What causes genetic mutations in children? New factors have been identified

What makes one child genetically different from another? In a recent study, experts examined how ancestry, genetic makeup, and lifestyle choices like smoking influence the rate of new genetic mutations in children.

The team analyzed over 10,000 parent-child trios, using data from the 100,000 Genomes Project. The researchers aimed to uncover how new genetic changes – also known as de novo mutations (DNMs) – form in sperm and egg cells and pass down to offspring.

How do new genetic mutations form?

DNMs are not present in the DNA of either parent and are not inherited. They are fresh mutations that arise in the reproductive cells of parents (sperm and eggs) and get passed on to children.

Sometimes, these changes have no impact. Other times, they can lead to severe genetic disorders.

Parental age, especially the father’s, plays a role in increasing DNMs. Each year that a father ages adds around 1.5 mutations to his child’s genetic makeup.

A mother’s aging adds about 0.4 mutations. But is that all? What else could be stirring the genetic pot?

Subtle ancestry differences in mutations

To find out, the researchers scoured genetic data from 10,557 parent-child trios. They looked for genetic variants present in the child but absent in both parents. This approach allowed them to map nearly 689,000 DNMs. It’s the biggest DNM catalog ever created.

But the sheer size of the dataset wasn’t the only notable feature. The researchers explored a diverse range of ancestries, including European, African, South Asian, and American groups. This diversity helped them detect subtle differences in mutation rates linked to ancestry.

Does ancestry matter?

It turns out, ancestry does matter. African ancestry groups exhibited slightly higher DNM rates than other populations.

On average, children of African ancestry inherited about 67 new DNMs per generation. European, South Asian, and American groups inherited about 64 DNMs.

The gap seems minor, but it is statistically significant. The researchers suggest that genetic and environmental factors tied to ancestry may be at play.

Still, age had a far more pronounced effect than ancestry. A two-year difference in a father’s age at the conception of his child could offset the ancestral differences in DNM rates.

Genetic variants don’t explain mutation

Genetic variations within populations could theoretically affect DNM rates. To investigate, the researchers zoomed in on European-ancestry trios. They searched for single nucleotide polymorphisms (SNPs), which are small genetic changes that might influence mutation rates.

The experts found nothing conclusive. No common genetic variants appeared to affect DNM rates significantly.

“The sheer scale of the 100,000 Genomes Project presented a great opportunity to look into the effects and exposures that explain rates and patterns of DNA changes,” said Dr. Aylwyn Scally from the University of Cambridge.

Smoking affects genetic mutation rates

Does smoking alter the genetic blueprint passed to children? Yes, but the effect is small. The researchers found a slight increase in DNMs among children of parents who smoked.

On average, the increase was about 2% – less than one extra DNM over a parent’s reproductive life.

Still, this slight increase caught the researchers’ attention. They noted that while the effect size was small, it was statistically significant.

“While evolution has done its best to develop mechanisms to protect the DNA we pass on to our offspring, our study has shown that it’s not fully protected from certain exposures,” said Dr. Raheleh Rahbari from the Wellcome Sanger Institute.

Implications for genetic studies

The findings matter for genetic research. Current models assume that mutation rates are the same across populations. But what if they aren’t? What if ancestry subtly shapes mutation rates, as this study suggests?

Adjusting genetic models to account for ancestry and lifestyle factors could refine predictions about rare genetic disorders. It could also help scientists pinpoint mutations that are linked to diseases, leading to more accurate diagnoses.

Reproductive health and genetic mutations

Germ cells – sperm and eggs – guard genetic information. Their mutation rates stay low and minimize the risk of transmitting harmful changes. But factors like age, ancestry, and smoking can still nudge those rates higher.

“Ancestry and lifestyle choices like smoking are associated with the number of new DNA changes that arise in the genome,” stated Dr. Hilary Martin from the Wellcome Sanger Institute.

“The effects are small, but they deepen our understanding of genetic variation.”

Further research is needed

Despite its scale, the study had limits. The number of participants from certain ancestry groups was relatively small. And while the researchers examined smoking, they did not explore other potential environmental factors, such as alcohol use or pollutants.

Future studies with larger, more diverse datasets could reveal additional influences on mutation rates. As genetic sequencing becomes cheaper and faster, the ability to track DNMs across generations will most certainly improve.

The study is published in the journal Nature Communications.

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