Un ADN par neurone , une découverte qui n'a pas fini de relancer notre compréhension du cerveau.
Dr Claude Jean PARIS

Mosaic Copy Number Variation in Human Neurons

1. Michael J. McConnell¹,²,⁷,⁸,⁹, 
2. Michael R. Lindberg⁷, 
3. Kristen J. Brennand¹,*, 
4. Julia C. Piper¹,²,†,
5. Thierry Voet³,⁴, 
6. Chris Cowing-Zitron¹, 
7. Svetlana Shumilina⁷, 
8. Roger S. Lasken⁵,⁶, 
9. Joris R. Vermeesch³,
10. Ira M. Hall⁷,⁹,‡, 
11. Fred H. Gage¹,‡

+Author Affiliations

1. ¹Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2. ²Crick-Jacobs Center for Theoretical and Computational Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
3. ³Center for Human Genetics, KU Leuven, 3000 Leuven, Belgium.
4. ⁴Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
5. ⁵J. Craig Venter Institute, San Diego, CA 92121, USA.
6. ⁶Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
7. ⁷Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
8. ⁸Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA 22908, USA.
9. ⁹Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.

+Author Notes

• ↵* Present address: Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
• ↵† Present address: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.

1. ↵‡Corresponding author. E-mail: irahall@virginia.edu (I.M.H.) and gage@salk.edu (F.H.G.)

• ABSTRACT
• EDITOR'S SUMMARY

We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC-derived neurons but not in matched neural progenitor cells. Single-cell sequencing of endogenous human frontal cortex neurons revealed that 13 to 41% of neurons have at least one megabase-scale de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic CNV is abundant in human neurons.

• Received for publication 19 July 2013.
• Accepted for publication 1 October 2013.