Older fathers pass on more mutations to their kids than older mothers

A new study has shown that children of older parents are more likely to inherit "new" genetic mutations.

Fathers who have children late in life are most at risk of passing on more genetic mutations, which can trigger rare diseases, in their sperm to their children said the study that investigated the genomes of thousands of Icelandic parents and children.

New mutations are genetic alterations that appear for the first time in eggs rather than being carried for generations. They are key drivers of evolution but some can be harmful.

They are key drivers of evolution in both animals and plants, but can be harmful.

To find out, Stefánsson and his colleagues sequenced the genomes for so-called "de novo" mutations in the DNA of 14,688 Icelanders. 

The Icelandic study identified a total of 108,778 high quality DNMs with an average of 70.3 per family.

With each year of increasing age, the number of de novo mutations inherited from mothers increased by 0.37 - a quarter of the 1.51 per year rate from fathers.

An extraordinarily large percentage of rare diseases in children are rooted in mutations that are not found in their parents,” says Kári Stefánsson of deCODE genetics, a genetics company based in Iceland.

It’s important to figure out where these mutations are coming from.

The team used two different approaches that involved comparing the genome sequences of individuals with those of their parents, children and siblings.

If a sequence is not present in the parents but is present in the child, then it’s new,” says Stefánsson.

They discovered that 80 per cent of new mutations come from the father, and that the number of mutations increases in line with the age of the parents.

This is an important new chapter in our ongoing work to understand the mechanisms driving genomic diversity and through that the evolution of our species, said Dr Kari Stefansson.

"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.

The findings are published in the journal Nature.