Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells (original) (raw)

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Primary accessions

Gene Expression Omnibus

Data deposits

The CNV array and sequencing data are available from Gene Expression Omnibus under accessions GSE41716 and GSE41563, and from https://ndarportal.nih.gov/ndarportal/NDARSTD289.

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Acknowledgements

We acknowledge support from the National Institutes of Health (NIH) and from the AL Williams Professorship fund and the Harris Professorship fund. We also acknowledge the Yale University Biomedical High Performance Computing Center and its support team (in particular, R. Bjornson and N. Carriero). We thank A. Klin for help with family recruitment. We thank M. V. Simonini for technical help, I.-H. Park for advice in the characterization of iPSC lines and the gift of the iPSC PGP1-1, and S. A. Duncan for the gift of the K3 iPSC line. We acknowledge the following grant support: NIMH MH089176 and MH087879, the Simons Foundation (SFARI 137055 F.V.) and the State of Connecticut, which funded the hiPSC generation and characterization; and NIH grant RR19895, which funded the instrumentation. We acknowledge the Yale Center for Clinical Investigation for clinical support in obtaining the biopsy specimens. We thank J. Overton for advice in carrying out DNA and RNA sequencing. Finally, we thank M. O’Huallachain and J. Li-Pook-Than for their advice on planning, carrying out and analysing the ddPCR experiments.

Author information

Author notes

1. Jessica Mariani, Dean Palejev, Ying Zhang, Michael Seamus Haney and Livia Tomasini: These authors contributed equally to this work.

Authors and Affiliations

1. Program in Neurodevelopment and Regeneration, Yale University, New Haven, 06520, Connecticut, USA
   Alexej Abyzov, Jessica Mariani, Dean Palejev, Ying Zhang, Livia Tomasini, Anthony F. Ferrandino, Lior A. Rosenberg Belmaker, Anna Szekely, Michael Wilson, Arif Kocabas, Nathaniel E. Calixto, Elena L. Grigorenko, Anita Huttner, Katarzyna Chawarska, Sherman Weissman, Alexander Eckehart Urban, Mark Gerstein & Flora M. Vaccarino
2. Program in Computation Biology and Bioinformatics, Yale University, New Haven, 06520, Connecticut, USA
   Alexej Abyzov, Michael Wilson & Mark Gerstein
3. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, 06520, Connecticut, USA
   Alexej Abyzov & Mark Gerstein
4. Child Study Center, Yale University, New Haven, 06520, Connecticut, USA
   Jessica Mariani, Dean Palejev, Livia Tomasini, Anthony F. Ferrandino, Lior A. Rosenberg Belmaker, Michael Wilson, Arif Kocabas, Nathaniel E. Calixto, Elena L. Grigorenko, Katarzyna Chawarska & Flora M. Vaccarino
5. Department of Genetics, Yale University, New Haven, 06520, Connecticut, USA
   Ying Zhang, Anna Szekely & Sherman Weissman
6. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 94305, California, USA
   Michael Seamus Haney & Alexander Eckehart Urban
7. Department of Genetics, School of Medicine, Stanford University, Stanford, 94305, California, USA
   Michael Seamus Haney & Alexander Eckehart Urban
8. Department of Neurology, Yale University, New Haven, 06520, Connecticut, USA
   Anna Szekely
9. Department of Psychology, Yale University, New Haven, 06520, Connecticut, USA
   Elena L. Grigorenko
10. Department of Epidemiology and Public Health, Yale University, New Haven, 06520, Connecticut, USA
    Elena L. Grigorenko
11. Department of Pathology, Yale University, New Haven, 06520, Connecticut, USA
    Anita Huttner
12. Department of Computer Science, Yale University, New Haven, 06520, Connecticut, USA
    Mark Gerstein
13. Department of Neurobiology, Yale University, New Haven, 06520, Connecticut, USA
    Flora M. Vaccarino

Authors

1. Alexej Abyzov
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2. Jessica Mariani
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3. Dean Palejev
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4. Ying Zhang
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5. Michael Seamus Haney
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6. Livia Tomasini
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7. Anthony F. Ferrandino
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8. Lior A. Rosenberg Belmaker
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9. Anna Szekely
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10. Michael Wilson
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11. Arif Kocabas
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12. Nathaniel E. Calixto
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13. Elena L. Grigorenko
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14. Anita Huttner
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15. Katarzyna Chawarska
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16. Sherman Weissman
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17. Alexander Eckehart Urban
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18. Mark Gerstein
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19. Flora M. Vaccarino
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Contributions

The authors contributed to this study at different levels, as described in the following. Study conception and design: F.M.V., A.A. and A.E.U. Family selection: E.L.G. Skin biopsy: A.S. Fibroblast culture: A.H. hiPSC generation and characterization: L.A.R.B., J.M. and L.T. Virus production: A.K. Microarrays data analysis: L.T. Neuronal differentiation: L.A.R.B., N.E.C. and J.M. Sequencing library preparation: L.A.R.B., J.M., L.T. and Y.Z. Processing and analysis of RNA-seq data: D.P. and A.A. Processing and analysis of DNAseq data: A.A. and M.W. qPCR validation: A.F.F. PCR validation: Y.Z. and A.A. aCGH hybridization and analysis: M.S.H. ddPCR experiments and analysis: M.S.H. and A.A. Human subjects: K.C. Coordination of analyses: F.M.V., S.W., A.E.U. and M.G. Display item preparation: A.A., F.M.V., L.T., D.P., J.M., N.E.C., Y.Z. and M.S.H. Manuscript writing: A.A., F.M.V. and A.E.U. The following authors contributed equally to the study: J.M., D.P., Y.Z., M.S.H. and L.T. All authors participated in discussion of results and manuscript editing.

Corresponding authors

Correspondence toAlexander Eckehart Urban, Mark Gerstein or Flora M. Vaccarino.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Text, Supplementary References, Supplementary Figures 1-57, Supplementary Tables 2, 5 and 6 and full legends for Supplementary Tables 1, 3 and 4 (see contents for details). (PDF 22730 kb)

Supplementary Table 1

This file contains the Gene expression microarray dataset - see Supplementary Information for full legend. (XLSX 2185 kb)

Supplementary Table 3

This file contains comprehensive information about all LM-CNV candidates - see Supplementary Information for full legend. (XLS 75 kb)

Supplementary Table 4

This file contains comprehensive information about LM-CNV candidates from aCGH - see Supplementary Information for full legend. (XLSX 12 kb)

Supplementary Data

This file shows the alignment of sequenced PCR bands to genomic regions with LM-CNVs. (TXT 197 kb)

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Abyzov, A., Mariani, J., Palejev, D. et al. Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells.Nature 492, 438–442 (2012). https://doi.org/10.1038/nature11629

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• Received: 16 January 2012
• Accepted: 28 September 2012
• Published: 18 November 2012
• Issue Date: 20 December 2012
• DOI: https://doi.org/10.1038/nature11629