Mutations in sperm of older men can pass health disorders onto their children, study finds

Mutations in the sperm of older men can be passed down to their children and cause health disorders, such as heart disease or autism, a new study suggests.

Researchers from the Rady Children’s Institute of Genomic Medicine and University of California San Diego School of Medicine found that 1 in 15 men, notably older men, are more at risk from passing on negative mutations to their children than younger men.

The mutation of the cells, known as mosaicism (where different cells in the same person have different genetic makeup), occurs in almost everyone. However, if abnormal cells outnumber normal cells, disease can occur.  

‘Our earlier studies told us that sperm mutations contribute to the cause of disorders, such as autism and epilepsy, but the implications in men without a family history of disease was completely unknown,’ said study co-author, Dr. Joseph Gleeson, in a statement. 

Autism spectrum disorder (ASD) is a developmental disorder in which sufferers have a hard time communicating and with behavior.

It encompasses several conditions – including autism and Asperger’s syndrome – and symptoms can range from mild to severe.

Children are usually diagnosed by age two after they exhibit signs such as reduced eye contact, not responding to their name and performing repetitive movements.

According to the Centers for Disease Control and Prevention, about one in 59 children has ASD.

Boys are much more likely – up to four times – to have the condition than girls.

Despite decades of research, the causes of ASD remain a mystery. Both genetics and environmental factors are believed to play a role.

However, recent studies have suggested that de novo mutations may be the cause of between 10 and 30 percent of ASD cases.

The study added that with sperm, unlike blood, mosaicism does not change with age.

‘Surprisingly, the comparison between the old and young men showed few differences in mutations, telling us that these mutations probably arose when the father was an embryo, where the mutations could reside undetected until the man has children,’ said the study’s lead author, Dr Martin Breuss. 

The researchers uncovered a new way to observe and count the mutations, while using the data to predict the possible impact on any future offspring.

They also found the mutations did not differ in number, leading the researchers to believe there is a ‘stable risk’ of disease in children. They also found that mutations are likely to happen in single sperm cells, which are presently below levels of detection.

They sequenced multiple samples hundreds of times across their genomes to find that the mutations were only in a small number of cells.

‘We found that each ejaculate from a man shows an average of 30 mutations,’ study co-author, Dr Xiaoxu Yang added. 

‘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.’ The data, said Yang, indicates the mutations are restricted to sperm cells, and also validates their detection method. 

Though concerning, the researchers added that since these sperm cells are in a stem niche, that should limit the chances for the health problems to be passed on.

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

The research was published earlier this week in the scientific journal Cell.