Journal article
Common genetic variation drives molecular heterogeneity in human iPSCs
H Kilpinen, A Goncalves, A Leha, V Afzal, K Alasoo, S Ashford, S Bala, D Bensaddek, FP Casale, OJ Culley, P Danecek, A Faulconbridge, PW Harrison, A Kathuria, D McCarthy, SA McCarthy, R Meleckyte, Y Memari, N Moens, F Soares Show all
Nature | NATURE PORTFOLIO | Published : 2017
DOI: 10.1038/nature22403
Abstract
Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the va..
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Awarded by Biotechnology and Biological Sciences Research Council
Funding Acknowledgements
This work was funded with a strategic award from the Wellcome Trust and UK Medical Research Council (WT098503). We thank the staff in the Cellular Genetics and Phenotyping and Sequencing core facilities at the Wellcome Trust Sanger Institute. Work at the Wellcome Trust Sanger Institute was further supported by Wellcome Trust grant WT090851. H.K. is supported by a MRC eMedLab Medical Bioinformatics career development award from the UK Medical Research Council (MR/L016311/1). F.M.W. acknowledges financial support from the Department of Health via the NIHR Biomedical Research Centre award to Guy's & St Thomas' National Health Service Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. We acknowledge the participation of all NIHR Cambridge BioResource volunteers, and thank the NIHR Cambridge BioResource centre staff for their contribution. We thank the National Institute for Health Research and NHS Blood and Transplant. The NIHR/Wellcome Trust Cambridge Clinical Research Facility supported the volunteer recruitment. We acknowledge Life Science Technologies Corporation as the provider of Cytotune. We thank F.-J. Muller for insights regarding the PluriTest method, and the GTEx consortium for making raw data and intermediate results available.