title: Constitutional aneuploidy in the normal human brain.
abstract: 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.
authors.affiliation: Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Stevens K
authors.initials: SK
authors.lastname: Rehen
authors.forename: Yun C
authors.initials: YC
authors.lastname: Yung
authors.forename: Matthew P
authors.initials: MP
authors.lastname: McCreight
authors.forename: Dhruv
authors.initials: D
authors.lastname: Kaushal
authors.forename: Amy H
authors.initials: AH
authors.lastname: Yang
authors.forename: Beatriz S V
authors.initials: BS
authors.lastname: Almeida
authors.forename: Marcy A
authors.initials: MA
authors.lastname: Kingsbury
authors.forename: Kátia M S
authors.initials: KM
authors.lastname: Cabral
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McConnell
authors.forename: Brigitte
authors.initials: B
authors.lastname: Anliker
authors.forename: Marisa
authors.initials: M
authors.lastname: Fontanoz
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
mesh_terms: 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
chemical_list: D010751:Phosphopyruvate Hydratase
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