PMID- 17889509
OWN - NLM
STAT- MEDLINE
DCOM- 20080331
LR  - 20220321
IS  - 0920-9964 (Print)
IS  - 0920-9964 (Linking)
VI  - 98
IP  - 1-3
DP  - 2008 Jan
TI  - The schizophrenia brain exhibits low-level aneuploidy involving chromosome 1.
PG  - 139-47
AB  - OBJECTIVE: Genetic instability manifested as loss or gain of whole chromosomes 
      (aneuploidy) is a newly described feature of the human brain. Aneuploidy in the 
      brain was hypothesized to be involved in schizophrenia pathogenesis. To gain 
      further insights into the relationship between aneuploidy in the brain and 
      schizophrenia pathogenesis, a molecular-cytogenetic study of chromosome 1 
      aneuploidy was performed. METHODS: Interphase multiprobe fluorescence in situ 
      hybridization (FISH) with quantitative FISH (QFISH) and interphase 
      chromosome-specific multicolor banding (ICS-MCB) were used to define aneuploidy 
      rate in 12 unaffected and 12 schizophrenia brains. RESULTS: In the unaffected 
      brain (n=12; 22,794 cells analyzed), average frequencies of stochastic chromosome 
      1 loss and gain were 0.3% (95%CI 0.2-0.4%) and 0.3% (95%CI 0.2-0.4%), 
      respectively. The threshold level for stochastic chromosome gain and loss (the 
      mean+3SD) in the normal brain was 0.7%. Average rate of aneuploidy in the 
      schizophrenia brain (n=12; 28,482 cells analyzed) was 0.9% (95%CI 0.3-1.5%) for 
      chromosome 1 loss and 0.9% (95%CI 0.2-1.7%) for chromosome 1 gain. Significantly 
      increased level of mosaic aneuploidy involving chromosome 1 was revealed in two 
      schizophrenia brains (3.6% and 4.7% of cells with chromosome 1 loss and gain, 
      respectively). Stochastic aneuploidy rate for chromosome 1 in the schizophrenia 
      brain without two outliers (n=10) reached 0.6% (95%CI 0.3-0.9%) for loss and 0.5% 
      (0.2-0.9%) for gain and was higher than in controls (P=0.005 and P=0.001, 
      respectively). CONCLUSIONS: Our findings support the hypothesis suggesting that 
      subtle genomic imbalances manifesting as low-level mosaic aneuploidy may 
      contribute to schizophrenia pathogenesis.
FAU - Yurov, Yuri B
AU  - Yurov YB
AD  - National Research Center of Mental Health, Russian Academy of Medical Sciences, 
      Moscow 119152, Russian Federation. y_yurov@yahoo.com
FAU - Iourov, Ivan Y
AU  - Iourov IY
FAU - Vorsanova, Svetlana G
AU  - Vorsanova SG
FAU - Demidova, Irina A
AU  - Demidova IA
FAU - Kravetz, Viktor S
AU  - Kravetz VS
FAU - Beresheva, Alphia K
AU  - Beresheva AK
FAU - Kolotii, Alexei D
AU  - Kolotii AD
FAU - Monakchov, Viktor V
AU  - Monakchov VV
FAU - Uranova, Natalia A
AU  - Uranova NA
FAU - Vostrikov, Viktor M
AU  - Vostrikov VM
FAU - Soloviev, Ilia V
AU  - Soloviev IV
FAU - Liehr, Thomas
AU  - Liehr T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070921
PL  - Netherlands
TA  - Schizophr Res
JT  - Schizophrenia research
JID - 8804207
SB  - IM
MH  - Age of Onset
MH  - *Aneuploidy
MH  - Brain/*metabolism
MH  - Chromosomes, Human, Pair 1/*genetics/metabolism
MH  - Control Groups
MH  - Female
MH  - Genomic Instability/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Male
MH  - Middle Aged
MH  - *Mosaicism
MH  - Schizophrenia/*genetics/*metabolism
MH  - Stochastic Processes
EDAT- 2007/09/25 09:00
MHDA- 2008/04/01 09:00
CRDT- 2007/09/25 09:00
PHST- 2007/05/23 00:00 [received]
PHST- 2007/07/26 00:00 [revised]
PHST- 2007/07/27 00:00 [accepted]
PHST- 2007/09/25 09:00 [pubmed]
PHST- 2008/04/01 09:00 [medline]
PHST- 2007/09/25 09:00 [entrez]
AID - S0920-9964(07)00329-5 [pii]
AID - 10.1016/j.schres.2007.07.035 [doi]
PST - ppublish
SO  - Schizophr Res. 2008 Jan;98(1-3):139-47. doi: 10.1016/j.schres.2007.07.035. Epub 
      2007 Sep 21.