dx.doi.org/10.1038/s41598-018-35506-0

MLA:

Popp, Bernt, et al. "Need for high-resolution Genetic Analysis in iPSC: Results and Lessons from the ForIPS Consortium." Scientific Reports 8.1 (2018).

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