title: Aneuploidy and confined chromosomal mosaicism in the developing human brain.
abstract: BACKGROUND
  Understanding the mechanisms underlying generation of neuronal variability and complexity remains the central challenge for neuroscience. Structural variation in the neuronal genome is likely to be one important mechanism for neuronal diversity and brain diseases. Large-scale genomic variations due to loss or gain of whole chromosomes (aneuploidy) have been described in cells of the normal and diseased human brain, which are generated from neural stem cells during intrauterine period of life. However, the incidence of aneuploidy in the developing human brain and its impact on the brain development and function are obscure.
  
  
  RESULTS
  To address genomic variation during development we surveyed aneuploidy/polyploidy in the human fetal tissues by advanced molecular-cytogenetic techniques at the single-cell level. Here we show that the human developing brain has mosaic nature, being composed of euploid and aneuploid neural cells. Studying over 600,000 neural cells, we have determined the average aneuploidy frequency as 1.25-1.45% per chromosome, with the overall percentage of aneuploidy tending to approach 30-35%. Furthermore, we found that mosaic aneuploidy can be exclusively confined to the brain.
  
  
  CONCLUSIONS
  Our data indicates aneuploidization to be an additional pathological mechanism for neuronal genome diversification. These findings highlight the involvement of aneuploidy in the human brain development and suggest an unexpected link between developmental chromosomal instability, intercellural/intertissular genome diversity and human brain diseases.
authors.affiliation: National Research Center of Mental Health, Russian Academy of Medical Sciences, Moscow, Russia; Institute of Pediatrics and Children Surgery, Roszdrav, Moscow, Russia. y_yurov@yahoo.com
authors.forename: Yuri B
authors.initials: YB
authors.lastname: Yurov
authors.forename: Ivan Y
authors.initials: IY
authors.lastname: Iourov
authors.forename: Svetlana G
authors.initials: SG
authors.lastname: Vorsanova
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Alexei D
authors.initials: AD
authors.lastname: Kolotii
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Kutsev
authors.forename: Franck
authors.initials: F
authors.lastname: Pellestor
authors.forename: Alfia K
authors.initials: AK
authors.lastname: Beresheva
authors.forename: Irina A
authors.initials: IA
authors.lastname: Demidova
authors.forename: Viktor S
authors.initials: VS
authors.lastname: Kravets
authors.forename: Viktor V
authors.initials: VV
authors.lastname: Monakhov
authors.forename: Ilia V
authors.initials: IV
authors.lastname: Soloviev
mesh_terms: D000782:Aneuploidy; D001921:Brain / Q000196:embryology* / Q000648:ultrastructure*; D002871:Chromosome Banding; D005333:Fetus; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009030:Mosaicism; D009473:Neuronal Plasticity