De Novo Mutations

James Radke

Today in Nature,  genetic researchers posted analysis of whole-genome data from 14,000 people in Iceland to better understand the origins of genetic mutations that appear for the first time in a family and present in a sperm or egg cell, and referred to as de novo mutations.

The researchers from deCODE, an Icelandic-based company dedicated to analyzing the human genome, identified a total of 108,778 de novo mutations and were able to determine the parent of origin for 42,961 of those mutations. In general, age was a critical factor in the risk of a mutation. The number of de novo mutations from mothers increased by 0.37 per year of age whereas in fathers, they increased by 1.51.

The company intends to create new means of diagnosing, treating and preventing diseases.

The study also noted that while fathers pass along about 4 times as many new mutations as mothers do, the contribution from the egg is strong in an estimated 10% of the genome that is highly prone to DNA breaks. In other words, the male contribution is widespread but the female contribution is more focused.

The study did not determine whether any of the mutations were associated with a medical condition and, while de novo mutations are fundamental to evolution, they can also lead to rare conditions.

In a news release, Kari Stefansson, CEO of deCODE and senior author said, "De novo or new mutations provide an important part of the substrate for evolution, launching a constant flow of new versions of the human genome into the environment. However, they are also believed to be responsible for the majority of cases of rare diseases of childhood. Providing a comprehensive catalogue of such mutations from across an entire population is therefore not just scientifically interesting but also an important contribution to improving rare disease diagnostics."

Jónsson H, Sulem P, Kehr B, et al. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature. Published online September 20, 2017. doi:10.1038/nature24018

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