Scientists Evaluate Methods for Detecting Rare DNA Mutations Linked to Aging and Cancer

Genetic differences between the cells and tissues of the same individual are known as somatic mosaicism. Unlike inherited DNA variants, which are passed down from parents and are present in virtually all cells of the body, somatic mutations arise during a person's lifetime and affect only certain cells.

Many of these changes are harmless, but some are associated with the development of disease. To determine which variants may pose a health risk, scientists first need to establish which DNA changes commonly occur in healthy individuals.

The researchers evaluated computational tools designed to detect rare genetic variants. To do so, they used, among other resources, data from international human genome research projects and generated millions of artificial somatic mutations to test the accuracy of the methods.

The study showed that the most comprehensive picture of genetic mosaicism can be obtained by combining three approaches: DNA sequencing from tissue samples, single-cell analysis, and a method capable of detecting changes in both copies of a DNA molecule with high precision.

"We understand that every person is a genetic mosaic, but we need to determine the spectrum of normal somatic changes. This will help us identify which of them may lead to disease and find ways to reduce the risks," explained study leader Ting Wang.

The research is being conducted as part of the national Somatic Mosaicism across Human Tissues (SMaHT) research network, supported by the US National Institutes of Health. The next stage will involve analyzing samples from multiple tissues collected from 150 donors of different ancestries and ages to investigate how somatic changes are distributed throughout the body over a person's lifetime.