Older parents pass down more genetic mutations

Parents pass on more new genetic mutations to their children with age, and fathers pass on more than mothers, according to a study.

While mothers passed on a new mutation for every three years of age, fathers passed on a new mutation for every eight months of age. Most of these will not have any effect, yet some may contribute to genetic diseases.

'An extraordinarily large percentage of rare diseases in children are rooted in mutations that are not found in their parents,' said Dr Kári Stefánsson of deCODE genetics, the Icelandic company which carried out the study, published in Nature.

Mutations can be inherited by children if they occur in the sperm or egg cells of their parents. The researchers looked for these de novo mutations - genetic mutations in an individual that do not appear in either parent - in a comparison of the genomes of 1548 Icelanders, their parents, and for 225 individuals at least one of their children. They identified 108,778 de novo mutations overall, with about 70 per family.

New mutations occurred at higher rates as parents got older, with four times more coming from fathers than from mothers with every passing year of age.

This difference is likely because of the ways that sperm and eggs are produced. A woman is already born with all her eggs, whereas sperm are produced throughout a man's life by cell division, which can introduce errors in DNA replication.

'This is elegant work, but should come as no real surprise,' said Allan Pacey, professor of andrology at the University of Sheffield. 'We have known for many years that the risk of having a child with a medical condition of genetic origin increases noticeably with the father's age at conception. It is for this reason that there is a recommended upper age limit for sperm donors (currently 40 years) in the UK.'

As well as a difference in the number of mutations between men and women, the researchers also found a difference in the types of mutations. Those from the mother tended to be clustered together in parts of the genome.

'Although the majority of new mutations reported in this study have come from the fathers, the most striking new insights are from the extra mutations that occur in the eggs of older mothers,' said Professor Martin Taylor of the University of Edinburgh, UK. 'This new paper shows that many, and perhaps even most, of those extra mutations from older mothers occur in groups on the same DNA strand at the same time.'

'The study will be important for our understanding of human evolution and for our understanding of some rare diseases,' said Professor Pacey. 'However, for me, it simply reminds me of why we should always encourage men and women to have their children as early in their lives as possible.'