Original article Multicolor fluorescent in situ hybridization on post-mortem brain in schizophrenia as an approach for identification of low-level chromosomal aneuploidy in neuropsychiatric diseases Yuri B. Yurov a,b, * , Viktor M. Vostrikov a , Svetlana G. Vorsanova b , Victor V. Monakhov a , Ivan Y. Iourov a a National Research Center of Mental Health, Russian Academy of Medical Sciences, Moscow 113152, Zagorodnoe sh. 2, Russia b Institute of Pediatrics and Children Surgery, Russian Ministry of Health, Moscow 127142, Russia Abstract Fluorescence in situ hybridization (FISH) of DNA-DNA or DNA-RNA using post-mortem brain samples is one approach to study low- level chromosomal aneuploidy and selective expression of specific genes in the brain of patients with neuropsychiatric diseases. We have performed a pilot molecular-cytogenetic analysis of post-mortem brain of schizophrenic patients. Multicolor FISH on two post-mortem brain samples of normal individuals and six schizophrenic individuals (area 10 of cortex) was applied. A set of DNA probes for FISH included: (i) centromeric alphoid DNA probes for chromosomes 7, 8, 13 and 21, 18, X and Y; (ii) classical satellite DNA probes for chromosomes 1 and 16; and (iii) region-specific DNA probes for chromosomes 13, 21 and 22. A statistically significant level of aneuploidy (up to 0.5–4% of neurons) involving chromosomes X and 18 was detected in two post-mortem brains of patients with schizophrenia. These results indicate that low-level chromosomal aneuploidy could be involved in the pathogenesis of schizophrenia. FISH could be applied to extended studies of chromosomal aneuploidy, abnormal patterns of chromosomal organization and functional gene expression in situ in the neurons of the brain in different psychiatric and neurodevelopmental diseases. Schizophrenia and Rett syndrome might be considered as psychiatric diseases of special interest for molecular-cytogenetic analysis as both of them could be associated with mutations in genes involving regulation of neurodevelopmental processes in the brain. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Molecular cytogenetics; Human brain; Schizophrenia; Rett syndrome 1. Introduction The organization of chromosomes and expression of genes in interphase nuclei of differentiated cells are only partially known. Highly differentiated cells from the central nervous system (CNS) have the advantage that neurons and most glial cells do not pass the cell division and do not replicate. Brain tissues could be the targets in many neuro- developmental and psychiatric diseases. Therefore, investi- gation of the organization and functioning of interphase chromosomes in the neurons of the brain could help in understanding genetic and epigenetic mechanisms underly- ing neuropsychiatric diseases. The in situ hybridization technique has often been applied in research of interphase chromosomes in various tissues. The Laura Manuelidis group performed pioneering inter- phase cytogenetic studies of tissues from the CNSs [1–3]. In human cerebellum, different patterns of interphase chro- mosome organization in functionally distinct cell types were observed [2]. This group also described a repositioning of chromosome X in neurons of epileptic foci [4]. They suggested that an altered nuclear pattern involving chromo- some X might create the genetic memory for seizure activ- ity. This report firstly illustrates the possible pathological importance of abnormal patterns of chromosomal organiza- tion in interphase nuclei of highly differentiated cells in the brain. Interphase cytogenetics revealed somatic pairing of chro- mosome 1 and 17 centromeric heterochromatin, but not for chromosomes 6, 10, 11 and 18 in normal human brain tissues at autopsy [5,6]. The authors suggested that the loca- lization of chromosomes in interphase nuclei is dependent on the functional state of the cells. From the data of inter- phase cytogenetics, it seems worthwhile to focus on the analysis of chromosomal organization in different cell Brain & Development 23 (2001) S186–S190 0387-7604/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S0387-7604(01)00363-1 www.elsevier.com/locate/braindev * Corresponding author. National Research Center of Mental Health, RAMS, Moscow 113152, Zagorodnoe sh. 2, Russia. Fax: 17-095-952- 89-40. E-mail addresses: yurov@rcmh.msk.ru (Y.B. Yurov), yurov@pediatr.mtu-net.ru (Y.B. Yurov).