Open AccessNeurons with Complex Karyotypes Are Rare in Aged Human Neocortex
Author(s) -
William D. Chronister,
Ian 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
Publication year - 2019
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2018.12.107
Subject(s) - neocortex , neurotypical , biology , copy number variation , karyotype , neuroscience , genetics , genome , evolutionary biology , chromosome , psychology , gene , autism , autism spectrum disorder , developmental psychology
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.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom