Created the largest atlas of human genetic mutations

The guide, created by a group of researchers at Oregon Health & Science University, is the most comprehensive ever created. The results of the work published in ‘Science’

A group of researchers from Oregon Health & Science University (Ohsu) created the largest atlas of genetic mutations in healthy human tissue. With hundreds of donors, the guide is the most comprehensive ever created and could lead to better diagnosis and treatment of diseases associated with ‘bad luck or bad habits’, the authors highlight. The results of the work are published in ‘Science’. The atlas is the largest ever, in terms of combined number of tissues and number of donors sampled, and points the way towards understanding the genetic basis of cancer-associated diseases and countless conditions related to cellular malfunctions, including aging. It could potentially be useful for reversing disease-causing genetic mutations, experts say.

And, speaking of genetic changes that underlie disease, “there are now a wide variety of technologies that allow us to make changes to the genome,” notes senior author Don Conrad, an associate professor at Ohsu School of Medicine. “It may be possible to change those mutations that we acquired through bad luck or bad habits and bring them back to how they were before.” The researchers generated the atlas using 54 tissue and cell typesall cataloged after the deaths of 948 people who donated their bodies to science for the National Institutes of Health (NIH) Genotype-Tissue Expression program.

Each person, experts observe, begins as a single cell at the moment of conception, carrying a blueprint of DNA inside the nucleus of that first fertilized cell. Using those original DNA instructions, the cell divides and replicates into vast groups of cells that form distinct tissues that perform unique functions in the body. At any one time, a person is made up of approximately 30 trillion cells, and over a lifetime that same person produces quadrillions of cells. Over time, a single cell is damaged repeatedly. In some cases, it repairs itself thousands of times a day. And “every now and then he makes a mistake while repairing the DNA, or something is lost and this change propagates,” explains Conrad. “Our work gives us a window into the extent to which these changes occur in different organs and tissues and during different periods of our lives.”

This situation is known as somatic mosaicism, and is the result of cells mutating from the original DNA blueprint. Until now, genetic research investigating mutations that occur post-zygotic, or after fertilization, has generally been conducted in biopsies of cancerous tissue such as skin melanomas and lung cancers, or in readily accessible tissue such as blood. The new atlas, on the other hand, opens up a field of investigation into the mutations that occur throughout life.

“Going from a single cell to a baby is an amazing process,” says lead author Nicole Rockweiler, now an assistant professor at the Broad Institute of Massachusetts Institute of Technology and Harvard University. “When you add layers of mutations that occur in such a major part of our lives, it’s amazing that we can come out of it quite well at the end of the gestation,” she reflects. To generate the new atlas, the researchers were able to track where mutations occurred by mapping them on a ‘developmental tree’, indexing them across tissues and across multiple people.

Experts found that many mutations arose systematically and somewhat predictably as people aged, although about 10% of mutations appeared to be the result of something intrinsic to an individual, whether it be genes or environment. Another observation was that most detectable mutations occurred later in life, although many occurred before birth. It’s still: “Some tissues, such as the esophagus and liver, acquire many mutations while others such as the brain acquire fewer”Rockweiler writes in a post on the Conrad Lab website describing the research. “This makes sense because the esophagus and liver are exposed to many environmental toxins; here the cells have to deliver the message in a noisy environment. Even a low number of mutations in the brain makes sense because the brain is mostly composed of non-replicating cells.”