title: Mosaic copy number variation in human neurons.
abstract: 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.
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McConnell
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lindberg
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Brennand
authors.forename: Julia C
authors.initials: JC
authors.lastname: Piper
authors.forename: Thierry
authors.initials: T
authors.lastname: Voet
authors.forename: Chris
authors.initials: C
authors.lastname: Cowing-Zitron
authors.forename: Svetlana
authors.initials: S
authors.lastname: Shumilina
authors.forename: Roger S
authors.initials: RS
authors.lastname: Lasken
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
authors.forename: Ira M
authors.initials: IM
authors.lastname: Hall
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000782:Aneuploidy; D056915:DNA Copy Number Variations; D005625:Frontal Lobe / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D008297:Male; D009030:Mosaicism; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D059010:Single-Cell Analysis