A large-scale genetic study has revealed that parental age, ancestry, and lifestyle factors like smoking can subtly affect the number and types of new genetic mutations passed from parents to their children. These findings, published in Nature Communications, provide new insights into how both inherited and environmental factors shape human genetic diversity and the risk of certain diseases.
What Are De Novo Mutations?
De novo mutations (DNMs) are genetic changes that occur spontaneously in the egg or sperm and are not present in the parents’ own DNA. These mutations are a key source of genetic diversity in humans, making each person unique. However, some DNMs can lead to developmental disorders or rare genetic diseases.
The Study: Analyzing 10,000 Families
Researchers from the Wellcome Sanger Institute and the University of Cambridge analyzed whole-genome data from over 10,000 parent-child trios as part of the 100,000 Genomes Project. This is one of the largest studies of its kind, cataloguing nearly 689,000 DNMs to better understand what influences their rate and pattern.
Key Findings
– Parental Age Is the Biggest Factor: The age of the parents, especially the father, has the largest impact on the number of DNMs a child inherits. Each year of paternal age adds about 1.5 new mutations, while each year of maternal age adds about 0.4.
– Ancestry Makes a Small Difference: Children of African ancestry had about 3–4% more DNMs than those of European, South Asian, or American ancestry, even after accounting for parental age and other factors. There were also subtle differences in the types of mutations between ancestry groups.
– Smoking Increases Mutation Rates: Parents who smoked were found to pass on about 2% more DNMs to their children. This effect was seen in both mothers and fathers. However, smoking did not explain the ancestry-related differences in mutation rates.
– Other Environmental Factors: The study looked for links between other environmental exposures (like diet or chemicals) and mutation rates but found no consistent effects, except that a later age at menopause in mothers was linked to fewer DNMs.
Why Do These Differences Matter?
Most DNMs are harmless or have only mild effects, but a small number can cause serious genetic disorders. Understanding what influences mutation rates helps scientists predict the risk of such conditions and provides clues about human evolution and diversity.
The finding that ancestry and lifestyle can influence mutation rates challenges the long-held assumption that these rates are uniform across all populations. It also highlights the importance of including diverse populations in genetic studies to get a complete picture of human genetics.
What’s Next?
The researchers emphasize that while the effects of ancestry and smoking are modest, they are real and measurable. They call for future studies with even larger and more diverse datasets, as well as more detailed information on environmental exposures, to uncover additional factors that might influence DNMs.
“Whilst 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. Aylwyn Scally, co-senior author at the University of Cambridge.
This landmark study shows that while parental age remains the main driver of new genetic mutations in children, both ancestry and lifestyle choices like smoking also play a role. These findings deepen our understanding of human genetics and could help inform future research into genetic diseases and evolution.
