A new paper in Genome Biology and Evolution has found that the relationship between paternal age and rare congenital disorders is more complex than scientists previously thought.
Scientists have long known that older fathers are more likely to have children with bone and heart abnormalities, such as achondroplasia, Apert syndrome, Noonan or neurodevelopmental disorders, schizophrenia, and autism, due to genetic mutations that accumulate in sperm over time. the time.
Recent scientific evidence indicates that the relationship between paternal age and certain genetic changes is more complex than previously thought. The study shows that while paternal age is associated with an increased risk of certain mutations, others can occur even before puberty.
During the recent study, researchers found that delayed parenthood increases the risk of mutations that contribute to the development of congenital diseases in children. The study particularly emphasizes the role of “driver” or “selfish” mutations (genetic parts that can enhance their transmission to future generations at the expense of other genes in the genetic content), which are more prevalent in older men and contribute significantly to congenital disorders.
Delayed parenthood increases the risk of inheriting a new mutation that may cause a congenital disorder in the offspring. In particular, the frequency of some FGFR3 mutations increases with age.
Fibroblast growth factor receptor 3 (FGFR3) is a protein in humans that is expressed in tissues including cartilage, brain, intestine and kidney.
“Driver” or “selfish” mutations that can lead to congenital disorders are more common in the germ line (sequences of germ cells that have genetic material that can be passed down to offspring), and their frequency in aging men is much higher than the estimated average mutation rate. For every cell division, for every generation.
Despite the importance of “selfish” mutations in the male line due to their high incidence and frequency, as well as their pathogenic effects, researchers do not understand where mutations really come from and why they are found so often.
In the study, researchers collected sperm samples from anonymous donors at clinics in Austria and investigated the variable frequency of genetic mutations for 10 different FGFR3 mutations in men aged 23 to 59 years.
The researchers found that the FGFR3 variant associated with achondroplasia, the most common form of dwarfism, increases with paternal age. Another variant, associated with secondary dysplasia, a severe and usually fatal skeletal disorder in children characterized by a disproportionately small rib cage and very short limbs, also increases with the father's age.
However, the researchers found that many FGFR3 mutations were not linked to paternal age. In particular, the variant associated with CATSHL syndrome (acromegaly, tall stature, and hearing loss syndrome) was no more common in sperm of older men compared to younger men.
What would happen to humans if the Y chromosome "vanished"?
The Y chromosome, which contains the male-determining gene in humans and other mammals, is deteriorating in the human race and may disappear after a few million years, scientists report.
Many scientists say this would lead to extinction unless humans evolved a new sex gene.
The sex of the fetus in humans and other mammals is determined by the X and Y genes. Females have two X chromosomes, and males have one X chromosome and a small Y chromosome.
The Y chromosome has a strong influence because it contains a very important gene that initiates male development in the fetus.
All fetuses are female until about week 12, and then the gene on the Y chromosome starts turning on other genes that regulate testicular development (which is why men have nipples).
Professor Jenny Greaves explained the reason behind the “vanishing” of the Y chromosome, saying that during the past 166 million years, the human Y chromosome has lost between 900 and 55 active genes, which means the loss of 5 genes for approximately every million years. At this pace, the last 55 genes in the Y chromosome are expected to disappear in about 11 million years.
This may not seem like an imminent existential crisis, but other scientists argue that the lifespan of the Y chromosome could range from a few thousand years to infinity.
However, humans are not the only species facing a Y chromosome crisis, as two rodent strains have already lost their Y chromosome, yet are still surviving.
These breeds in which the Y chromosome has completely disappeared include mole voles in Eastern Europe and spiny rats in Japan.
Although it is not yet clear how mole rats determine sex without the SRY gene (testis determination factor or sex-determining region Y protein , responsible for initiating male sex determination in humans), they have had luck with spiny rats, a group of three different species. On the Japanese islands, they are all threatened with extinction.
While they discovered that most of the genes on the Y chromosome of spiny rats had been transferred to other chromosomes, it took some time to track down what had replaced SRY.
Scientists have succeeded in determining the DNA sequences found in male mice. After studying the sequence more closely, they discovered a small difference near a gene called SOX9. According to the study, this gene tells the body how to make a protein important for the development of the testicles.
Scientists believe that this extra piece of DNA is like a switch that turns on SOX9, even without the SRY gene.
So what does this mean for humans?
Humans need a female egg and a male sperm to reproduce, and one simply does not work without the other. Which means that the end of the Y chromosome could herald the extinction of the human race.
Professor Greaves said: “The results support an alternative possibility, which is that humans could develop a new sex-determining gene. But it may still not be that simple.”