Postzygotic mutations and where to find them - Recent advances and future implications in the field of non-neoplastic somatic mosaicism

Abstract

The technological progress of massively parallel sequencing (MPS) has triggered a remarkable development in the research on postzygotic mutations. Although the overwhelming majority of studies in the field focus on oncogenesis, non-neoplastic diseases are attracting more and more attention. The aim of this review was to summarize some of the most recent findings in the field of somatic mosaicism in diseases other than neoplastic events. We discuss the abundance and role of postzygotic mutations, with a special emphasis on disorders which occur only in a mosaic form (obligatory mosaic diseases; OMDs). Based on the list of OMDs compiled from the published literature and three databases (OMIM, Orphanet and MosaicBase), we demonstrate the prevalence of cancer-related genes across OMDs and suggest other sources to further explore OMDs and OMD-related genes. Additionally, we comment on some practical aspects related to mosaic diseases, such as approaches to tissue sampling, the MPS coverage required to detect variants at a very low frequency, as well as on bioinformatic and molecular tools dedicated to detect somatic mutations in MPS data.

Keywords: Mosaic disease; Mosaicism; Postzygotic mutation; Single nucleotide variant; Somatic mutation; Somatic variant.