Neurons with Complex Karyotypes Are Rare in Aged Human Neocortex

William D. Chronister; Ian E. Burbulis; Margaret B. Wierman; Matthew J. Wolpert; Mark F. Haakenson; Aiden C.B. Smith; Joel E. Kleinman; Thomas M. Hyde; Daniel R. Weinberger; Stefan Bekiranov; Michael J. McConnell

doi:10.1016/j.celrep.2018.12.107

Neurons with Complex Karyotypes Are Rare in Aged Human Neocortex

William D. Chronister, Ian E. Burbulis, Margaret B. Wierman, Matthew J. Wolpert, Mark F. Haakenson, Aiden C.B. Smith, Joel E. Kleinman, Thomas M. Hyde, Daniel R. Weinberger, Stefan Bekiranov, Michael J. McConnell

School of Medicine

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	825-835.e7
Journal	Cell Reports
Volume	26
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2018.12.107
State	Published - Jan 22 2019

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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title = "Neurons with Complex Karyotypes Are Rare in Aged Human Neocortex",

abstract = "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.",

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AU - Wolpert, Matthew J.

AU - Haakenson, Mark F.

AU - Smith, Aiden C.B.

AU - Kleinman, Joel E.

AU - Hyde, Thomas M.

AU - Weinberger, Daniel R.

AU - Bekiranov, Stefan

AU - McConnell, Michael J.

PY - 2019/1/22

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N2 - 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.

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Neurons with Complex Karyotypes Are Rare in Aged Human Neocortex

Abstract

ASJC Scopus subject areas

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