Single-cell, genome-wide sequencing identifies clonal somatic copy-number variation in the human brain
Open accessAbstract
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.
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Single-cell sequencing has been used to measure the prevalence of large copy number variants in the brain.
“Single-cell sequencing has also been used to measure the prevalence of large copy number variants in the brain (McConnell, 2013; Cai, 2014).”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Cai, 2014
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References 33 · Cited by 318
- Authors
- Cai, X., Evrony, G. D., Lehmann, H. S., Elhosary, P. C., Mehta, B. K., Poduri, A., & Walsh, C. A.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Walsh, Christopher A.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 8
- Issue
- 5
- Pages
- 1280-1289
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4272008
- OpenAlex
- W2105970624
- Cited by
- 318
- References
- 33
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 9 · 2023: 10 · 2022: 48 · 2021: 29 · 2020: 23 · 2019: 35 · 2018: 33 · 2017: 34 · 2016: 40 · 2015: 29 · 2014: 4 · 2013: 1
- FWCI
- 23.36
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-02-03)
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5rc2mh089952-02)
- National Institute of Mental Health (1RC2MH089952, RC2-MH089952)
- National Institute of General Medical Sciences (T32GM007726, T32GM007753, T32GM007226)
- National Institute of Neurological Disorders and Stroke (R01NS035129, R01NS079277)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- somatic copy number variation, human brain, single-cell whole-genome sequencing, neurons, hemimegalencephaly, neuropsychiatric disorders, neurogenesis, lymphoblasts, brain development
- MeSH terms
- Brain, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 18, Humans, Lymphocytes, Neurons, Trisomy, Genome, Human, Sequence Analysis, DNA, DNA Copy Number Variations, Tetrasomy, Single-Cell Analysis, Hemimegalencephaly
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