OHSU Scientists Develop Large Atlas of Human Tissue Mutations

Researchers at Oregon Health & Science University (OHSU) created the largest atlas of post-zygotic genome mutations in healthy human tissue ever assembled, according to a study published in the journal Science. This advancement could lead to new ways of diagnosing and treating genetic diseases.

The atlas is the largest ever in terms of the combined number of tissues and donors sampled, opening a field of inquiry into mutations occurring throughout the lifespan. 

The atlas was generated using 54 tissue and cell types compiled after death from 948 individuals who donated their bodies to the National Institute of Health’s Genotype-Tissue Expression Program. Somatic mosaicism, which results from cells mutating from the original DNA blueprint, is a situation where individual cells are repeatedly damaged. Until now, genetic research investigating mutations that occur post-zygotically has generally been conducted in biopsies of cancerous tissue, such as skin melanomas and lung tumors or easily accessible tissues, like blood.

The OHSU team developed a computational method using bulk RNA sequencing to characterize the mutations in a massive catalog of tissue samples throughout the body. They were able to trace the point at which mutations occurred by mapping them to a “developmental tree,” indexing them across tissues and among many people.

They found many mutations arose systematically and somewhat predictably as people age. However, roughly 10% of mutations appeared to result from something intrinsic to an individual, whether genes or environment. Notably, they also found most detectable mutations occurred later in life, although many occurred before birth.

This study points the way toward understanding the genetic underpinnings of cancer-associated disease, as well as various other conditions caused by cellular malfunction, including aging. The atlas could help diagnose and reverse genetic mutations causing disease, allowing scientists to develop new therapies for genetic disorders and other conditions resulting from post-zygotic mutations.

Overall, the researchers’ findings are a critical step forward in our understanding of the genetics of human disease. While there is still much to learn about post-zygotic mutations, this study is an important first step in the right direction.