Mosaic copy number variation in human neurons.

Bibliographic Collection: 
APE, CARTA-Inspired Publication
Publication Type: Journal Article
Authors: McConnell, Michael J; Lindberg, Michael R; Brennand, Kristen J; Piper, Julia C; Voet, Thierry; Cowing-Zitron, Chris; Shumilina, Svetlana; Lasken, Roger S; Vermeesch, Joris R; Hall, Ira M; Gage, Fred H
Year of Publication: 2013
Journal: Science
Volume: 342
Issue: 6158
Pagination: 632-7
Date Published: 2013 Nov 1
Publication Language: eng
ISSN: 1095-9203
Keywords: Aneuploidy, DNA Copy Number Variations, Frontal Lobe, Humans, Induced Pluripotent Stem Cells, Male, Mosaicism, Neural Stem Cells, Neurogenesis, Neurons, Sequence Analysis, DNA, Sequence Deletion, Single-Cell Analysis

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.

DOI: 10.1126/science.1243472
Alternate Journal: Science