TY - JOUR
T1 - Mosaic copy number variation in human neurons
AU - McConnell, Michael J.
AU - Lindberg, Michael R.
AU - Brennand, Kristen J.
AU - Piper, Julia C.
AU - Voet, Thierry
AU - Cowing-Zitron, Chris
AU - Shumilina, Svetlana
AU - Lasken, Roger S.
AU - Vermeesch, Joris R.
AU - Hall, Ira M.
AU - Gage, Fred H.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84887315590&partnerID=8YFLogxK
U2 - 10.1126/science.1243472
DO - 10.1126/science.1243472
M3 - Article
C2 - 24179226
AN - SCOPUS:84887315590
SN - 0036-8075
VL - 342
SP - 632
EP - 637
JO - Science
JF - Science
IS - 6158
ER -