Advertisement

Interphase Chromosomes of the Human Brain: The Biological and Clinical Meaning of Neural Aneuploidy

Chapter

Abstract

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.

Keywords

Rett Syndrome Aneuploid Cell Adult Human Brain Aneuploidy Rate Interphase Chromosome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

 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.

References

  1. Arendt T (2012) Cell cycle activation and aneuploid neurons in Alzheimer’s disease. Mol Neurobiol 46(1):125–135PubMedCrossRefGoogle Scholar
  2. Arendt T, Mosch B, Morawski M (2009) Neuronal aneuploidy in health and disease: a cytomic approach to understand the molecular individuality of neurons. Int J Mol Sci 10:1609–1627PubMedCrossRefGoogle Scholar
  3. Arendt T, Brückner MK, Mosch B, Lösche A (2010) Selective cell death of hyperploid neurons in Alzheimer’s disease. Am J Pathol 177:15–20PubMedCrossRefGoogle Scholar
  4. Arnoldus EP, Peters AC, Bots GT, Raap AK, van der Ploeg M (1989) Somatic pairing of chromosome 1 centromeres in interphase nuclei of human cerebellum. Hum Genet 83(3):231–234PubMedCrossRefGoogle Scholar
  5. Arnoldus EP, Noordermeer IA, Peters AC, Raap AK, Van der Ploeg M (1991) Interphase cytogenetics reveals somatic pairing of chromosome 17 centromeres in normal human brain tissue, but no trisomy 7 or sex-chromosome loss. Cytogenet Cell Genet 56(3–4):214–216PubMedCrossRefGoogle Scholar
  6. Arnoldus EP, Wolters LB, Voormolen JH, van Duinen SG, Raap AK, van der Ploeg M, Peters AC (1992) Interphase cytogenetics: a new tool for the study of genetic changes in brain tumors. J Neurosurg 76(6):997–1003PubMedCrossRefGoogle Scholar
  7. Astolfi PA, Salamini F, Sgaramella V (2010) Are we genomic mosaics? Variations of the genome of somatic cells can contribute to diversify our phenotypes. Curr Genomics 11:379–386PubMedCrossRefGoogle Scholar
  8. Betancur C (2011) Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res 1380:42–77PubMedCrossRefGoogle Scholar
  9. Boeras DI, Granic A, Padmanabhan J, Crespo NC, Rojiani AM, Potter H (2008) Alzheimer’s presenilin 1 causes chromosome missegregation and aneuploidy. Neurobiol Aging 29:319–328PubMedCrossRefGoogle Scholar
  10. Borysov SI, Granic A, Padmanabhan J, Walczak CE, Potter H (2011) Alzheimer Aβ disrupts the mitotic spindle and directly inhibits mitotic microtubule motors. Cell Cycle 10:1397–1410PubMedCrossRefGoogle Scholar
  11. Castermans D, Willquet V, Steyert J, Van de Ven W, Fryns JP, Devriendt K (2004) Chromosomal anomalies in individuals with autism: a strategy towards the identification of genes involved in autism. Autism 8:141–161PubMedCrossRefGoogle Scholar
  12. Chen J, Cohen ML, Lerner AJ, Yang Y, Herrup K (2010) DNA damage and cell cycle events implicate cerebellar dentate nucleus neurons as targets of Alzheimer’s disease. Mol Neurodegener 5:60PubMedCrossRefGoogle Scholar
  13. Chun J, Westra JW, Bushman D (2011) Reply to Iourov et al. Neurodegen Dis 8:38–40CrossRefGoogle Scholar
  14. Dastidar SG, Bardai FH, Ma C, Price V, Rawat V, Verma P, Narayanan V, D’Mello SR (2012) Isoform-specific toxicity of Mecp2 in postmitotic neurons: suppression of neurotoxicity by FoxG1. J Neurosci 32(8):2846–2855PubMedCrossRefGoogle Scholar
  15. de Moraes LS, Khayat AS, de Lima PD, Lima EM, Pinto GR, Leal MF, de Arruda Cardoso Smith M, Burbano RR (2010) Chromosome X aneuploidy in Brazilian schizophrenic patients. In Vivo 24:281–286PubMedGoogle Scholar
  16. DeLisi LE, Friedrich U, Wahlstrom J, Boccio-Smith A, Eklund K, Crow TJ (1994) Schizophrenia and sex chromosome anomalies. Schizophr Bull 20(3):495–505PubMedCrossRefGoogle Scholar
  17. DeLisi LE, Maurizio AM, Svetina C, Ardekani B, Szulc K, Nierenberg J et al (2005) Klinefelter’s syndrome (XXY) as a genetic model for psychotic disorders. Am J Med Genet B Neuropsychiatr Genet 135B(1):15–23PubMedCrossRefGoogle Scholar
  18. Dierssen M, Herault Y, Estivill X (2009) Aneuploidy: from a physiological mechanism of variance to Down syndrome. Physiol Rev 89:887–920PubMedCrossRefGoogle Scholar
  19. Duesberg P, Li R, Fabarius A, Hehlmann R (2005) The chromosomal basis of cancer. Cell Oncol 27(5-6):293–318PubMedGoogle Scholar
  20. Faggioli F, Vijg J, Montagna C (2011) Chromosomal aneuploidy in the aging brain. Mech Ageing Dev 132(8–9):429–436PubMedCrossRefGoogle Scholar
  21. Faggioli F, Wang T, Vijg J, Montagna C (2012) Chromosome-specific accumulation of aneuploidy in the aging mouse brain. Hum Mol Genet 21(24):5246–5253. doi: 10.1093/hmg/dds375 PubMedCrossRefGoogle Scholar
  22. Fischer HG, Morawski M, Brückner MK, Mittag A, Tarnok A, Arendt T (2012) Changes in neuronal DNA content variation in the human brain during aging. Aging Cell 11(4):628–633PubMedCrossRefGoogle Scholar
  23. Geller LN, Potter H (1999) Chromosome missegregation and trisomy 21 mosaicism in Alzheimer’s disease. Neurobiol Dis 6:167–179PubMedCrossRefGoogle Scholar
  24. Granic A, Padmanabhan J, Norden M, Potter H (2010) Alzheimer Abeta peptide induces chromosome mis-segregation and aneuploidy, including trisomy 21: requirement for au and APP. Mol Biol Cell 21(4):511–520PubMedCrossRefGoogle Scholar
  25. Hassold T, Hall H, Hunt P (2007) The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet 16:R203–R208PubMedCrossRefGoogle Scholar
  26. Herrup K, Yang Y (2007) Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? Nat Rev Neurosci 8:368–378PubMedCrossRefGoogle Scholar
  27. Heston LL, Mastri AR (1977) The genetics of Alzheimer’s disease: associations with hematologic malignancy and Down’s syndrome. Arch Gen Psychiatry 34(8):976–981PubMedCrossRefGoogle Scholar
  28. Hultén MA, Patel SD, Tankimanova M, Westgren M, Papadogiannakis N, Jonsson AM, Iwarsson E (2008) On the origin of trisomy 21 Down syndrome. Mol Cytogenet 1:21PubMedCrossRefGoogle Scholar
  29. Hultén MA, Jonasson J, Nordgren A, Iwarsson E (2010) Germinal and somatic trisomy 21 mosaicism: how common is it, what are the implications for individual carriers and how does it come about? Curr Genomics 11:409–419PubMedCrossRefGoogle Scholar
  30. Hultén MA, Jonasson J, Iwarsson E, Uppal P, Vorsanova SG, Yurov YB, Iourov IY (2013) Trisomy 21 mosaicism: we may all have a touch of Down syndrome. Cytogenet Genome Res. DOI:10.1159/000346028PubMedCrossRefGoogle Scholar
  31. Iourov IY, Soloviev IV, Vorsanova SG, Monakhov VV, Yurov YB (2005) An approach for quantitative assessment of fluorescence in situ hybridization (FISH) signals for applied human molecular cytogenetics. J Histochem Cytochem 53:401–408PubMedCrossRefGoogle Scholar
  32. Iourov IY, Liehr T, Vorsanova SG, Kolotii AD, Yurov YB (2006a) Visualization of interphase chromosomes in postmitotic cells of the human brain by multicolour banding (MCB). Chromosome Res 14:223–229PubMedCrossRefGoogle Scholar
  33. Iourov IY, Vorsanova SG, Pellestor F, Yurov YB (2006b) Brain tissue preparations for chromosomal PRINS labeling. Methods Mol Biol 334:123–132PubMedGoogle Scholar
  34. Iourov IY, Vorsanova SG, Yurov YB (2006c) Chromosomal variation in mammalian neuronal cells: known facts and attractive hypotheses. Int Rev Cytol 249:143–191PubMedCrossRefGoogle Scholar
  35. Iourov IY, Vorsanova SG, Yurov YB (2006d) Intercellular genomic (chromosomal) variations resulting in somatic mosaicism: mechanisms and consequences. Curr Genomics 7:435–446CrossRefGoogle Scholar
  36. Iourov IY, Liehr T, Vorsanova SG, Yurov YB (2007a) Interphase chromosome-specific multicolor banding (ICS-MCB): a new tool for analysis of interphase chromosomes in their integrity. Biomol Eng 24:415–417PubMedCrossRefGoogle Scholar
  37. Iourov IY, Vorsanova SG, Yurov YB (2007b) Ataxia telangiectasia paradox can be explained by chromosome instability at the subtissue level. Med Hypotheses 68:716PubMedCrossRefGoogle Scholar
  38. Iourov IY, Vorsanova SG, Yurov YB (2008a) Chromosomal mosaicism goes global. Mol Cytogenet 1:26PubMedCrossRefGoogle Scholar
  39. Iourov IY, Vorsanova SG, Yurov YB (2008b) Molecular cytogenetics and cytogenomics of brain diseases. Curr Genomics 9:452–465PubMedCrossRefGoogle Scholar
  40. Iourov IY, Yurov YB, Vorsanova SG (2008c) Mosaic X chromosome aneuploidy can help to explain the male-to-female ratio in autism. Med Hypotheses 70:456PubMedCrossRefGoogle Scholar
  41. Iourov IY, Vorsanova SG, Liehr T, Kolotii AD, Yurov YB (2009a) Increased chromosome instability dramatically disrupts neural genome integrity and mediates cerebellar degeneration in the ataxia-telangiectasia brain. Hum Mol Genet 18:2656–2669PubMedCrossRefGoogle Scholar
  42. Iourov IY, Vorsanova SG, Liehr T, Yurov YB (2009b) Aneuploidy in the normal, Alzheimer’s disease and ataxia-telangiectasia brain: differential expression and pathological meaning. Neurobiol Dis 34:212–220PubMedCrossRefGoogle Scholar
  43. Iourov IY, Vorsanova SG, Yurov YB (2009c) Developmental neural chromosome instability as a possible cause of childhood brain cancers. Med Hypotheses 72:615–616PubMedCrossRefGoogle Scholar
  44. Iourov IY, Vorsanova SG, Yurov YB (2010) Somatic genome variations in health and disease. Curr Genomics 11:387–396PubMedCrossRefGoogle Scholar
  45. Iourov IY, Vorsanova SG, Yurov YB (2011) Genomic landscape of the Alzheimer’s disease brain: chromosome instability—aneuploidy, but not tetraploidy—mediates neurodegeneration. Neurodegener Dis 8:35–37PubMedGoogle Scholar
  46. Iourov IY, Vorsanova SG, Yurov YB (2012) Single cell genomics of the brain: focus on neuronal diversity and neuropsychiatric diseases. Curr Genomics 13(6):477–488PubMedCrossRefGoogle Scholar
  47. Kingsbury MA, Friedman B, McConnell MJ, Rehen SK, Yang AH, Kaushal D, Chun J (2005) Aneuploid neurons are functionally active and integrated into brain circuitry. Proc Natl Acad Sci U S A 102:6143–6147PubMedCrossRefGoogle Scholar
  48. Kingsbury MA, Yung YC, Peterson SE, Westra JW, Chun J (2006) Aneuploidy in the normal and diseased brain. Cell Mol Life Sci 63(22):2626–2641PubMedCrossRefGoogle Scholar
  49. Leitch AR (2000) Higher levels of organization in the interphase nucleus of cycling and differentiated cells. Microbiol Mol Biol Rev 64(1):138–152PubMedCrossRefGoogle Scholar
  50. Li L, McCormack AA, Nicholson JM, Fabarius A, Hehlmann R, Sachs RK, Duesberg PH (2009) Cancer-causing karyotypes: chromosomal equilibria between destabilizing aneuploidy and stabilizing selection for oncogenic function. Cancer Genet Cytogenet 188:1–25PubMedCrossRefGoogle Scholar
  51. Ly DH, Lockhar DJ, Lerne RA, Schultz PG (2000) Mitotic misregulation and human aging. Science 287:2486–2492PubMedCrossRefGoogle Scholar
  52. McConnell MJ, Kaushal D, Yang AH, Kingsbury MA, Rehen SK, Treuner K et al (2004) Failed clearance of aneuploid embryonic neural progenitor cells leads to excess aneuploidy in the Atm-deficient but not the Trp53-deficient adult cerebral cortex. J Neurosci 24:8090–8096PubMedCrossRefGoogle Scholar
  53. McKinnon PJ (2004) ATM and ataxia telangiectasia. EMBO Rep 5:772–776PubMedCrossRefGoogle Scholar
  54. Migliore L, Coppede F, Fenech M, Thomas P (2011) Association of micronucleus frequency with neurodegenerative diseases. Mutagenesis 26:85–92PubMedCrossRefGoogle Scholar
  55. Mosch B, Morawski M, Mittag A, Lenz D, Tarnok A, Arendt T (2007) Aneuploidy and DNA replication in the normal human brain and Alzheimer’s disease. J Neurosci 27:6859–6867PubMedCrossRefGoogle Scholar
  56. Muotri AR, Gage FH (2006) Generation of neuronal variability and complexity. Nature (Lond) 441:1087–1093CrossRefGoogle Scholar
  57. Potter H (2008) Down’s syndrome and Alzheimer’s disease: two sides of the same coin. Future Neurol 3:29–37CrossRefGoogle Scholar
  58. Potter H, Granic A, Iourov IY, Migliore L, Vorsanova SG, Yurov YB (2011) Alzheimer’s insight. The New Scientist 211(2824):32CrossRefGoogle Scholar
  59. Rehen SK, McConnell MJ, Kaushal D, Kingsbury MA, Yang AH, Chun J (2001) Chromosomal variation in neurons of the developing and adult mammalian nervous system. Proc Natl Acad Sci U S A 98:13361–13366PubMedCrossRefGoogle Scholar
  60. Rehen SK, Yung YC, McCreight MP, Kaushal D, Yang AH, Almeida BSV et al (2005) Constitutional aneuploidy in the normal human brain. J Neurosci 25(9):2176–2180PubMedCrossRefGoogle Scholar
  61. Robberecht C, Vanneste E, Pexsters A, D’Hooghe T, Voet T, Vermeesch JR (2010) Somatic genomic variations in early human prenatal development. Curr Genomics 11(6):397–401PubMedCrossRefGoogle Scholar
  62. Smith CL, Bolton A, Nguyen G (2010) Genomic and epigenomic instability, fragile sites, schizophrenia and autism. Curr Genomics 11(6):447–469PubMedCrossRefGoogle Scholar
  63. Soloviev IV, Yurov YB, Vorsanova SG, Fayet F, Roizes G, Malet P (1995) Prenatal diagnosis of trisomy 21 using interphase fluorescence in situ hybridization of post-replicated cells with site-specific cosmid and cosmid contig probes. Prenat Diagn 15:237–248PubMedCrossRefGoogle Scholar
  64. Spremo-Potrapevic B, Zivkovic L, Plecas-Solarovic B, Bajic VP (2011) Chromosome instability in Alzheimer’s disease. Arch Biol Sci 63:603–608CrossRefGoogle Scholar
  65. Taupin P (2011) Neurogenesis, NSCs, pathogenesis and therapies for Alzheimer’s disease. Front Biosci 3:178–190CrossRefGoogle Scholar
  66. Thomas P, Fenech M (2008) Chromosome 17 and 21 aneuploidy in buccal cells is increased with ageing and in Alzheimer’s disease. Mutagenesis 23:57–65PubMedCrossRefGoogle Scholar
  67. Vanneste E, Voet T, Le Caignec C, Ampe M, Konings P, Melotte C et al (2009) Chromosome instability is common in human cleavage-stage embryos. Nat Med 15:577–583PubMedCrossRefGoogle Scholar
  68. Vorsanova SG, Demidova IA, Ulas VY, Soloviev IV, Kazantzeva LZ, Yurov YB (1996) Cytogenetic and molecular-cytogenetic investigation of Rett syndrome: analysis of 31 cases. Neuroreport 8(1):187–189PubMedCrossRefGoogle Scholar
  69. 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
  70. Vorsanova SG, Kolotii AD, Iourov IY, Monakhov VV, Kirillova EA, Soloviev IV, Yurov YB (2005) Evidence for high frequency of chromosomal mosaicism in spontaneous abortions revealed by interphase FISH analysis. J Histochem Cytochem 53:375–380PubMedCrossRefGoogle Scholar
  71. 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
  72. Vorsanova SG, Iourov IY, Kolotii AD, Beresheva AK, Demidova IA, Kurinnaia OS et al (2010a) Chromosomal mosaicism in spontaneous abortions: analysis of 650 cases. Russ J Genet 46:1197–1200CrossRefGoogle Scholar
  73. 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
  74. Vorsanova SG, Yurov YB, Iourov IY (2010c) Human interphase chromosomes: a review of available molecular cytogenetic technologies. Mol Cytogenet 3:1PubMedCrossRefGoogle Scholar
  75. Weaver BA, Cleveland DW (2009) The role of aneuploidy in promoting and suppressing tumors. J Cell Biol 185:935–937PubMedCrossRefGoogle Scholar
  76. 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
  77. Westra JW, Peterson SE, Yung YC, Mutoh T, Barral S, Chun J (2008) Aneuploid mosaicism in the developing and adult cerebellar cortex. J Comp Neurol 507:1944–1951PubMedCrossRefGoogle Scholar
  78. Westra JW, Barral S, Chun J (2009) A reevaluation of tetraploidy in the Alzheimer’s disease brain. Neurodegener Dis 6:221–229PubMedCrossRefGoogle Scholar
  79. Westra JW, Rivera RR, Bushman DM, Yung YC, Peterson SE, Barral S, Chun J (2010) Neuronal DNA content variation (DCV) with regional and individual differences in the human brain. J Comp Neurol 518:3981–4000PubMedCrossRefGoogle Scholar
  80. Xu J, Zwaigenbaum L, Szatmari P, Scherer SW (2004) Molecular cytogenetics of autism. Curr Genomics 4:347–368CrossRefGoogle Scholar
  81. Yang Y, Herrup K (2007) Cell division in the CNS: protective response or lethal event in post-mitotic neurons? Biochim Biophys Acta 1772:457–466PubMedCrossRefGoogle Scholar
  82. Yang Y, Geldmacher DS, Herrup K (2001) DNA replication precedes neuronal cell death in Alzheimer’s disease. J Neurosci 21:2661–2668PubMedGoogle Scholar
  83. 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
  84. Yurov YB, Iourov IY, Monakhov VV, Soloviev IV, Vostrikov VM, Vorsanova SG (2005) The variation of aneuploidy frequency in the developing and adult human brain revealed by an interphase FISH study. J Histochem Cytochem 53:385–390PubMedCrossRefGoogle Scholar
  85. Yurov YB, Iourov IY, Vorsanova SG, Liehr T, Kolotii AD, Kutsev SI et al (2007a) Aneuploidy and confined chromosomal mosaicism in the developing human brain. PLoS One 2:e558PubMedCrossRefGoogle Scholar
  86. Yurov YB, Vorsanova SG, Iourov IY, Demidova IA, Beresheva AK, Kravetz VS et al (2007b) Unexplained autism is frequently associated with low-level mosaic aneuploidy. J Med Genet 44:521–525PubMedCrossRefGoogle Scholar
  87. Yurov YB, Iourov IY, Vorsanova SG, Demidova IA, Kravetz VS, Beresheva AK et al (2008) The schizophrenia brain exhibits low-level aneuploidy involving chromosome 1. Schizophr Res 98:139–147PubMedCrossRefGoogle Scholar
  88. Yurov YB, Iourov IY, Vorsanova SG (2009a) Neurodegeneration mediated by chromosome instability suggests changes in strategy for therapy development in ataxia-telangiectasia. Med Hypotheses 73:1075–1076PubMedCrossRefGoogle Scholar
  89. Yurov YB, Vorsanova SG, Iourov IY (2009b) GIN ‘n’ CIN hypothesis of brain aging: deciphering the role of somatic genetic instabilities and neural aneuploidy during ontogeny. Mol Cytogenet 2:23PubMedCrossRefGoogle Scholar
  90. Yurov YB, Vorsanova SG, Iourov IY (2010) Ontogenetic variation of the human genome. Curr Genomics 11:420–425PubMedCrossRefGoogle Scholar
  91. Yurov YB, Vorsanova SG, Iourov IY (2011a) The DNA replication stress hypothesis of Alzheimer’s disease. ScientificWorldJournal 11:2602–2612PubMedCrossRefGoogle Scholar
  92. 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
  93. 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
  94. Zekanowski C, Wojda U (2009) Aneuploidy, chromosomal missegregation, and cell cycle reentry in Alzheimer’s disease. Acta Neurobiol Exp 6:232–253Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  1. 1.Mental Health Research Center, Russian Academy of Medical SciencesMoscowRussia
  2. 2.Institute of Pediatrics and Children Surgery, Ministry of HealthMoscowRussia
  3. 3.Moscow City University of Psychology and EducationMoscowRussia

Personalised recommendations