Mosaic aneuploidy with involvement of sex chromosomes Х and Y in cells of the brain in norm and mental pathology: search for genomic markers in schizophrenia

Experimental verification of the hypothesis about the possible involvement of the mosaic genome variations (mosaic aneuploidy) in the pathogenesis of a number of mental illnesses, including schizophrenia and autism: the level of mosaic genome variation in cells of the brain autopsy tissues in control and schizophrenia has been carried out. Autopsy brain tissues of 15 unaffected controls and 15 patients with schizophrenia were analyzed by molecular cytogenetic methods to determine the frequency of chromosomal mutations (the mosaic aneuploidy) in neural human cells. The original collection of chromosome-enumeration DNA probes to autosomes 1 and sex chromosomes X/Y was used for the interphase cytogenetic analysis of chromosomes in the cells of the brain. The frequency of low-level aneuploidy involving sex chromosomes X / Y in the control was 0.99 % (mean 0.8 %; 95 % confidence interval 0.60-1.38 %) and schizophrenia - 2.42 % (mean 2.4 %, 95 % CI 1,28-3,58 %), p=0.008 (Mann-Whitney U-test for independent groups). Thus, significant in-crease of aneuploidy frequency in the schizophrenia brain was detected. It was suggested that mosaic aneuploidy - a significant biological marker of genomic instability - may lead to genеtic imbalance and abnormal functional activity of neural cells and neural networks in schizophrenia.