Mosaic Copy Number Variation in Human Neurons

• Published in: Science (American Association for the Advancement of Science) Vol. 342; no. 6158; pp. 632 - 637
• Main Authors: McConnell, Michael J., Lindberg, Michael R., Brennend, Kristen J., Piper, Julia C., Voet, Thierry, Cowing-Zitron, Chris, Shumilina, Svetlana, Lasken, Roger S., Vermeesch, Joris R., Hall, Ira M., Gage, Fred H.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 01.11.2013; The American Association for the Advancement of Science
• Subjects: Aneuploidy; antibody diversity; Biological and medical sciences; Cell differentiation; Cell lines; Cells; Chromosomes; DNA Copy Number Variations; Fibroblasts; frontal lobe; Frontal Lobe - cytology; Fundamental and applied biological sciences. Psychology; genome; Genomes; Genomics; Humans; Immune system; Individualized Instruction; Induced Pluripotent Stem Cells - cytology; Male; Mosaicism; mutation; Neural Stem Cells - cytology; Neurogenesis; Neurons; Neurons - cytology; Sequence Analysis, DNA; Sequence Deletion; Sequencing; Single-Cell Analysis; Somatic cells; Stem cells; Vertebrates: nervous system and sense organs; Human; Cell line; Neuron; Stem cell; DNA; Central nervous system; Precursor cell; Postmortem; Frontal cortex; Fibroblast; Encephalon
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1243472

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 4 1% of neurons have at least one mega base-sea le 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.