And how’d that work out for them …. ?

A doubling of risk when the actual risk is 0.2% for the young, and 0.4% for the old, is a considerably different consideration than it is if the actual risk is 20% for the young and 40% for the old.

If there is an overwhelming likelihood of no problem in both cases (and most new mutations have no observable phenotype effect of any kind), the obsessing over paternal age may not make sense. On the other hand, if the increased likelihood of new mutations translates into a sufficiently high actual risk for a particular father in a given birth in an absolute sense, when maybe it wouldn’t have before, then it is worth caring about.

To the extent that conditions like psychosis (bipolar and schizophrenia mostly) and autism spectrum disorders are mostly products of high mutational loads in general, as opposed to mutations in particular genes — in other words, if these conditions are to genetic anomalies what fevers are to infections, a common generalized symptom with an infinite number of particular causes — then genetic testing to determine mutational load at around high school age may make a lot of sense.

The importance of advanced paternal age is much greater for people who already have a high mutational load than it is for people with low mutational loads when it comes to conditions that seems to be associated with generalized mutational load levels. People who want to act on that information need to know it when they can act on it, i.e. not later than the point at which they reach an age when it could make sense in the larger context to have kids if there was a good reason to start early.

The study also suggests that someone interested in mapping neurodiversity generally would be well advised to focus on samples of children (or better yet, as Razib notes, people who are both children and grandchildren) of advanced paternal age fathers.

@1 I recall recently reading a story on assisted reproduction that indicated that while sperm keeps quite well when frozen and is easily transported, that long term storage of eggs doesn’t work as well. In practice, assisted reproduction industry participations have concluded that egg extraction for human assisted reproduction works best when it takes place immediately before the egg is fertilized and happens at the same location where the eggs is fertilized. Egg donors are typically flown in to the place where the extraction and fertilization will take place rather than at a location convenient to them, and then the fertilized egg is transported to whereever it is convenient for the gestational mother. Fertilized eggs are apparently much more amenable to storage and transportation prior to implantation in womb, than unfertilized eggs.

On the other hand, given that genetic defects are much more closely tied to age for sperm (which are produced anew regularly) than for eggs (which are produced early in life and then sit around waiting to be dispensed in a woman’s body), this inbalance may be tolerable.

Another implication of the difference in when sperm v. eggs are created by the body is that men are much more vulnerable to passing on germline viruses and to having pre-conception environmental effects influence their children than women. Women are mostly vulnerable to environmental effects that impact their children while they are pregnant, not before becoming pregnant.

well, i think a molecular biologist would use the term ‘mechanism,’ and make explicit recourse to biophysical processes (e.g., DNA mismatch repair, etc.). to me ‘de novo mutation’ is an abstract phenomena, with contextual, not mechanistic relevance (we’re usually talking about germline). in any case, sperm replicates a lot over your life. so DNA repair is imperfect, and therefore…. that’s the mechanism you’re thinking about.

There are lots of explanations of why paternal age could have a correlation. How much weight should we put on the particular mechanism of de novo mutations?

IIRC, delayed paternal age was a feature of Australian Aborigine societies until recently, where societies were organized into male age bands, with the oldest male band getting the pickings of the youngest women.

I suppose my only point was there have been at least some cultures in which delayed paternal age was the norm for hundreds of years, and yet there doesn’t appear to be some culture-wide loss of fitness as a result. Obviously we shouldn’t expect detailed birth statistics for a population where literacy itself was probably limited to the upper social strata.

Good point, unless some specific types of mutations are more common in older males offspring

A little quick and dirty math suggests that 2 generations of 20 year old fathers would gain us 40+40 de novo mutations, and 1 generation of a 40 year old father would gain us 80. A wash.

@7 Karl: Given that the Greeks practiced infanticide, had extremely high infant mortality, were frequently (usually?) illiterate, kept few/no surviving systematic records, etc., I have no idea why you would expect Greek info to be at all useful on this topic.

@10 Patrick: Random mutations are rarely worth keeping, especially when compared against narrowly tailored specific engineered ‘mutations’ as we may be able to do in the future. (Here, let me shoot a bullet into a random spot in your brain – after all, it might kill a tumor!)

My paternal grandfather was 57 yo when my father was born, my father was 35 yowhen I was born.
My maternal grandfather was 35 when my mother was born.

I was 48 yo when my most recent daughter was born. However when NYU Hospital enrolled me in a 5-year study of advanced parental age, where they took an embryonic sample and tested for 120 known micro-insertions and micro-deletions and 90 other known conditions. They told me to expect 2 or 3 positives, due to my age. When the results came back, they were negative for everything.

My second youngest does have some Autism or Asperger symptoms, but they are abating – he also has very advanced vocabulary. My youngest is very advanced for her age, ans seems like she is going to be even smarter than her older academically gifted sister (9 yo).

So, I’ve either dodged a bullet or there are other unknown low-level stuff lurking out there, that will manifest later?!

#This line of reasoning might be specious. It assumes a lot of things too, which need to be clarified like what ‘an idiot with money’ translates to in a formal sense in the animal kingdom. I assume you mean relatively unfit male with a lot of resources for child rearing, since I am not sure what ‘idiot’ would mean in a non-anthropocentric sense. Why would non-idiots with money be maladaptive for the females? It’s not entirely obvious to me. Maybe someone can explain. In the case of Songbirds, it’s been argued through genetic testing of offsprings that the females cheat on the ‘unfit’ partners by mating with the fitter males in the neighborhood but leaving the child rearing duties to the ‘idiot’ male.