View Full Version : Father's age at conception influences offspring's mutation rate

13-06-14, 00:29
I saw this on my feed today..."Father's Age Influences Rate of Evolution

The study is about chimpanzees, but there's some good information as to implications for humans as well.

Sorry, the title should read: Father's age influences mutation rate

13-06-14, 02:23
That's right, the older the sperm the more mutations it has. There was a study blaming rising age of modern fathers and mothers for skyrocketing cases of Down syndrome in kids.

13-06-14, 02:56
This caught my eye too...
"Paternal age is an established risk factor in a number of disorders including schizophrenia and autism."

It amazes me how many cases of autism we have nowadays, and I don't think better diagnostic procedures explains it all.

Reminds me of an old proverb I grew up with too...old fathers, feeble children.

13-06-14, 23:24
if this is true then it seems the best strategy for a woman would be to marry an older guy with a good income, play the ignorant conservative devoted wife and have kids with a young lover. Husbands beware... :) she might have genetical reasons for cheating.

13-06-14, 23:43
if this is true then it seems the best strategy for a woman would be to marry an older guy with a good income, play the ignorant conservative devoted wife and have kids with a young lover. Husbands beware... :) she might have genetical reasons for cheating. If the kid is strong and healthy "damn, surely it is not mine!", lol.

14-06-14, 00:41
If the kid is strong and healthy "damn, surely it is not mine!", lol.

And that's why the French ban DNA testing to determine paternity.

14-06-14, 01:29
One way out for older father is to get a young mother. I had a friend about 19 but his father was 80 while is mother was maybe 40. He seemed all right. We were in high school together. His father had four wives and this guy's mother was the fourth wife.

I think most of the R1b mutations could have been that they had multiple wives and were making babies well into old age.:wink:

14-06-14, 16:34
A very old story, gentlemen, and not limited to one country...Joseph and the Pharaoh's wife!


However, maybe we should keep in mind that often in the past, it was not the woman's choice...in this case, the old goat deserved everything he undoubtedly got!


20-08-14, 12:55
I did a study on paternal and maternal age and their correlation with autism.
Increasing parental age is one of the factors implicated in the elevated rates of autism we are finding.

04-09-14, 20:39
This explains a lot my great uncle born when his father was in his forties did need some adaptions, a horse that was a different size from his friends and he could only drive a Jag because of his difficuty in seeing out off it. He didn't even live to 90 only reaching 88 and height wise he only reached 6ft 5inches.

09-09-14, 16:03
More scientific proof linking paternal age with increased mutations. Of course, not all would be deleterious, but my understanding is that most of them would be...

Determinants of Mutation Rate Variation in the Human Germline:

In terms of replication errors...from the paper:
After puberty, sperm are continuously produced through the asymmetric division of self-renewing spermatogonial stem cells every 16 days (61). Five additional cell divisions (corresponding to four replication events) are required to obtain mature sperm. As a consequence, if puberty occurs at 13 years (116), approximately 38 + 23×(30 − 13) = 429 stem cell divisions have occurred if conception takes place at a paternal age of 30 years, and approximately 659 have occurred if conception takes place at a paternal age of 40 years. If mutations are due largely to replication errors, we expect most to be introduced in the paternal germline, at a rate that depends on paternal age. A greater contribution of paternal mutations was first noted in studies of human Mendelian disease (29, 55). This observation was lent strong support by molecular evolution studies of autosomes and X and Y chromosomes that reported lower divergence on the X than on the Y and autosomes (97, 104).

Ovum are also produced throughout life, however, again according to the paper:
In that regard, it is plausible that sequencing more families may yet reveal a maternal age effect on the number of maternal de novo mutations (46). This effect is expected to be subtle compared with the paternal one, however.

This seems to be one of those cases where, perhaps because the linkage between paternal age and "weakness" of offspring was unknown in some cultures, or because power and wealth was more important, societal practices actually worked (and works) against the fitness of the group as a whole.

10-09-14, 21:20
How bizarre...scientific research re-affirming a long established link between paternal age and defects in the offspring seems to have offended someone. I would suggest taking it up with all the scientists, instead of shooting the messenger! :)

10-09-14, 23:10
Yet another new paper on this topic:
New insights on human de novo mutation rate and parental age. W. S. W. Wong, B. Solomon, D. Bodian, D. Thach, R. Iyer, J. Vockley, J. Niederhuber.

Germline mutations have a major role to play in evolution. Much attention has been given to studying the pattern and rate of human mutations using biochemical or phylogenetic methods based on closely related species. Massively parallel sequencing technologies have given scientists the opportunity to study directly measured de novo mutations (DNMs) at an unprecedented scale. Here we report the largest study (to our knowledge) of de novo point mutations in humans, in which we used whole genome deep sequencing (~60x) data from 605 family trios (father, mother and newborn). These trios represent the first group of approximately 2,700 trios who have undergone whole-genome sequencing (WGS) through our pediatric-based WGS research studies. The fathers ages range from 17 to 63 years and the mothers ages range from 17 to 43 years. We identified over 23000 DNMs (~40 per newborn) in the autosomal chromosomes using a customized pipeline and infer that the mutation rate per basepair is around 1.2x10-8 per generation, well within the reported range in previous studies. We were also able to confirm that the total number of DNMs in the newborn was directly proportional to the paternal age (P less than 2x10-16). Maternal age is shown to have a small but significant positive effect on the number of DNMs passed onto the offspring, (P =0.003) , even after accounting for the paternal age. This contradicts the prior dogma that maternal age only has an effect on chromosomal abnormalities related to nondisjunction events. Furthermore, 5% (22 total) of newborns in the analyzed group were conceived with assisted reproductive technologies (ARTs), and these infants have on average 5 more DNMs (Bias corrected and accelerated bootstrap 95% Confidence Interval, 1.24 to 8.00) than those conceived naturally, after controlling for both parents ages. Both parents ages remain significant as independently correlated with DNMs even after the families that used ARTs were removed from the analysis. Our study enhances current knowledge related to the human germline mutational rates.