Fathers Pass On 4 Times As Many New Genetic Mutations As Mothers

Fathers Pass On 4 Times As Many New Genetic Mutations As Mothers.

Children inherit four times as many new mutations from their fathers than their mothers, according to research that suggests faults in the men’s DNA are a driver for rare childhood diseases. Researchers studied 14,000 Icelanders and found that men passed on one new mutation for every eight months of age, compared with women who passed on a new mutation for every three years of age. The figures mean that a child born to 30-year-old parents would, on average, inherit 11 new mutations from the mother, but 45 from the father. Kari Stefansson, a researcher at the Icelandic genetics company, deCODE, which led the study, said that while new mutations led to variation in the human genome, which is necessary for evolution to happen, “they are also believed to be responsible for the majority of cases of rare diseases in childhood.”

Scientists know from previous research that children born to older fathers have a greater risk of developing certain disorders, including intellectual disabilities, autism and schizophrenia. New mutations are a likely factor, given that more genes are active in the brain than in any other organ in the body. Children inherit new mutations when they build up in the father’s sperm and the mother’s eggs. Men pass on more mutations than women because they make sperm throughout their lives, using a process that is not perfect at copying DNA. And so, as the man ages, his sperm accumulate more and more mutations. Women pass on fewer mutations because they tend to be born with their full complement of eggs.

In the study published in Nature, the researchers analysed the DNA of 1,500 Icelanders and their parents and, for 225 people, at least one of their children. They found that new mutations from mothers increased by 0.37 per year of age, a quarter of the rate found in men. While the vast majority of new mutations are thought to be harmless, occasionally they can disrupt the workings of genes that are important for good health. The scientists also found that in some parts of the genome, new mutations were overwhelmingly passed on from mothers. In one section of chromosome 8, for example, the researchers found 50 times more mutations from the mother than in any other part of the genome. The scientists speculate that the cluster of mutations reveals an ancient Achilles heel in the genome: a region where the chromosome can easily break in two, but can be patched up, leaving mutations as a genetic scar. “It seems that when a chromosome breaks in an egg, it can sometimes be repaired, avoiding a chromosomal catastrophe but leaving a scar of small mutations,” said Martin Taylor, a geneticist at the University of Edinburgh.

Allan Pacey, professor of andrology at Sheffield University, said: “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. Put simply, the genetic quality of sperm from younger men, in terms of new mutations, is generally much better than that of older men.”

Credit: Ian Sample for The Guardian 20 September 2017.