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Father's age strongest predictor of genetic mutations

28 August 2012
Appeared in BioNews 670

Children of older fathers inherit more genetic mutations than those of younger fathers, according to Icelandic scientists.

New sperm cells are continuously made from stem cells in the testes. The stem cells multiply by copying their DNA, but during the process mistakes can occur, which form mutations in the DNA.

Dr Kari Stefansson, chief executive of deCODE Genetics, who led the research said that most of these mutations were probably neutral - in other words they would have no effect on the carrier.

However, disorders that are thought to result from mutations in several genes, such as autism and schizophrenia, have been shown to be particularly susceptible to the father's age. Because more genes are expressed in the brain than in any other organ, it makes sense that an increase in the number of new mutations is more likely to affect its function.

Dr Stefansson's research confirms this: 'Occasionally, [new mutations] will be deleterious, they will lead to a disease. Once in a blue moon, you will get a mutation that confers a selective advantage. We showed that some of these mutations are in genes that have been indicated in diseases like autism and schizophrenia'.

The research suggests that whereas a 20-year-old father passes on approximately 25 new mutations to a child, a 40-year-old father passes on 65. This means that with every additional year, the father passes on an average of two extra new mutations. In comparison, the authors found that the number of new mutations passed on by the mother is always around 15 regardless of her age.

Professor Richard Sharpe, a specialist in male reproductive health at the University of Edinburgh said the explanation for this was very simple. New mutations only occur when cells copy their DNA to multiply in number. So because men renew their sperm cells continually into old age, they will pick up more mutations over time. Meanwhile, women are born with their eggs and they do not go through further replication.

'[Older father's] sperm will have acquired more mutations than when they were younger, which will increase the chance of children they father inheriting a disease-producing mutation. The risk is small, but it is increased proportionately with the father's age at conception', suggests Professor Sharpe.

Dr Stefansson and colleagues studied the entire genomes of 78 Icelandic parents and their children. From this they were able to show a direct correlation between the number of new mutations in a child's DNA and the age of the father.

Dr Allan Pacey, chairman of the British Fertility Society said that information like this is important to understand, and men and women should not delay parenthood if they are in a position not to.

Autism risk for children with older fathers
Independent |  22 August 2012
Genetics: The rate of human mutation
Nature |  22 August 2012
Kids Of Older Fathers Likelier To Have Genetic Ailments
Shots (NPR health blog) |  22 August 2012
Older dads linked to rise in genetic illness
BBC News |  22 August 2012
Older fathers pass on more genetic mutations, study shows
Guardian |  22 August 2012
Rate of de novo mutations and the importance of father’s age to disease risk
Nature |  22 August 2012
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