the researchers of the Rady Children’s Institute of Genomic Medicine and the University of California San Diego School of Medicine found that mutations in the human sperm they can be the cause of various pathologies diagnosed in the offspring.
The study was published in the scientific journal Cell.
Mutations in human sperm: here’s what the research says
During development, life and aging processes, all human cells accumulate mutations, resulting in what is referred to as mosaicism, a condition in which different cells in the same person have different DNA sequences or genetic makeup.
Mosaicism manifests itself in every human being, but it is mostly unnoticeable. If the mutated cells begin to outgrow healthy cells, disease can occur. Once mosaicism occurs in human sperm or egg, mutations can affect either man or woman.
Scientists from the Rady Children’s Institute of Genomic Medicine and the University of California San Diego School of Medicine explained that most likely one in 15 men carry these mutations in their sperm that could negatively affect their offspring.
Previous research has revealed that older men are at a higher risk of causing certain diseases in their children, such as autism spectrum disorder (ASD) and some birth defects. In the latest study, the experts compared sperm from older men to younger men to ascertain any differences in mutations.
After this comparison, the results were significant: detectable mutations did not differ in number, suggesting that these mutations create a stable risk of disease in the offspring. The results also indicated that age-associated mutations appear more likely to arise in individual spermatozoa, occurring below current detection levels.
“Our previous studies have 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 the disease were completely unknown.The senior author said Joseph Gleeson, MD, professor of neuroscience at Rady. UC San Diego School of Medicine and director of neuroscience research at Rady Children’s Institute for Genomic Medicine.
The researchers sequenced human sperm in multiple samples hundreds of times across their entire genomes to track down mutations that occur in only a small percentage of cells, using state-of-the-art machine learning tools.
“We found that every single human sperm shows an average of 30 mutations“Explained the co-first author Xiaoxu Yang, Ph.D., a postdoctoral scholar in Gleeson’s lab. “Almost all of these mutations have been theresionated in serial sampling for a period of six to 12 months, while most of the mutations were completely absent from a saliva or blood sample ”. The data, Yang said, indicate that the mutations are limited to sperm and also validate their method of detection.
“Surprisingly“Said the co-first author Martin Breuss, Ph.D., assistant professor of clinical-pediatric genetics and metabolism at the University of Colorado School of Medicine and former postdoctoral fellow in Gleeson’s lab, “Comparisons between the old and the young showed little difference in the mutations, telling us that these mutations probably originated when the father was an embryo, where the mutations could reside undetected until the man has children.”
Breuss made it clear that it also means that sperm are well protected in a stem cell niche, which does a good job of maintaining stem cell populations and their relative contribution to each human sperm sample.
“We believe that these mutations contribute to a substantial burden on human health “, Gleeson said, “potentially causing 15% of cases of ASD, congenital heart disease and severe pediatric disease. But we hope that by identifying men at risk, future cases of the disease can be avoided ”.
According to the study authors, future research will focus on identifying the causes of mutations that occur in older men and on environmental exposures that could explain the observed increases in mutations. The team is recruiting families where a child has a disease due to a new mutation and where the father can donate a sperm sample to test for evidence of the mutation.
Researchers are also working with infertility clinics to assess whether these mosaic mutations are passed on to embryos, with the goal of ultimately preventing any disease from any offspring.
Mutations in human sperm: this is how the risk of autism can be revealed in future offspring.
To date, the causes of Autism Spectrum Disorder or ASD have not been fully disclosed. Experts believe that both genetics and the environment play a vital role. In some cases, the disorder is linked to mutations de novo which appear only in the child and are not inherited from the DNA of either parent.