Somatic Mosaicism Network Maps Mutations Across 19 Tissue Types to Build a Human Reference Catalogue
This Nature paper describes the Somatic Mosaicism across Human Tissues (SMaHT) Network, which aims to catalogue somatic mutations and clonal expansion patterns across 19 tissue sites from 150 healthy donors using novel detection technologies and computational tools. The consortium addresses the fundamental challenge that most somatic variants are present in only a small fraction of cells, requiring ultra-sensitive sequencing approaches. This reference catalogue will serve as a critical baseline for understanding the role of somatic mosaicism in aging and disease, with direct relevance to NGS-based diagnostic sensitivity and variant interpretation.
The original study
The Somatic Mosaicism across Human Tissues Network.
- Authors
- Coorens THH, Oh JW, Choi YA, Lim NS, Zhao B, Voshall A, et al.
- Journal
- Nature
- Type
- Journal Article, Review
- PMID
- 40604182
Original abstract
From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues Network, which aims to create a reference catalogue of somatic mutations and their clonal patterns across 19 different tissue sites from 150 non-diseased donors and develop new technologies and computational tools to detect somatic mutations and assess their phenotypic consequences, including clonal expansions. This strategy enables a comprehensive examination of the mutational landscape across the human body, and provides a comparison baseline for somatic mutation in diseases. This will lead to a deep understanding of somatic mutations and clonal expansions across the lifespan, as well as their roles in health, in ageing and, by comparison, in diseases.