Interphase Chromosomes of the Human Brain: The Biological and Clinical Meaning of Neural Aneuploidy
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The human brain is generally assumed to be populated by cells that share identical genomes or diploid chromosome sets. However, interphase molecular cytogenetics has shown variable mosaic aneuploidy to be a new feature of brain cells. Interphase FISH analysis has estimated the amount of aneuploid cells as approximately 10 % (about 100 billion cells) in more than a trillion postmitotic neuronal and glial cells in the normal adult human brain. Paradoxically, aneuploidy appears to feature the mammalian brain despite representing a devastating condition in humans. Furthermore, neural aneuploidy rates vary during ontogeny. Aneuploidy rates are dramatically increased in early brain development, but decrease significantly in the postnatal period. Additionally, acquired aneuploidy affecting the brain is shown to be associated with neurodevelopmental and neurodegenerative disorders (i.e., autism, schizophrenia, ataxia-telangiectasia, Alzheimer’s disease). Furthermore, interphase molecular cytogenetics allows for the analysis of genome organization at the chromosomal level in brain cells, which is, unfortunately, beyond the scope of current neuroscience and genome research. Nonetheless, a number of pilot reports have determined analyzing interphase chromosome spatial organization in neuronal nuclei to be promising for genetics/genomics and cell biology of the human brain.
KeywordsRett Syndrome Aneuploid Cell Adult Human Brain Aneuploidy Rate Interphase Chromosome
The review is dedicated to the memory of Dr. Ilya V. Soloviev. We gratefully acknowledge the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD, USA, for providing samples of brain tissues. The authors are supported by DLR/BMBF (RUS 2011–2013) and RFBR grant 12-04-00215-а (Russian Federation, 2012–2014). Dr. IY Iourov is supported by the Grant of the President of the Russian Federation MD-4401.2013.7.
- Vorsanova SG, Yurov YB, Ulas VY, Demidova IA, Sharonin VO, Kolotii AD et al (2001) Cytogenetic and molecular-cytogenetic studies of Rett syndrome (RTT): a retrospective analysis of a Russian cohort of RTT patients (the investigation of 57 girls and three boys). Brain Dev 23:S196–S201PubMedCrossRefGoogle Scholar
- Vorsanova SG, Yurov IY, Demidova IA, Voinova-Ulas VY, Kravets VS, Solov’ev IV et al (2007) Variability in the heterochromatin regions of the chromosomes and chromosomal anomalies in children with autism: identification of genetic markers of autistic spectrum disorders. Neurosci Behav Physiol 37:553–558PubMedCrossRefGoogle Scholar
- Vorsanova SG, Voinova VY, Yurov IY, Kurinnaya OS, Demidova IA, Yurov YB (2010b) Cytogenetic, molecular-cytogenetic, and clinical-genealogical studies of the mothers of children with autism: a search for familial genetic markers for autistic disorders. Neurosci Behav Physiol 40(7):745–756PubMedCrossRefGoogle Scholar
- Weier HU, Munne S, Ferlatte C, Baumgartner A, Iourov IY, Racowsky C et al (2010) Aneuploidy—a necessary evil in human life. In: New trends in microscopy & immunohistochemistry (Histochemistry 2010), Proceedings of the histochemical 61st annual meeting. The Marine Biological Laboratory, Woods Hole, MA, pp 42–43Google Scholar
- Yurov YB, Vostrikov VM, Vorsanova SG, Monakhov VV, Iourov IY (2001) Multicolor fluorescent in situ hybridization on post-mortem brain in schizophrenia as an approach for identification of low-level chromosomal aneuploidy in neuropsychiatric diseases. Brain Dev 23:S186–S190PubMedCrossRefGoogle Scholar
- Yurov YB, Vorsanova SG, Kolotii AD, Liehr T, Iourov IY (2011b) Aneuploidy in the autistic brain: the first molecular cytogenetic study. Balkan J Med Genet 14(suppl 1):73Google Scholar
- Yurov YB, Vorsanova SG, Kolotii AD, Liehr T, Iourov IY (2012) Brain-specific X chromosome aneuploidy is likely to contribute to the pathogenesis of autism and can explain the unsolved paradox of male susceptibility. Eur J Hum Genet 20(suppl 1):109Google Scholar
- Zekanowski C, Wojda U (2009) Aneuploidy, chromosomal missegregation, and cell cycle reentry in Alzheimer’s disease. Acta Neurobiol Exp 6:232–253Google Scholar