The present study indicates that the aneuploidy level was in the range of 0.2 to 15.6% for different chromo­somes in the fetal brain cells. It means that the fetal neu­ronal cells to be characterized by increased frequency of non specific aneuploidy involved different chromosomes. Usually, fetal brain nuclei have one chromosome aberra­tion, involving any individual chromosome, tested in inter­phase FISH experiments. Only limited numbers of nuclei had two or more aberrations, involving different chromo­somes simultaneously. Approximately 95% neuronal cells could be considered as karyotypically normal, when we analyzed only one chromosome-specific DNA probe. However, mFISH analysis of several chromosomes in one FISH experiment, and application of a probe set for six different chromosomes, strongly indicated that the total number of chromosomally abnormal neuronal cells could be very high. For examples, we could estimate the total (cumulative) number of aberrant nuclei for six different chromosomes (1, 13/21, 18, X, Y) as 22%. We could propose that the number of aneuploidies in the fetal human brain cells, involving all 23 chromosome pairs, should be substantially higher. Therefore, our data strongly indicates that large-scale genomic (chromosomal) variations due to chromosomal complement instability in developing neu­ronal cells could take place and, therefore, this phenome­non can have a substantial effect on brain development.

There are no molecular-cytogenetic studies applying interphase FISH for the studies of the fetal human brain. Only the study of a model genetic object (mice) is avail­able at the present time. Direct FISH and spectral karyo­type analysis of neurons in the developing and adult ner­vous system of mouse embryonic cerebral cortical neuro­blast have been performed [2]. These approaches identify more than 30% of neuroblasts to be aneuploid. Therefore, it is possible that genomes in developing and adult mam­malian neurons can be different at the level of whole chro­mosomes.

There is only one indication, published in abstract form [6], that the fetal human brain could contain a large proportion of chromosomally abnormal cells. The results of the present study are in agreement with those data.

There are only limited numbers of molecular-cyto­genetic studies, utilizing interphase FISH for the studies of the adult human brain [12,13]. The use of the one-color FISH technique to examine the chromosomal complement of interphase nuclei in the adult human brain have demon­strated that a significant fraction of the hyppocampal py­ramidal and basal forebrain neurons in Alzheimer’s dis­ease have a fully of partially tetraploid chromosome com­plement. Yang et al. [12] propose that this imbalance in chromosome complement is the direct cause of neuronal loss in Alzheimer’s disease. A molecular-cytogenetic study, utilizing mFISH of post-mortem brain of schizo­phrenic patients, has been recently performed [13]. A statistically significant level of aneuploidy (up to 4% of neurons) was detected in the postmortem brain (prefrontal cortex, Brodmann’s area 10) of patients with schizophre­nia. The result indicated that a low-level of aneuploidy (or chromosomal mosaicism) could be involved in the patho­genesis of schizophrenia. Therefore, neuropsychiatric diseases might have a special interest for extended molecular-cytogenetic analysis as they could be associated with chromosomal and gene mutations involving in regula­tion of neuro developmental processes in the brain. It was proposed recently that the central nervous system, both during development and in adulthood, has genetic mosaic features: an euploid population intermixed with a smaller but genetically diverse aneuploid population. Such mosa­icism may have relevance to a variety of fields including stem cell biology, mammalian cloning, genomics, neuro­genetics and neuropsychiatric diseases. At the organism level, these permanent genomic changes might contribute to physiological and behavioral variations among individ­uals not accounted for by classical genetics. Therefore, even extremely low percentages of mosaic forms of aneu­ploidies really exist in the fetal and adult human brain; the presence of abnormal neuronal cells could significantly affect normal brain development and functions.

Nevertheless, the actual amount of chromosomally abnormal neuronal cells in the human brain is unknown. Taking into account the data that large-scale genomic variations due to chromosomal complement instability in developing neuronal cells are present and could have sub­stantial effect on normal brain development and functions, direct studies of chromosomal complements in the fetal and human brain should be continued.