Constitutional aneuploidy in the normal human brain.
The mouse brain contains genetically distinct cells that differ with respect to chromosome number manifested as aneuploidy (Rehen et al., 2001); however, the relevance to humans is not known. Here, using double-label fluorescence in situ hybridization for the autosome chromosome 21 (chromosome 21 point probes combined with chromosome 21 "paint" probes), along with immunocytochemistry and cell sorting, we present evidence for chromosome gain and loss in the human brain. Chromosome 21 aneuploid cells constitute approximately 4% of the estimated one trillion cells in the human brain and include non-neuronal cells and postmitotic neurons identified by the neuronspecific nuclear protein marker. In comparison, human interphase lymphocytes present chromosome 21 aneuploidy rates of 0.6%. Together, these data demonstrate that human brain cells (both neurons and non-neuronal cells) can be aneuploid and that the resulting genetic mosaicism is a normal feature of the human CNS.
Rehen
Stevens K
SK
Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, California 92037, USA.
Yung
Yun C
YC
McCreight
Matthew P
MP
Kaushal
Dhruv
D
Yang
Amy H
AH
Almeida
Beatriz S V
BS
Kingsbury
Marcy A
MA
Cabral
Kátia M S
KM
McConnell
Michael J
MJ
Anliker
Brigitte
B
Fontanoz
Marisa
M
Chun
Jerold
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000166:cytology*; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007621:Karyotyping / Q000379:methods; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011180:Postmortem Changes
D010751:Phosphopyruvate Hydratase
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