Dr. Kári Stefánsson and his colleagues are looking at how the parents’ age and sex determine new genetic mutations in the offspring.
Characteristics that we inherit from our parents – starting with very basic features such as eye color or hair texture – shape not just our identity, but also the state of our health, both earlier and later in life.
That being the case, the study of genetics has become central to understanding who and what we are, as well as how our bodies are likely to develop in time, and how we might respond to internal or external factors.
Given the importance of understanding the role of genetic factors to our health profile, scientists are constantly striving to decipher the mysteries of the human genome.
A new study conducted by researchers at deCODE genetics in Reykjavik, Iceland, has revealed that the parents’ age at the time of conception influences de novo mutations (DNMs) in children – that is, genetic changes that are seen in the offspring, but not in their parents.
Senior study author Dr. Kári Stefánsson, the chief executive officer of deCODE genetics, told Medical News Today that this research is very important to understanding how and why rare childhood diseases occur.
“Now […] it is clear,” he said, “that DNMs are responsible for a very large percentage of rare diseases of childhood. So it’s extraordinarily important from a clinical point of view to understand the way in which DNMs are generated, to understand whether they are coming from the mother or father, how they are when they come from one but not the other.”
The researchers’ findings were published yesterday in the journal Nature and are available online.
More DNMs are caused by older fathers
Dr. Stefánsson and colleagues analyzed genome data from 14,688 individuals across the general population of Iceland. From these, they focused on 1,548 trios of parents and children. They also analyzed the origin of DNMs across three generations in 225 of the participants.
They sought to map out the interactions between parental sex and age and the type of genetic mutations that occur in the children, as well as the location of these mutations in the genome.
Following the researchers’ analysis, they found that the number of DNMs caused by the mothers increases by 0.37 with each year of age. In the case of DNMs influenced by fathers, their number increases by 1.51 per year, making paternal influence almost four times stronger in this context.
“In this paper,” Dr. Stefánsson explained to us, “we focus very much on the difference between the maternally derived and the paternally derived DNMs and we show that indeed there is a difference in what kind of mutations you’re most likely to get from the mother and father.”
“The total number of genome mutations that come from the father is about four times greater than [that which] comes from the mother,” he added.
However, DNMs caused by the mother are equal in number to DNMs caused by the father in around 10 percent of the genome, the researchers noted. Also, most maternal DNMs in these regions of the genome are C-to-G transversion mutations, leading to genome strand breaks.
This can affect the way in which a gene works, or even whether it works at all, and such mutations can sometimes lead to a risk of developing certain diseases.
Higher mutation rate in genome hotspots
At the same time, the team noted that the increase in the number of clustered gene mutations, or mutations that take place in “hotspots” on the genome, is influenced more by the mother’s age.
It was also found that the “life span” of DNM clusters derived from the mother is longer than that of paternal DNM clusters, and maternal DNMs change a lot more throughout time.
“Ten percent of the genome is vulnerable to double-stranded breaks, therefore this 10 percent of the genome has high density of [C-to-G] mutations coming from the mother, but what does it mean that [in this region] you have basically a mutation rate that is twice the mutation rate elsewhere in the genome?” asked Dr. Stefánsson.
He then went on to explain to MNT that “it means that whatever attribute is conferred on us by genes in this 10 percent of the genome must evolve faster than other attributes, because you have more diversity to select.”
He told us that in the future, taking into account the serious clinical implications of the findings so far, it will be useful to understand whether DNMs to which one child is predisposed might also occur in younger siblings.
“The next chapter of our work is going to answer […] the question that is asked by almost every parent when they are told that [their child’s condition] is caused by de novo mutations. The question is, how likely is it that this mutation is going to show up in a subsequent child?”
Dr. Kári Stefánsson