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Review
. 2017 Feb:42:8-13.
doi: 10.1016/j.gde.2016.12.002. Epub 2017 Jan 6.

The ageing genome, clonal mosaicism and chronic disease

Mitchell J Machiela  1 , Stephen J Chanock  2
Affiliations
Review

The ageing genome, clonal mosaicism and chronic disease

Mitchell J Machiela et al. Curr Opin Genet Dev. 2017 Feb.

Abstract

Clonal mosaicism arises when a postzygotic mutational event is detectable in subpopulations of cells as an alternative genotype while not present in the germline genome. Although described in a subset of pediatric disorders, new genomic technologies have detected higher than anticipated frequencies of clonal mosaicism in adult population studies, stimulating investigation as to how clonal mosaicism could contribute to chronic human diseases, such as cancer, diabetes and neurodegenerative disorders. It has also been postulated to be an important mechanism for functional cellular diversity, including the brain. Early studies have characterized the spectrum of detectable mosaic alterations and have begun to investigate whether detectable mosaicism could be important as an overall biomarker for risk or in the case of hematologic cancers, identification of preleukemic clones.

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Figures

Figure 1
Figure 1
Depiction of a genetically normal cellular population that acquires a somatic mutation and clonally expands to daughter cells to form a mosaic cellular population.
Figure 2
Figure 2
Exploring two biologically plausible models for the acquisition of mosaicism. In the first model (a), a somatic event is acquired early in development during periods of rapid cellular growth and division, but the aberrant cells remain at low cellular proportions until later in life when changes in the cellular environment confer a selective advantage of aberrant clones over normal cells allowing them to expand to a detectable proportion of the cellular population. In the second model (b), somatic events are acquired later in life and soon after clonally expand to become a detectable proportion of the cellular population.
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