Nine Processes that Give Rise to Genetic Mutations Identified

A new multi-institutional study led by investigators at Harvard Medical School and Brigham and Women’s Hospital has pinpointed nine processes during which most human genetic mutations tend to arise. The work, published in Science, is based on an analysis of 400 million rare DNA human variants and represents one of the most comprehensive computational efforts to explore heritable genomic variations.

“Genetic mutations are a rare yet inevitable and, indeed essential, part of the development and propagation of the human species—they create genetic diversity, fuel evolution, and occasionally cause genetic diseases,” said study lead investigator Shamil Sunyaev. “Harnessing the power of computation and big data, we analyzed genomic variations and identified a set of biologic processes responsible for the vast majority of heritable human mutations,” added Sunyae. 

The research identified new mutation-fueling mechanisms and some that were already known. One mechanism was related to inaccurate copying of DNA, another was related to chemical damage occurring to the DNA. The analysis also pinpointed a machinery involved in human gene regulation as a frequent culprit in mutations. This machinery is particularly active during early embryonic development, and most of the mutations introduced by the machinery occur during this period. In one surprising finding, the researchers identified a mutation-driving mechanism that was not related to DNA copying and cellular division—processes that are prone to mutation-causing glitches. This previously unsuspected mechanism leads to mutations in egg cells stored in the ovaries.  

The researchers are now working to incorporate some of the results in a model of human-mutation rate along the genome in an effort to help predict the chance that a specific mutation would occur at a specific location in the genome. The goal is to help in the analysis of disease mutations and in the discovery of genes causing rare diseases. The model may also serve to highlight genes of key importance to human health and survival.