Neurons with Complex Karyotypes Are Rare in Aged Human Neocortex

被引：52

作者：

Chronister, William D. ^{[1
]}

Burbulis, Ian E. ^{[1
,11
]}

Wierman, Margaret B. ^{[1
]}

Wolpert, Matthew J. ^{[1
]}

Haakenson, Mark F. ^{[1
]}

Smith, Aiden C. B. ^{[1
]}

Kleinman, Joel E. ^{[6
,7
]}

Hyde, Thomas M. ^{[6
,7
,8
]}

Weinberger, Daniel R. ^{[6
,7
,8
,9
,10
]}

Bekiranov, Stefan ^{[1
,3
]}

McConnell, Michael J. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Virginia, Dept Biochem & Mol Genet, Sch Med, Charlottesville, VA 22908 USA

[2] Univ Virginia, Dept Neurosci, Sch Med, Charlottesville, VA 22908 USA

[3] Univ Virginia, Ctr Publ Hlth Genom, Sch Med, Charlottesville, VA 22908 USA

[4] Univ Virginia, Ctr Brain Immunol & Glia, Sch Med, Charlottesville, VA 22908 USA

[5] Univ Virginia, Child Hlth Res Ctr, Sch Med, Charlottesville, VA 22908 USA

[6] Johns Hopkins Univ, Lieber Inst Brain Dev, Sch Med, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Dept Psychiat, Sch Med, Baltimore, MD 21205 USA

[8] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21205 USA

[9] Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21205 USA

[10] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Sch Med, Baltimore, MD 21205 USA

[11] Univ San Sebastian, Escuela Med, Sede de la Patagonia, Puerto Montt, Chile

来源：

CELL REPORTS | 2019年 / 26卷 / 04期

关键词：

COPY-NUMBER VARIATION; SINGLE-CELL; L1; RETROTRANSPOSITION; STRUCTURAL VARIATION; SOMATIC MOSAICISM; MUTATIONS; EVOLUTION; GENOME; BRAIN; ANEUPLOIDY;

D O I：

10.1016/j.celrep.2018.12.107

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

A subset of human neocortical neurons harbors complex karyotypes wherein megabase-scale copy-number variants (CNVs) alter allelic diversity. Divergent levels of neurons with complex karyotypes (CNV neurons) are reported in different individuals, yet genome-wide and familial studies implicitly assume a single brain genome when assessing the genetic risk architecture of neurological disease. We assembled a brain CNV atlas using a robust computational approach applied to a new dataset (>800 neurons from 5 neurotypical individuals) and to published data from 10 additional neurotypical individuals. The atlas reveals that the frequency of neocortical neurons with complex karyotypes varies widely among individuals, but this variability is not readily accounted for by tissue quality or CNV detection approach. Rather, the age of the individual is anti-correlated with CNV neuron frequency. Fewer CNV neurons are observed in aged individuals than in young individuals.

引用

页码：825 / +

页数：18

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