On May 11, 2023, the National Institutes of Health (NIH) announced launching a new program, the Common Fund’s Somatic Mosaicism Across Human Tissues (SMaHT) Network, that aims to transform our knowledge of how much genetic variation there is in the cells and tissues throughout our bodies. Somatic mosaicism can alter how cells function and may influence human development, disease, aging, and other physiological measures across the lifespan.  The SMaHT Network, with awards totaling $140 million dollars over five years, pending availability of funds, seeks to discover and catalog the breadth of somatic mosaicism in human tissues.

Although somatic mosaicism can occur in all tissues, is a major contributor to cancer, and can be caused by both outside exposures and a person’s own internal biological processes, its full impact on human health and disease is unknown. By cataloging somatic mosaicism in normal human tissues, the SMaHT Network will provide foundational knowledge that will enable research on the role that somatic genetic variation plays in human development and aging, as well as a wide range of diseases and disorders, including undiagnosed diseases and disorders of the brain, muscle, skin, and immune system. Additionally, given the contribution of somatic cell mutations to cancer, this effort has the potential to support President Biden’s goal of ending cancer as we know it as part of the Cancer Moonshot.

The SMaHT Network builds on other landmark projects, like the Human Genome Project and the Common Fund’s Epigenomics Program, by overcoming challenges to studying parts of our DNA that have long thwarted traditional DNA sequencing tools. For instance, cell- and tissue-specific genetic changes often occur in rare populations of cells and can exist in repetitive DNA regions that are difficult to characterize reliably. Furthermore, the extent of somatic mosaicism in humans may be influenced by the relative timing of the genetic change. The SMaHT Network will develop state-of-the-art technologies to better detect somatic mosaicism in different cell types and tissues and across human life stages.