Older fathers' sperm have more mutations--as do their children.
Image: V. Peñafiel/Flickr/GETTY
-
The Best Science Writing Online 2012
Showcasing more than fifty of the most provocative, original, and significant online essays from 2011, The Best Science Writing Online 2012 will change the way...
Read More »
From Nature magazine
In the 1930s, the pioneering geneticist J. B. S. Haldane noticed a peculiar inheritance pattern in families with long histories of haemophilia. The faulty mutation responsible for the blood-clotting disorder tended to arise on the X chromosomes that fathers passed to their daughters, rather than on those that mothers passed down. Haldane subsequently proposed1 that children inherit more mutations from their fathers than their mothers, although he acknowledged that “it is difficult to see how this could be proved or disproved for many years to come”.
That year has finally arrived: whole-genome sequencing of dozens of Icelandic families has at last provided the evidence that eluded Haldane. Moreover, a study published in Nature findsthat the age at which a father sires children determines how many mutations those offspring inherit2. By starting families in their thirties, forties and beyond, men could be increasing the chances that their children will develop autism, schizophrenia and other diseases often linked to new mutations. “The older we are as fathers, the more likely we will pass on our mutations,” says lead author Kári Stefánsson, chief executive of deCODE Genetics in Reykjavik. “The more mutations we pass on, the more likely that one of them is going to be deleterious.”
Haldane, working years before the structure of DNA was determined, was also correct about why fathers pass on more mutations. Sperm is continually being generated by dividing precursor cells, which acquire new mutations with each division. By contrast, women are born with their lifelong complement of egg cells.
Stefánsson, whose company maintains genetic information on most Icelanders, compared the whole-genome sequences of 78 trios of a mother, father and child. The team searched for mutations in the child that were not present in either parent and that must therefore have arisen spontaneously in the egg, sperm or embryo. The paper reports the largest such study of nuclear families so far.
Fathers passed on nearly four times as many new mutations as mothers: on average, 55 versus 14. The father’s age also accounted for nearly all of the variation in the number of new mutations in a child’s genome, with the number of new mutations being passed on rising exponentially with paternal age. A 36-year-old will pass on twice as many mutations to his child as a man of 20, and a 70-year-old eight times as many, Stefánsson’s team estimates.
The researchers estimate that an Icelandic child born in 2011 will harbour 70 new mutations, compared with 60 for a child born in 1980; the average age of fatherhood rose from 28 to 33 over that time.
Most such mutations are harmless, but Stefánsson’s team identified some that studies have linked to conditions such as autism and schizophrenia. The study does not prove that older fathers are more likely than younger ones to pass on disease-associated or other deleterious genes, but that is the strong implication, Stefánsson and other geneticists say.
Previous studies have shown that a child’s risk of being diagnosed with autism increases with the father’s age. And a trio of papers3–5 published this year identified dozens of new mutations implicated in autism and found that the mutations were four times more likely to originate on the father’s side than the mother’s.
See what we're tweeting about
14 Comments
Add CommentSo have they done the next step with the math to see if this correlates to the rise in autism diagnosis in the United States? We know that the average age of parents is much higher and continues to climb. We know that autism rates are climbing. Time to correlate these numbers now that we have some real data indicating that paternal age matters.
Reply | Report Abuse | Link to thishmmm. Few things come to mind.
Reply | Report Abuse | Link to this1. This does tend to explain why IVF, and other assisted-copulation children seem to be so much more susceptible to autism and other disorders (years working at a fertility clinic tends to bring things like this to visibility.) Because the parents are older and hence pass on more mutations to fewer children which compounds with their own medical problems (beyond aging) to create a broth of mutations.
2. As a species gains more and more control over it's environment, the average age of the species will tend to climb. This then drives more mutations and hence possibly sends evolution into hyper drive (since negatively impacting mutations will generally result in the end of a genetic line). Seems like an easy enough experiment to sort fruit flies into younger and older populations and see which one adapts faster to a new condition (food supply, color, weather, drug resistance, etc...) My guess would be the older population adapts faster, as the article implys.
Authors - I think I'm gonna hate to see it, but please give the results for 18 years old's and under-age people, too. Since your report pointed out age 20 is "better" please post to all what the "optimal age" appears to be. Don't worry we (ok, I) won't be offended.
thanks!
I said all along that it was genetic mutations that are causing the explosion of neurological disorders. Now why all of the sudden is age a factor?there have always been older fathers younger moms through the course of history, its a no brainer. What they should have looked at is the fact that vaccines are known mutagens, since after all in 1986 when the vaccine companies got full immunity from lawsuits is when they really just started to require every vaccine available to maximize profits for the Pharmaceutical companies with hundreds of more vaccines in the works, could you just imagine the neurological disorders to come in the near future. There has never been a study that looks at the effects of all the vaccines which are administered to our children. So every year we are seeing an increase of about 10 % in autism rates, if it continues at this rate we will have an autism rate of about 1 in 6 within 10 years, and I seriously doubt that older fathers account for the autism epidemic, and apparently so do the researchers in this study since at the end of the article they say that "de novo gene mutations are a necessary element of human evolution", maybe they are but what mutations are the vaccines causing is what interests people as myself.
Reply | Report Abuse | Link to thisLucky mutations may ultimately be beneficial for the species but in the short term fewer mutations are desirable for the health of the individual and the welfare of the family and the society as problems like autism and schizophrenia create social and personal stressors and in our society they eat up resources. What would be good would be a change in social conventions and structures to allow 20 year olds to father children and have an extended family in particular and society in general be willing to support these children, while the 20 year olds spend their time learning and achieving, instead of the current mean-spirited individualistic culture.
Reply | Report Abuse | Link to thisWhat a lot of anti-vaccine arm waving.
Reply | Report Abuse | Link to thisIt's not the age of the father relative to the mother that is the issue but the absolute age of the father. As an individual ages there is a greater likelihood that some of their cells have spontaneously mutated. For men this means that a greater number of the sperm they produce are likely to be carrying mutated genes, thus the increased risk of offspring inheriting defective genes.
Your claim that vaccines may cause a child's genome to mutate so that they develop a genetic disorder is frankly ridiculous. At best you may be able to argue that the vaccine triggers a condition for which the child is already genetically predisposed. This would still be consistent with, albeit irrelevant to, the finding of this study. Of course, it would be inconsistent with the findings of many other studies which have found no links between vaccines and conditions which appear in early childhood but you shouldn't let that stop you.
Would death be considered an adverse effect ?
Reply | Report Abuse | Link to thisThe recent death of the researcher who died because he has iron overload while working with a live-attenuated plague vaccine ?
I would like a study that focuses on positive traits. An older father has a chance to pass on more evolved genes, so there could be some advantages as well.
Reply | Report Abuse | Link to thisFor example, if a man was 22 when computers and the internet exploded, and is 37 now, do those 15 years of handling higher technology make him more mentally evolved, and would not that be something that becomes part of his genes?
Reply | Report Abuse | Link to this@Seylan In the genetic sense, people do not evolve based on their experiences. Working on computers for years won't make the genes more or less likely to have computer/internet abilities, and more than cutting off the tails of mice will evolve tailless mice. On the other hand, carrying a cell phone that contains rare earth metals and radiates EMF in your pants pocket could conceivably cause mutations; there are studies being conducted now to determine if this is a risk and how much.
Reply | Report Abuse | Link to thisAmazing researches ...
Reply | Report Abuse | Link to thisNow people can plan their families. Couples are quite often in their thirties these days before they can afford children, twice the age for reproduction centuries ago. Could this be causing an increase in mutations?
Reply | Report Abuse | Link to thisAbraham was very old when Isaac and Ishmael were born to different mothers. Could there still be a very ancient mutation around in both Jews and Arabs?
But any mutation that old has probably been bred out by now, anyway.
"carrying a cell phone that contains rare earth metals and radiates EMF in your pants pocket could conceivably cause mutations"
Reply | Report Abuse | Link to thisSomeone I knew got a bald spot on his scalp right where the phone's aerial touches his head. One thing a person may be able to do to reduce this is look at it scientifically , in both radio waves and ultrasound the waves cause the ferritin in the body to release its' iron. Dr. Jerome Sullivan has always held , we don't need any ferritin , as it is a storage form of iron and obviously not required by the body.
"Ultrasound-mediated release of iron from ferritin."
"Our data suggests that superoxide produced as a result of ultrasonic cavitation acts as a reducing agent, enabling the release of iron from ferritin."
"EMF-cancer link: the ferritin hypothesis"
"When EMF was coapplied with iron overload, lipid
peroxidation was further increased as compared to EMF alone while the increase in antioxidant defenses triggered by the sole iron overload was abolished. These data suggest that EMF exposure may be harmful in young adults by impairing the antioxidant defenses directed at preventing iron-induced oxidative stress"
DangDude...Says who....
Reply | Report Abuse | Link to thisAlso interesting to note that a recent report shows IQs are increase at the rate of 1 percent every three years...
Bob Marley's dad was 60 and his mom 17 when he was born. Bob marley died young of melanoma.
Reply | Report Abuse | Link to this