Disease-causing sperm mutations identified in one in 15 men

A recent study has found that as many as one in 15 men carry mutations in their sperm that could impact the health of their children.

Previous research has reported that children born to older men have a higher risk of being born with some conditions, including autism spectrum disorder (ASD). Researchers from the Rady Children's Institute of Genomic Medicine in San Diego, California and the University of California San Diego School of Medicine used whole genome sequencing to determine whether there are any differences in the number of mutations seen in sperm from older men compared with younger men.

'We found that each ejaculate from a man shows an average of 30 mutations,' said co-first author Dr Xiaoxu Yang. 'Almost all of these were found in serial sampling from a period of six to 12 months, whereas most of the mutations were completely absent from a saliva or blood sample.'

Their results, published in Cell, showed that the number of mutations in the semen samples did not, in fact, differ between younger and older men - although the number of mutations in blood samples (reflecting the somatic genome) did increase with age as expected. Further still, the mutations seen were largely unique to the sperm samples, and were not seen in the saliva or blood of the men tested.

Together, this led the researchers to suggest that the mutations seen in the semen samples had not arisen due to age, but instead had been present since birth and had specifically developed in the sperm cells during embryonic development.

Although the mutations were only seen in a small sub-population of the semen samples – a term called clonal mosaicism – the researchers have speculated that they could give rise to diseases in 1 in 300 conceptions.

Senior author Professor Joseph Gleeson said, 'We think that these mutations contribute a substantial burden on human health, potentially causing 15 percent of ASD cases, congenital heart disease and severe paediatric diseases. But we are hopeful that by identifying men at risk, future cases of disease can be avoided.'

The researchers are now working with fertility clinics to assess whether these mosaic mutations are actually passed to embryos, with the goal of ultimately preventing disease in children.