1. Neurons with Complex Karyotypes Are Rare in Aged Human Neocortex.
- Author
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Chronister WD, Burbulis IE, Wierman MB, Wolpert MJ, Haakenson MF, Smith ACB, Kleinman JE, Hyde TM, Weinberger DR, Bekiranov S, and McConnell MJ
- Subjects
- Aged, 80 and over, Female, Genome-Wide Association Study, Humans, Male, Aging genetics, Aging metabolism, Aging pathology, DNA Copy Number Variations, Genome, Human, Karyotype, Neocortex metabolism, Neocortex pathology, Neurons metabolism, Neurons pathology
- 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., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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