The study showed that clonal testes mosaicism promotes the transmission of a pathogenic exon variant to offspring in one of 15 cases and, due to its stability, poses a lifelong threat to children.
As human cells age, mutations accumulate, leading to genetic mosaicism, that is, diversity at the cellular level. This condition occurs in almost everyone, but if the number of abnormal cells exceeds the number of normal cells, chromosomal diseases may develop: for example, Down, Klinefelter, Shereshevsky - Turner and Edwards syndromes have a mosaic form. One part of the cells carries the usual set of chromosomes, and the second one is defective.
It is known that such mutations affect not only their carrier, but also the offspring. Scientists from the Radi Children's Institute of Genomic Medicine and the University of California, San Diego (USA) have studied the patterns of clonal mosaicism in the male gonads, where sperm are formed. The results of the work were published in the journal Cell.
Thanks to 300-fold genome-wide sequencing of blood, saliva and sperm of healthy men, the researchers found that an ejaculate sample carries an average of 33.3 (± 12, 1) variants, and one out of 15 representatives of the so-called stronger sex can transmit mutations to their children. It was in the gonads that clonal mosaicism did not change with age, while in saliva and blood, most mutations were completely absent.
“Earlier studies showed that mutations in sperm cells contribute to disorders such as autism and epilepsy, but the consequences for men without a family history of the disease remained unknown,” said one of the authors of the work, Dr. Joseph Gleeson.
Autism spectrum disorder (ASD) is a developmental disorder in which people have difficulty communicating and behaving. Doctors identify several of its conditions, including autism and Asperger's syndrome; signs can range from mild to severe. The diagnosis is usually made by the age of two - after the children show symptoms such as poor eye contact, not responding to their name, and performing repetitive movements. In boys, ASD is four times more common.
Despite decades of research, the exact reasons for the development of this group of diseases have not yet been clarified: both genetic factors and environmental factors play a role. The authors of the new study confirmed that mutations in male germ cells are also at increased risk for autism spectrum disorder, which can be responsible for 10 to 30 percent of ASD cases.
“Surprisingly, comparisons between older and younger men showed little difference in mutations. Plus, they went unnoticed until children were born,”added Martin Brouss, lead author of the work. Mutations also did not differ in number: from this, scientists concluded that children have a "stable risk" of the disease. In addition, clonal mosaicism can lead to poor pregnancy outcomes in one in 300 cases.
In the future, scientists want to focus on the causes of mutations in the gonads and environmental factors. Researchers are also collaborating with fertility clinics to assess whether the end result is the ability to prevent disease while still in the embryo.