De novo mutation explained

A de novo mutation (DNM) is any mutation or alteration in the genome of an individual organism (human, animal, plant, microbe, etc.) that was not inherited from its parents. This type of mutation spontaneously occurs during the process of DNA replication during cell division. De novo mutations, by definition, are present in the affected individual but absent from both biological parents' genomes. These mutations can occur in any cell of the offspring, but those in the germ line (eggs or sperm) can be passed on to the next generation.^[1]

In most cases, such a mutation has little or no effect on the affected organism due to the redundancy and robustness of the genetic code. However, in rare cases, it can have notable and serious effects on overall health, physical appearance, and other traits. Disorders that most commonly involve de novo mutations include cri-du-chat syndrome, 1p36 deletion syndrome, genetic cancer syndromes, and certain forms of autism, among others.^[2]

Rate

The rate at which de novo mutations occur is not static and can vary among different organisms and even among individuals. In humans, the average number of spontaneous mutations (not present in the parents) an infant has in its genome is approximately 43.86 DNMs.^[3]

Various factors can influence this rate. For instance, a study in September 2019 by the University of Utah Health revealed that certain families have a higher spontaneous mutation rate than average. This finding indicates that the rate of de novo mutation can have a hereditary component, suggesting that it may "run in the family".^[4]

Additionally, the age of parents, particularly the paternal age, can significantly impact the rate of de novo mutations. Older parents, especially fathers, tend to have a higher risk of having children with de novo mutations due to the higher number of cell divisions in the male germ line as men age.^[5]

In genetic counselling, parents are often told that after having a first child with a condition caused by a de novo mutation the risk of a having a second child with the same mutation is 1 – 2%. However, this does not reflect the variation in risk among different families due to genetic mosaicism. A personalised risk assessment can now quantify people's risk, and found that the risk for most people is less than 1 in 1000.^{[6] [7]}

Role in evolution

De novo mutations play a crucial role in evolution by providing new genetic variation upon which natural selection can act. They serve as a primary source of genetic diversity, enabling species to adapt to changing environments over time.^[8]

Origin of the term

This comes from two Latin words:

• de, in this case meaning "from";
• novo, in this case the neuter ablative singular of novus, "new".

Notes and References

1. Veltman . Joris A. . Brunner . Han G. . De novo mutations in human genetic disease . Nature Reviews Genetics . 13 . 8 . 565–575 . 10.1038/nrg3241 . 2012 . 22777127. 4110909 .
2. Sanders . Stephan J. . Ercan-Sencicek . Gunes A. . Hus . Varun . Willsey . A. Jeremy . Murtha . Michael T. . Moreno-De-Luca . Daniela . Cho . Judy . Shi . Yunjia . Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism . Neuron . 70 . 5 . 863–885 . 10.1016/j.neuron.2011.05.002 . 2011 . 21658581. 3939065 .
3. Li . Jingjing . Oehlert . John . Snyder . Michael . Stevenson . David K. . Shaw . Gary M. . 2017-04-07 . Fetal de novo mutations and preterm birth . PLOS Genetics . 13 . 4 . e1006689 . 10.1371/journal.pgen.1006689 . 1553-7390 . 5384656 . 28388617 . free .
4. Web site: Some parents pass on more mutations to their children than others . 2022-06-05 . ScienceDaily . en.
5. Rahbari . R. . Wuster . A. . Lindsay . S.J. . Hurst . J.M. . Rahbari . R. . Timing, rates and spectra of human germline mutation . Nature Genetics . 48 . 2 . 126–133 . 10.1038/ng.3469 . 2016 . 26656846. 4731925 .
6. Bernkopf . Marie . Abdullah . Ummi B. . Bush . Stephen J. . Wood . Katherine A. . Ghaffari . Sahar . Giannoulatou . Eleni . Koelling . Nils . Maher . Geoffrey J. . Thibaut . Loïc M. . Williams . Jonathan . Blair . Edward M. . Kelly . Fiona Blanco . Bloss . Angela . Burkitt-Wright . Emma . Canham . Natalie . 2023-02-15 . Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation . Nature Communications . en . 14 . 1 . 853 . 10.1038/s41467-023-36606-w . 2041-1723 . 9932158 . 36792598. 2023NatCo..14..853B .
7. 10 August 2023 . Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation . Nature Communications. 10.1038/s41467-023-36606-w . Bernkopf . Marie . Abdullah . Ummi B. . Bush . Stephen J. . Wood . Katherine A. . Ghaffari . Sahar . Giannoulatou . Eleni . Koelling . Nils . Maher . Geoffrey J. . Thibaut . Loïc M. . Williams . Jonathan . Blair . Edward M. . Kelly . Fiona Blanco . Bloss . Angela . Burkitt-Wright . Emma . Canham . Natalie . Deng . Alexander T. . Dixit . Abhijit . Eason . Jacqueline . Elmslie . Frances . Gardham . Alice . Hay . Eleanor . Holder . Muriel . Homfray . Tessa . Hurst . Jane A. . Johnson . Diana . Jones . Wendy D. . Kini . Usha . Kivuva . Emma . Kumar . Ajith . Lees . Melissa M. . 14 . 1 . 853 . 36792598 . 9932158 . 2023NatCo..14..853B . 1 .
8. Book: Hartl . Daniel L. . Clark . Andrew G. . Principles of Population Genetics . 2007 . Sinauer Associates . 978-0-87893-308-2 . 45–47.