Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain

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...

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Main Authors:	Cai, Xuyu, Evrony, Gilad D., Lehmann, Hillel S., Elhosary, Princess C., Mehta, Bhaven K., Poduri, Annapurna, Walsh, Christopher A.
Format:	Online
Language:	English
Published:	2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272008/

id	pubmed-4272008
recordtype	oai_dc
spelling	pubmed-42720082014-12-19 Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain Cai, Xuyu Evrony, Gilad D. Lehmann, Hillel S. Elhosary, Princess C. Mehta, Bhaven K. Poduri, Annapurna Walsh, Christopher A. Article 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. 2014-08-21 2014-09-11 /pmc/articles/PMC4272008/ /pubmed/25159146 http://dx.doi.org/10.1016/j.celrep.2014.07.043 Text en © 2014 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Cai, Xuyu Evrony, Gilad D. Lehmann, Hillel S. Elhosary, Princess C. Mehta, Bhaven K. Poduri, Annapurna Walsh, Christopher A.
spellingShingle	Cai, Xuyu Evrony, Gilad D. Lehmann, Hillel S. Elhosary, Princess C. Mehta, Bhaven K. Poduri, Annapurna Walsh, Christopher A. Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain
author_facet	Cai, Xuyu Evrony, Gilad D. Lehmann, Hillel S. Elhosary, Princess C. Mehta, Bhaven K. Poduri, Annapurna Walsh, Christopher A.
author_sort	Cai, Xuyu
title	Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain
title_short	Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain
title_full	Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain
title_fullStr	Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain
title_full_unstemmed	Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain
title_sort	single-cell, genome-wide sequencing identifies clonal somatic copy-number variation in the human brain
description	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.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272008/
_version_	1613169225257451520

Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain

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