Somatic genetic variation in healthy tissue and non-cancer diseases

Abstract

Somatic genetic variants have been studied for several years mostly concerning cancer, where they contribute to its origin and development. It is also clear that the somatic variants load is greater in aged individuals in comparison to younger ones, pointing to a cause/consequence of the senescence process. More recently, researchers have focused on the role of this type of variation in healthy tissue and its dynamics in cell lineages and different organs. In addition, somatic variants have been described to contribute to monogenic diseases, and the number of evidences of their role in complex disorders is also increasing. Thanks to recent advances in next-generation sequencing technologies, this type of genetic variation can be now more easily studied than in the past, although we still face some important limitations. Novel strategies for sampling, sequencing and filtering are being investigated to detect these variants, although validating them with an orthogonal approach will most likely still be needed. In this review, we aim to update our knowledge of somatic variation detection and its relation to healthy tissue and non-cancer diseases.

Fig. 1. Sample types (green), sequencing approach (blue) and methodology (grey) used to study somatic variants along time.

Gradient in each box approximately represents the intensivity of use at different periods. DOP-PCR degenerate oligonucleotide-primer PCR, MDA multiple displacement amplification, MALBAC multiple annealing and looping-based amplification, PTA primary templatedirected amplification, UID unique identifiers, UMI unique molecular identifiers.