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Cell Rep DOI:10.1016/j.celrep.2014.07.043

Single-cell, genome-wide sequencing identifies clonal somatic copy-number variation in the human brain.

Publication TypeJournal Article
Year of Publication2014
AuthorsCai, X, Evrony, GD, Lehmann, HS, Elhosary, PC, Mehta, BK, Poduri, A, Walsh, CA
JournalCell Rep
Date Published2014 Sep 11
KeywordsBrain, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 18, DNA Copy Number Variations, Genome, Human, Hemimegalencephaly, Humans, Lymphocytes, Neurons, Sequence Analysis, DNA, Single-Cell Analysis, Tetrasomy, Trisomy

De novo copy-number variants (CNVs) can cause neuropsychiatric disease, but the degree to which they occur somatically, and during development, is unknown. Single-cell whole-genome sequencing (WGS) in >200 single cells, including >160 neurons from three normal and two pathological human brains, sensitively identified germline trisomy of chromosome 18 but found most (≥ 95%) neurons in normal brain tissue to be euploid. Analysis of a patient with hemimegalencephaly (HMG) due to a somatic CNV of chromosome 1q found unexpected tetrasomy 1q in ∼ 20% of neurons, suggesting that CNVs in a minority of cells can cause widespread brain dysfunction. Single-cell analysis identified large (>1 Mb) clonal CNVs in lymphoblasts and in single neurons from normal human brain tissue, suggesting that some CNVs occur during neurogenesis. Many neurons contained one or more large candidate private CNVs, including one at chromosome 15q13.2-13.3, a site of duplication in neuropsychiatric conditions. Large private and clonal somatic CNVs occur in normal and diseased human brains.


Alternate JournalCell Rep
PubMed ID25159146
PubMed Central IDPMC4272008
Grant ListRC2 MH089952 / MH / NIMH NIH HHS / United States
R01NS079277 / NS / NINDS NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
R01NS035129 / NS / NINDS NIH HHS / United States
R01 NS079277 / NS / NINDS NIH HHS / United States
1RC2MH089952 / MH / NIMH NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
R01 NS035129 / NS / NINDS NIH HHS / United States
T32GM007753 / GM / NIGMS NIH HHS / United States
T32GM007726 / GM / NIGMS NIH HHS / United States