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

被引：192

作者：

Cai, Xuyu ^{[1
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Evrony, Gilad D. ^{[1
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Lehmann, Hillel S. ^{[1
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Elhosary, Princess C. ^{[1
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Mehta, Bhaven K. ^{[1
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Poduri, Annapurna ^{[1
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Walsh, Christopher A. ^{[1
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机构：

[1] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA 02115 USA

[2] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[4] Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA 02138 USA

[5] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA

[6] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Boston, MA 02115 USA

来源：

CELL REPORTS | 2014年 / 8卷 / 05期

关键词：

RARE DE-NOVO; MUTATIONS; DISEASE; NUCLEOTIDE; DISORDERS; NEURONS; AUTISM; TUMOR;

D O I：

10.1016/j.celrep.2014.07.043

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 similar to 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.

引用

页码：1280 / 1289

页数：10