The second is that the effects of parental age on mutation rates differ considerably among families -- much more than had been previously appreciated. In one family, a child may have two additional mutations compared to a sibling born when their parents were ten years younger. Two siblings born ten years apart to a different set of parents may vary by more than 30 mutations.
The result is we are all likely to mutate. At birth, children typically have 70 new genetic mutations compared to their parents - out of the 6 billion letters that make both parental copies of DNA sequence. The new insights were found by performing whole genome sequencing and genetic analysis on 603 individuals from 33 three-generation families from Utah, the largest study of its kind. The families were part of the Centre d'Etude du Polymorphisme Humain (CEPH) consortium that were central to many key investigations that formed a modern understanding of human genetics. The large size of the Utah CEPH families, which had as many as 16 children over a span of 27 years, made them well-suited for this new investigation.
A new study published in eLife seeks to show why some people are born with twice as many mutations as others, and why that characteristic runs in families.
"This shows that we as parents are not all equal in this regard," said Aaron Quinlan, PhD, professor of human genetics at University of Utah and senior author of the study. "Some of us pass on more mutations than others and this is an important source of genetic novelty and genetic disease."
Impacts of new mutations depend on where they land in our DNA, and on the passage of time. On occasion the genetic changes cause serious disease, but the majority occur in parts of our genetic code that don't have obvious effects on human health.
And even though new changes make up a small fraction of the overall DNA sequence, they add up with each subsequent generation. Increasing the so-called mutation load could potentially make individuals more susceptible to illness, said Sasani. It remains to be determined whether factors that impact the mutation rate increase the likelihood for certain diseases.
Although the majority of new mutations originally arise in fathers' sperm, 20 percent of mutations come from mothers' eggs, and increasing age does not drive as many new mutations in moms as it does in dads. Further, it's estimated that one in ten new mutations seen in children come from neither parent. Instead, they arise anew in the embryo soon after fertilization.
Since Utah CEPH families are similar in many ways, all of European ancestry, live within the same geographic region, and likely have similar lifestyles and environmental exposures, since they have a large range in the number of mutations they accumulate, Quinlan hypothesizes that "variability in mutation rates worldwide must be much, much larger."