April 24, 2024

NIH Launches $140 Million Effort to Investigate Genetic Variation in Normal Human Cells and Tissues

Press release

Thursday, May 11, 2023

The Common Fund Program will accelerate research into human development, aging and disease.

The National Institutes of Health is launching a new program, the Common Fund Somatic Mosaicism through Human Tissues (SMaHT) Network, that aims to transform our knowledge about how much genetic variation there is in our body’s cells and tissues. Somatic mosaicism is a type of genetic variation that arises when our somatic (non-reproductive) cells are genetically different from each other. This somatic genetic variation occurs when some of our cells accumulate changes in their DNA over time. Somatic mosaicism can alter cell function and influence human development, disease, aging, and other physiological measures throughout life. The SMaHT Network, with awards totaling US$140 million over five years depending on funding availability, seeks to discover and catalog the breadth of somatic mosaicism in human tissues.

“Because somatic mosaicism can occur in any type of cell in our body, it can have wide-reaching impacts on our health. The breadth of mosaicism’s reach makes it difficult for just one institute or center at NIH to address alone,” said Robert Eisinger, Ph.D, acting director of the NIH Division of Program Coordination, Planning, and Strategic Initiatives, which provides financial support and leadership. joint effort for the network through the NIH Common Fund. “This makes the study of somatic mosaicism a good fit for an NIH Common Fund program, as it was established to catalyze research within the broad mission of the NIH.”

Although somatic mosaicism can occur in all tissues, is a major contributor to cancer, and can be caused by both external 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 fundamental knowledge that will enable investigation into the role that somatic genetic variation plays in human development and aging, as well as into a wide range of diseases and disorders, including undiagnosed. of the brain, muscles, skin and immune system. Furthermore, 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 such as the Human Genome Project and the Common Fund Epigenomics Program, overcoming challenges in studying parts of our DNA that have long frustrated traditional DNA sequencing tools. For example, cell- and tissue-specific genetic changes often occur in rare populations of cells and may exist in repetitive regions of DNA 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 cutting-edge technologies to better detect somatic mosaicism in different types of cells and tissues and at all stages of human life.

Walter Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), noted that “advancing technologies to identify somatic mutations, including those due to the movement of transposable elements or so-called ‘jumping genes,’ along of time, will lead to a new understanding of age-related disorders.”

The NIH issued 22 awards to establish the SMaHT Network, components include:

  • Procurement center will collect a common pool of 10 to 15 tissues from 150 post-mortem human donors
  • Genome characterization centers to identify and describe the diversity of somatic genetic variation in tissues
  • Data analysis center to create a catalog of this somatic genetic variation and a database to visualize and analyze the variation that will be integrated with existing genetic tools and databases
  • Projects to develop tools to create new DNA sequencing and analysis technologies that address challenges in detecting rare genetic changes that occur in regions of repetitive DNA sequences and in small populations of cells
  • Organizational center to coordinate Network activities and distribute Network resources to the research community.

To ensure diverse representation, the SMaHT Network will collect tissue samples from a pool of human donors that include diverse ancestries and different life stages. The common set of tissues to be collected from each donor will represent different tissue types throughout the body and will likely include samples derived from the brain, blood, skin, muscle, colon, spleen, uterus, vas deferens, ovaries, and testes.

The SMaHT Network is an NIH-wide effort managed collaboratively by the NIH Common Fund, the National Human Genome Research Institute, the National Institute on Drug Abuse, the National Institute of Environmental Health Sciences, the National Institute of Mental Health and NINDS.

About the NIH Common Fund: The NIH Common Fund encourages collaboration and supports a range of exceptionally high-impact programs across the NIH. Common Fund programs are managed by the Office of Strategic Coordination in the Division of Program Coordination, Planning, and Strategic Initiatives in the Office of the Director of the NIH in partnership with NIH Institutes, Centers, and Offices. More information is available on the Common Fund website: https://commonfund.nih.gov.

About the National Institutes of Health (NIH):The NIH, the nation’s medical research agency, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research and is investigating the causes, treatments, and cures for common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery into Health®

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