Somatic Genome Variations


The genome of somatic cells is susceptible to change through ontogeny. These variations can take a variety of forms and occur through different mechanisms. Stochastic intercellular variations of the genome are suggested to be involved in a number of critical biological processes (pre‐natal development, cell number regulation, cell death and aging). However, somatic genome variations have been shown to be involved in pathogenesis of a broad spectrum of human diseases (from chromosomal and monogenic diseases to complex disorders). Nonetheless, the contribution of somatic genome variations to human biodiversity and disease is usually underappreciated. The latter is due to consistent questioning the possibility of techniques used for uncovering somatic genome variation. Therefore, technological aspects of studying intercellular variation of the human genome remain an additional important issue for understanding the role of somatic mosaicism in health and disease.

Key Concepts:

  • The cellular genome is highly variable both at molecular and at chromosomal level.

  • Somatic variation of the human genome is a likely mechanism for biodiversity either at intercellular or at interindividual level.

  • A number of critical biological processes (pre‐natal development, cell number regulation, cell death and aging) seem to be mediated by somatic genome variations.

  • According to current concepts, the commonest type of intercellular genome variations are those manifested as changes of chromosome numbers (aneuploidy or polyploidy).

  • Somatic genome variations are known to contribute to pathogenesis of hereditary and chromosomal diseases.

  • Intercellular genome variation is a highly probable mechanism of complex disorders (i.e. diseases of the brain and immune system), pre‐natal mortality and cancer.

  • Understanding of the way to uncover somatic genome variations is an important issue for determining the contribution to intercellular/interindividual diversity in health and disease as well as their functional consequences.

Keywords: somatic genome variations; genome instability; chromosome instability; ontogeny; biodiversity; aneuploidy; molecular cytogenetics

Figure 1.

Molecular cytogenetic ways to uncover somatic genome variations. (a) Array CGH detection of mosaicism for an isochromosome 12p (supernumerary short arm of chromosome 12). (b) Two‐colour (two‐probe) interphase FISH demonstrating a gain (trisomy) of chromosome 15 in an interphase nucleus of the post‐mortem brain. (c) Multiprobe interphase FISH demonstrating a gain (trisomy) of chromosome 9 in an interphase nucleus of the post‐mortem brain. (d) Multiprobe interphase FISH demonstrating tetraploidy (four haploid sets of chromosomes in a cell – four signals for chromosome 1; two signals for chromosome X and two signals for chromosome Y) in an interphase nucleus of the post‐mortem brain. (e) Interphase chromosome‐specific multicolour banding demonstrating a loss (monosomy) of chromosome 21 in an interphase nucleus of the Alzheimer disease brain. (f) Interphase chromosome‐specific multicolour banding demonstrating normal number of chromosomes 16 (disomy) in an interphase nucleus of the developing human brain. (g) Interphase chromosome‐specific multicolour banding demonstrating a gain of chromosome 16 (trisomy) in an interphase nucleus of the developing human brain. (b–e) is reproduced from Vorsanova et al. and (f–g) reproduced from Yurov et al. (open access articles distributed under the terms of the Creative Commons Attribution License).



Aguilera A and Gómez‐González B (2008) Genome instability: a mechanistic view of its causes and consequences. Nature Reviews. Genetics 9(3): 204–217.

Arendt T, Brückner MK, Mosch B and Lösche A (2010) Selective cell death of hyperploid neurons in Alzheimer's disease. American Journal of Pathology 177(1): 15–20.

Baranzini SE, Mudge J, van Velkinburgh JC et al. (2010) Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature 464(7293): 1351–1356.

De S (2011) Somatic mosaicism in healthy human tissues. Trends in Genetics 27(6): 217–223.

van Echten‐Arends J, Mastenbroek S, Sikkema‐Raddatz B et al. (2011) Chromosomal mosaicism in human preimplantation embryos: a systematic review. Human Reproduction Update 17(5): 620–627.

Erickson RP (2003) Somatic gene mutation and human disease other than cancer. Mutation Research 543(2): 125–136.

Gericke GS (2008) An integrative view of dynamic genomic elements influencing human brain evolution and individual neurodevelopment. Medical Hypotheses 71(3): 360–373.

Gordon DJ, Resio B and Pellman D (2012) Causes and consequences of aneuploidy in cancer. Nature Reviews. Genetics 13(3): 189–203.

Hall JG (1988) Review and hypotheses: somatic mosaicism: observations related to clinical genetics. American Journal of Human Genetics 43(4): 355–363.

Heng HH (2010) Missing heritability and stochastic genome alterations. Nature Reviews. Genetics 11(11): 813.

Heng HH, Stevens JB, Bremer SW et al. (2011) Evolutionary mechanisms and diversity in cancer. Advances in Cancer Research 112: 217–253.

Hochstenbach R, Buizer‐Voskamp JE, Vorstman JA and Ophoff RA (2011) Genome arrays for the detection of copy number variations in idiopathic mental retardation, idiopathic generalized epilepsy and neuropsychiatric disorders: lessons for diagnostic workflow and research. Cytogenetic and Genome Research 135(3–4): 174–202.

Hultén MA, Patel SD, Tankimanova M et al. (2008) On the origin of trisomy 21 Down syndrome. Molecular Cytogenetics 1: 21.

Inoue N, Murakami Y and Kinoshita T (2003) Molecular genetics of paroxysmal nocturnal hemoglobinuria. International Journal of Hematology 77(2): 107–112.

Iourov IY, Liehr T, Vorsanova SG and Yurov YB (2007) Interphase chromosome‐specific multicolor banding (ICS‐MCB): a new tool for analysis of interphase chromosomes in their integrity. Biomolecular Engineering 24(4): 415–417.

Iourov IY, Vorsanova SG, Liehr T, Kolotii AD and Yurov YB. (2009a) Increased chromosome instability dramatically disrupts neural genome integrity and mediates cerebellar degeneration in the ataxia‐telangiectasia brain. Human Molecular Genetics 18(14): 2656–2669.

Iourov IY, Vorsanova SG, Liehr T and Yurov YB (2009b) Aneuploidy in the normal, Alzheimer's disease and ataxia‐telangiectasia brain: differential expression and pathological meaning. Neurobiology of Disease 34(2): 212–220.

Iourov IY, Vorsanova SG and Yurov YB (2006) Chromosomal variation in mammalian neuronal cells: known facts and attractive hypotheses. International Review of Cytology 249: 143–191.

Iourov IY, Vorsanova SG and Yurov YB (2008a) Chromosomal mosaicism goes global. Molecular Cytogenetics 1: 26.

Iourov IY, Vorsanova SG and Yurov YB (2008b) Molecular cytogenetics and cytogenomics of brain diseases. Current Genomics 9(7): 452–465.

Iourov IY, Vorsanova SG and Yurov YB (2010) Somatic genome variations in health and disease. Current Genomics 11(6): 387–396.

Jackson‐Cook C (2011) Constitutional and acquired autosomal aneuploidy. Clinics in Laboratory Medicine 31(4): 481–511.

Kennedy SR, Loeb LA and Herr AJ (2012) Somatic mutations in aging, cancer and neurodegeneration. Mechanisms of Ageing and Development

Kingsbury MA, Yung YC, Peterson SE, Westra JW and Chun J (2006) Aneuploidy in the normal and diseased brain. Cellular and Molecular Life Sciences 63(22): 2626–2641.

Liehr T (2009) Fluorescence In Situ Hybridization – Application Guide. Berlin‐Heidelberg: Springer‐Verlag.

Liehr T (2012) Small Supernumerary Marker Chromosomes (sSMC) – A Guide for Human Geneticists and Clinicians. Heidelberg: Springer.

Lindhurst MJ, Sapp JC, Teer JK et al. (2011) A mosaic activating mutation in AKT1 associated with the Proteus syndrome. New England Journal of Medicine 365(7): 611–619.

Mkrtchyan H, Gross M, Hinreiner S et al. (2010) Early embryonic chromosome instability results in stable mosaic pattern in human tissues. PLoS One 5(3): e9591.

Notini AJ, Craig JM and White SJ (2008) Copy number variation and mosaicism. Cytogenetic and Genome Research 123(1–4): 270–277.

Pamphlett R, Morahan JM, Luquin N and Yu B (2011) Looking for differences in copy number between blood and brain in sporadic amyotrophic lateral sclerosis. Muscle and Nerve 44(4): 492–498.

Piotrowski A, Bruder CE, Andersson R et al. (2008) Somatic mosaicism for copy number variation in differentiated human tissues. Human Mutation 29(9): 1118–1124.

Pleasance ED, Cheetham RK, Stephens PJ et al. (2010) A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 463(7278): 191–196.

Rodríguez‐Santiago B, Malats N, Rothman N et al. (2010) Mosaic uniparental disomies and aneuploidies as large structural variants of the human genome. American Journal of Human Genetics 87(1): 129–138.

Scherer SW, Lee C, Birney E et al. (2007) Challenges and standards in integrating surveys of structural variation. Nature Genetics 39(suppl. 7): S7–S15.

Sheltzer JM and Amon A (2011) The aneuploidy paradox: costs and benefits of an incorrect karyotype. Trends in Genetics 27(11): 446–453.

Stetten G, Escallon CS, South ST et al. (2004) Reevaluating confined placental mosaicism. American Journal of Medical Genetics A 131(3): 232–239.

Vanneste E, Voet T, Le Caignec C et al. (2009) Chromosome instability is common in human cleavage‐stage embryos. Nature Medicine 15(5): 577–583.

Vorsanova SG, Kolotii AD, Iourov IY et al. (2005) Evidence for high frequency of chromosomal mosaicism in spontaneous abortions revealed by interphase FISH analysis. Journal of Histochemistry and Cytochemistry 53(3): 375–380.

Vorsanova SG, Yurov YB and Iourov IY (2010a) Human interphase chromosomes: a review of available molecular cytogenetic technologies. Molecular Cytogenetics 3: 1.

Vorsanova SG, Yurov YB, Soloviev IV and Iourov IY (2010b) Molecular cytogenetic diagnosis and somatic genome variations. Current Genomics 11(6): 440–446.

Wang W, Bu B, Xie M et al. (2009) Neural cell cycle dysregulation and central nervous system diseases. Progress in Neurobiology 89(1): 1–17.

Weier JF, Weier HU, Jung CJ et al. (2005) Human cytotrophoblasts acquire aneuploidies as they differentiate to an invasive phenotype. Developmental Biology 279(2): 420–432.

Westra JW, Peterson SE, Yung YC et al. (2008) Aneuploid mosaicism in the developing and adult cerebellar cortex. Journal of Comparative Neurology 507(6): 1944–1951.

Westra JW, Rivera RR, Bushman DM et al. (2010) Neuronal DNA content variation (DCV) with regional and individual differences in the human brain. Journal of Comparative Neurology 518(19): 3981–4000.

Wyandt HE and Tonk VS (2012) Human Chromosome Variation: Heteromorphism and Polymorphism. Dordrecht: Springer.

Yurov YB, Iourov IY, Monakhov VV et al. (2005) The variation of aneuploidy frequency in the developing and adult human brain revealed by an interphase FISH study. Journal of Histochemistry and Cytochemistry 53(3): 385–390.

Yurov YB, Iourov IY, Vorsanova SG et al. (2007a) Aneuploidy and confined chromosomal mosaicism in the developing human brain. PLoS One 2(6): e558.

Yurov YB, Iourov IY, Vorsanova SG et al. (2008) The schizophrenia brain exhibits low‐level aneuploidy involving chromosome 1. Schizophrenia Research 98(1–3): 139–147.

Yurov YB, Vorsanova SG, Iourov IY et al. (2007b) Unexplained autism is frequently associated with low‐level mosaic aneuploidy. Journal of Medical Genetics 44(8): 521–525.

Yurov YB, Vorsanova SG and Iourov IY (2009) GIN'n'CIN hypothesis of brain aging: deciphering the role of somatic genetic instabilities and neural aneuploidy during ontogeny. Molecular Cytogenetics 2: 23.

Yurov YB, Vorsanova SG and Iourov IY (2010) Ontogenetic variation of the human genome. Current Genomics 11(6): 420–425.

Yurov YB, Vorsanova SG and Iourov IY (2011) The DNA replication stress hypothesis of Alzheimer's disease. Scientific World Journal 11: 2602–2612.

Zupanc GK (2008) Adult neurogenesis and neuronal regeneration in the brain of teleost fish. Journal of Physiology (Paris) 102(4–6): 357–373.

Further Reading

Dumanski JP and Piotrowski A (2012) Structural genetic variation in the context of somatic mosaicism. Methods in Molecular Biology 838: 249–272.

Erickson RP (2010) Somatic gene mutation and human disease other than cancer: an update. Mutation Research 705(2): 96–106.

Feuk L, Carson AR and Scherer SW (2006) Structural variation in the human genome. Nature Review. Genetics 7(2): 85–97.

Heng HH, Liu G, Stevens JB et al. (2011) Decoding the genome beyond sequencing: the new phase of genomic research. Genomics 98(4): 242–252.

Iourov IY, Vorsanova SG and Yurov YB (2006) Intercellular genomic (chromosomal) variations resulting in somatic mosaicism: mechanisms and consequences. Current Genomics 7(7): 435–446.

Robberecht C, Fryns JP and Vermeesch JR (2010) Piecing together the problems in diagnosing low‐level chromosomal mosaicism. Genome Medicine 2(7): 47.

Youssoufian H and Pyeritz RE (2002) Mechanisms and consequences of somatic mosaicism in humans. Nature Reviews. Genetics 3(10): 748–758.

Yurov YB and Iourov IY (2010) Hot topic issue on somatic genome variations. Current Genomics 11(6): 377–480.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Iourov, Ivan Y, Vorsanova, Svetlana G, and Yurov, Yuri B(Jun 2012) Somatic Genome Variations. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023889]