@article{b36a73d753754a0488d9820583513eaf,
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.",
author = "Chronister, {William D.} and Burbulis, {Ian E.} and Wierman, {Margaret B.} and Wolpert, {Matthew J.} and Haakenson, {Mark F.} and Smith, {Aiden C.B.} and Kleinman, {Joel E.} and Hyde, {Thomas M.} and Weinberger, {Daniel R.} and Stefan Bekiranov and McConnell, {Michael J.}",
note = "Funding Information: We thank J. Lannigan and M. Solga (University of Virginia [UVA] fluorescence-activated cell sorting [FACS] core), Y. Bao (UVA genome analysis and technology core), and A. Koeppel (UVA bioinformatics core) for their contributed expertise. We thank P. Lansdorp (University of British Columbia) for prompt sharing of unpublished metadata, and F.H. Gage (Salk Institute) and J.V. Moran (University of Michigan) for critical feedback. Human tissue was obtained from the National Institute for Child Health and Human Development (NIH) Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore (contract HHSN2752009000011C, ref. no. N01-HD-9-011). Data are documented through the Brain Somatic Mosaicism Network Knowledge Portal ( synapse.org/BSMN ) and made available at the National Institute of Mental Health (NIMH) Data Archive. NIH funding to M.J.M. ( U01 MH106882 ), to D.R.W. ( U01 MH106893 ), and to M.J.M. and S.B. ( U01 MH106882-03S1 ) supported this work. I.E.B. received support from the McDonnell Foundation , and W.D.C. received support from NIH T32 GM008136-30 . Funding Information: We thank J. Lannigan and M. Solga (University of Virginia [UVA] fluorescence-activated cell sorting [FACS] core), Y. Bao (UVA genome analysis and technology core), and A. Koeppel (UVA bioinformatics core) for their contributed expertise. We thank P. Lansdorp (University of British Columbia) for prompt sharing of unpublished metadata, and F.H. Gage (Salk Institute) and J.V. Moran (University of Michigan) for critical feedback. Human tissue was obtained from the National Institute for Child Health and Human Development (NIH) Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore (contract HHSN2752009000011C, ref. no. N01-HD-9-011). Data are documented through the Brain Somatic Mosaicism Network Knowledge Portal (synapse.org/BSMN) and made available at the National Institute of Mental Health (NIMH) Data Archive. NIH funding to M.J.M. (U01 MH106882), to D.R.W. (U01 MH106893), and to M.J.M. and S.B. (U01 MH106882-03S1) supported this work. I.E.B. received support from the McDonnell Foundation, and W.D.C. received support from NIH T32 GM008136-30. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = jan,
day = "22",
doi = "10.1016/j.celrep.2018.12.107",
language = "English (US)",
volume = "26",
pages = "825--835.e7",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}