Somatic Genome Variations

Abstract

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).

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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.

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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.

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