Rethinking the prosaicism of mosaicism; is it in us?

Abstract

Exponential advances in the quantitation of DNA variation and epigenetic states seem poised to convert much of biological research into a statistical exercise. But these developments also invite us to reimagine well-worn biological concepts on a grander scale. Somatic mosaicism refers to postzygotic mutations persisting in the individual, occasionally conspicuous to dermatologists as Blaschkoid, checkerboard, phylloid and patchy morphologies. A thoughtful examination of cutaneous mosaicism suggests, however, that virtually all of us may be somatic mosaics. Such genetic variability within individuals might explain localized presentations of disease and implies that some tissues literally evolve throughout life. We discuss here (i) the likely ubiquity of somatic mosaicism, (ii) the broad range of possible biological consequences and (iii) how experimentalists and clinicians may begin establishing genotypeto-phenotype correlates.

Detecting somatic mosaicism: considerations and clinical implications

“…First and foremost, mosaicism has been underestimated within the population. Individuals accumulate mutations over their lifetime that may not have a phenotypic effect; as such, we would expect to find mosaicism in phenotypically normal individuals . Similarly, loss of the X chromosome is seen in normal females as they age which means that having some 45X cells does not mean the patient has TS.…”

“…Individuals accumulate mutations over their lifetime that may not have a phenotypic effect; as such, we would expect to find mosaicism in phenotypically normal individuals (84). First and foremost, mosaicism has been underestimated within the population.…”

Symmetric Plantar Melanocytic Nevi - Site-Specific Phenomenon or Pure Chance

“…It has been proposed that predilection sites might represent a consequence of a ubiquitous somatic mosaicism [17]. In the case of neoplastic (benign or malignant) skin conditions, a symmetric distribution of two or more lesions is much less frequent.…”

Genetics and Epigenetics of the Skin Meet Deep Sequence

“…These diverse examples imply that occult, localized genetic variation probably both enhances and ameliorates human pathology constantly (Cho, 2010). Detecting small populations of mutant cells demands the screening of exomes for aberrant populations less than 1 in 10,000 affordably and reliably.…”