Yonsei researcher contributes to global map of somatic mutations in healthy human tissues

A global research consortium has unveiled a detailed map of somatic cell mutations across the human body -- offering new insights into how mutations accumulate with age and contribute to disease.

Professor Oh Ji-won

Professor Oh Ji-won of the Department of Anatomy at Yonsei University College of Medicine contributed as co–corresponding author to the study, which was published in Nature (IF 48.5) as part of the U.S. National Institutes of Health’s international project Somatic Mosaicism across Human Tissues (SMaHT).

Throughout life, somatic mutations gradually accumulate in human tissues. These mutations are linked not only to aging but also to a wide range of diseases, including cancer, cardiovascular disease, and neurological disorders.

Until now, few studies have systematically examined the distribution, nature, and frequency of mutations across a broad range of normal human tissues, as most somatic genomic research has focused on cancer samples or surgical specimens.

The research team analyzed 19 tissue types from non-diseased adult post-mortem donors -- including brain, heart, lungs, liver, colon, skin, blood, gonads, and reproductive organs -- collected through rapid autopsy within 24 hours of death.

The samples were analyzed using state-of-the-art techniques such as Duplex Sequencing and Single-cell Genomics, which are far more sensitive than conventional methods. Duplex Sequencing, in particular, reads both strands of DNA and considers only mutations confirmed on both, thereby minimizing errors.

By conducting detailed genomic analyses, the study revealed how somatic mutation patterns vary across tissues and with age. The researchers successfully detected rare somatic mutations in healthy tissues and examined clonal expansion, or the repeated division of a single mutated cell over time.

What makes this map unique is its focus on mutations in healthy individuals, rather than patients with disease. This baseline dataset may serve as a foundational reference for identifying early mutational events involved in the development of various diseases.

“The large-scale data generated by this study will be shared with researchers worldwide through an international database,” said Professor Oh. “Careful analysis of these subtle mutations may yield valuable insights into aging, heart disease, dementia, and more.”