Tuesday, August 06, 2013

The perils of ageing fathers

A post "Paternal Age" published a little while ago over at West Hunter.
"Decode Genetics has a new report out in Nature that shows how mutations increase with age, by sequencing family trios. They found that women contribute about 15 de novo mutations, independent of age.

"Men contribute more (55 on average) , and the number increases rapidly with age. They found that the average 20-year old father passed on 25 mutations, while the average 40-year old passed on 65, an increase of about two mutations per year of paternal age.
To be precise: if you are a woman and you have a child with a husband aged 28, your infant will on average have 15 + 41 = 56 mutations. Wait another ten years and your unfortunate baby will be 76 mutations worse off. These mutations are unlikely to be good news for your new offspring.
"The researchers talked about the problems caused by these de novo mutations – things like schizophrenia and autism. We already knew that such risks increased with paternal age, but this work quantifies the mutations responsible. 

"Stefánsson opines that the higher mutation rate with older fathers is not that worrisome, since the absolute risk for schizophrenia and/or autism is still small (~2%) and since mutations are our friends: “You could argue what is bad for the next generation is good for the future of our species.
A piece of very sloppy thinking. It's true that mutations generating a very deformed worm, for example, might have ended up as pre-adaptations for limbs and a great future for ambulatory critters (not a great consolation to the ancestral worms if they valued wriggling but sadly went extinct).

Humanity's unique selling proposition is intelligence, a bio-engineered function depending on the exquisite coordination of thousands of genes. You can get more intelligence by mutations (we are, after all, smarter than monkeys) but you need pretty hard selection (i.e. lots of pre-reproductive deaths) to eliminate the overwhelming majority of useless/deleterious genetic changes.

Greg Cochran continues
"Well, not for the first time Kari Stefánsson is wrong. If mutations with large effects are more common with increased paternal age, mutations with small effects must also be more common. Those small-effect mutations are removed slowly by natural selection, and so they accumulate with time. This eventually results in a population in which everyone has a higher genetic load, not just a few unfortunate kids out of each generation.

"... more genes are expressed in the brain than in any other organ, meaning that the fraction of new mutations that will affect its functions is the highest.

"So, what is the likely consequence of a higher paternal age? Population B will eventually be significantly dumber and crazier than population A."
In a small and statistical way, that fate also applies to the children of ageing fathers today.