Department of Medical Genetics, Medical University of Warsaw, ul. Pawińskiego 3c, 02-106 Warsaw, Poland.
Institute of Computer Science, Warsaw University of Technology, Nowowiejska 15/19, 00-665 Warsaw, Poland.
Mutat Res Rev Mutat Res. 2022 Jul-Dec;790:108426. doi: 10.1016/j.mrrev.2022.108426. Epub 2022 Jun 9.
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.
大规模并行测序（MPS）技术的进步引发了后合子突变研究的显著发展。尽管该领域的绝大多数研究都集中在肿瘤发生上，但非肿瘤性疾病越来越受到关注。本综述旨在总结除肿瘤事件以外的疾病中体细胞镶嵌性的一些最新发现。我们讨论了后合子突变的丰度和作用，特别强调了仅以镶嵌形式发生的疾病（强制性镶嵌疾病；OMD）。基于从已发表文献和三个数据库（OMIM、Orphanet 和 MosaicBase）中编译的 OMD 列表，我们展示了癌症相关基因在 OMD 中的普遍性，并提出了其他来源以进一步探索 OMD 和 OMD 相关基因。此外，我们还评论了一些与镶嵌疾病相关的实际方面，例如组织采样方法、检测非常低频变异所需的 MPS 覆盖范围，以及专门用于在 MPS 数据中检测体细胞突变的生物信息学和分子工具。
