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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doaj-6f741291a24e4939a5ac4204f25b68de2020-11-24T21:15:54ZengElsevierCell Reports2211-12472014-09-01851280128910.1016/j.celrep.2014.07.043Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human BrainXuyu Cai0Gilad D. Evrony1Hillel S. Lehmann2Princess C. Elhosary3Bhaven K. Mehta4Annapurna Poduri5Christopher A. Walsh6Division of Genetics and Genomics, Manton Center for Orphan Disease Research and Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 02115, USADivision of Genetics and Genomics, Manton Center for Orphan Disease Research and Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 02115, USADivision of Genetics and Genomics, Manton Center for Orphan Disease Research and Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 02115, USADivision of Genetics and Genomics, Manton Center for Orphan Disease Research and Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 02115, USADivision of Genetics and Genomics, Manton Center for Orphan Disease Research and Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 02115, USADivision of Genetics and Genomics, Manton Center for Orphan Disease Research and Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 02115, USADivision of Genetics and Genomics, Manton Center for Orphan Disease Research and Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 02115, USADe 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.http://www.sciencedirect.com/science/article/pii/S2211124714006275 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuyu Cai Gilad D. Evrony Hillel S. Lehmann Princess C. Elhosary Bhaven K. Mehta Annapurna Poduri Christopher A. Walsh |
spellingShingle |
Xuyu Cai Gilad D. Evrony Hillel S. Lehmann Princess C. Elhosary Bhaven K. Mehta Annapurna Poduri Christopher A. Walsh Single-Cell, Genome-wide Sequencing Identifies Clonal Somatic Copy-Number Variation in the Human Brain Cell Reports |
author_facet |
Xuyu Cai Gilad D. Evrony Hillel S. Lehmann Princess C. Elhosary Bhaven K. Mehta Annapurna Poduri Christopher A. Walsh |
author_sort |
Xuyu Cai |
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 |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2014-09-01 |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124714006275 |
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