RT Journal Article
SR Electronic
T1 CNV Neurons Are Rare in Aged Human Neocortex
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 303404
DO 10.1101/303404
A1 William D. Chronister
A1 Margaret B. Wierman
A1 Ian E. Burbulis
A1 Matthew J. Wolpert
A1 Mark F. Haakenson
A1 Joel E. Kleinman
A1 Thomas Hyde
A1 Daniel R. Weinberger
A1 Stefan Bekiranov
A1 Michael J. McConnell
YR 2018
UL http://biorxiv.org/content/early/2018/04/21/303404.abstract
AB Megabase-scale somatic copy number variants (CNVs) alter allelic diversity in a subset of human neocortical neurons. Reported frequencies of CNV neurons range from ∼5% of neurons in some individuals to greater than 30% in other individuals. Genome-wide and familial studies implicitly assume a constant brain genome when assessing the genetic risk architecture of neurological disease, thus it is critical to determine whether divergent reports of CNV neuron frequency reflect normal individual variation or technical differences between approaches. We generated a new dataset of over 800 human neurons from 5 neurotypical individuals and developed a computational approach that measures single cell library quality based on Bayesian Information Criterion and identifies integer-like variant segments from population-level statistics. A brain CNV atlas was assembled using our new dataset and published data from 10 additional neurotypical individuals. This atlas reveals that the frequency of neocortical CNV neurons varies widely among individuals, but that 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 young individuals.