Toward healthier gestations

By Razib Khan | July 10, 2012 7:44 pm

Neuroskeptic has a post up, The Coming Age of Fetal Genomics:

So they don’t. Instead, they buy a $100 test kit, they each provide a small blood sample and send it off to one of the companies offering fetal genome testing. At the testing lab, they can separate out the mother’s DNA from that of the fetus, both of which are present in the mother’s blood. By comparing the fetal genome to the mother’s and father’s, it’s easy to spot de novo mutations. If a certain gene doesn’t match either the mother or the father’s sequence, it’s mutated.

A few days later the results are back. There are several mismatches detected. Most are benign – they’re not predicted to have any biological effects. But there’s one, a deletion of a few thousand bases in a gene involved in brain development. This deletion is predicted to raise the risk of epilepsy and autism from 1% to 10% apiece. The parents now have a decision to make. The mutation is a one off, it’s not inherited. If they conceive again… roll the dice again… and it’ll be gone. Do they terminate?

Like the adverts say, “Some people disagree with this, but we say there’s only one person who really matters: your baby.”


Probably not too surprising to readers of this weblog. Years ago I joked that Armand Leroi was a “demon geneticist” for broaching the topic of neo-eugenics. At this point his article isn’t really timely, it’s almost passé! Recently on Facebook an evangelical Christian friend from high school posted a photo of a child with Down Syndrome, making the case for the value of such a life. We’re beyond thought experiment stage, CVS and some of the non-invasive methods are “online.” If Armand was a dark creature, we live in the age of Gog and Magog already. The media just isn’t reporting it for whatever reason.

But I’m not here to scare you. Rather, there is a positive and ethically uncontroversial method by which we can reduce the expected mutational load of any future fetus for a wide swath of Americans. This applies particularly to people who are the core audience of this weblog. Not only am I going to put a proposition out here, but I considered the cost vs. benefit for myself (ultimately, I decided that it wasn’t worth it for various reasons). Let me go to the section of the post which highlights what I’m getting at:

….new mutations, out of the blue, they can affect any family. A clear family history is no protection. They don’t discriminate by race or lifestyle. It’s just the luck of the draw – except that older parents are at much higher risk, especially older fathers. In the case of our couple, she’s 28 and he’s 32. Perfectly normal for this day and age – but very old in biological terms. Humans evolved to be grandparents by 32, not parents….

Sperm are replicated throughout your life. There’s a hypothesis that it is through the male germline that genetic load tends to creep into the population (or, more positively, mutations which ultimately may be the source of variation which drives evolution). Circumstantial evidence implies the children of older males may have decreased quality of life (e.g., higher rates of cancer). I recently asked a researcher who has looked into the question of genetic load in humans, and he seems to lean toward the proposition that sperm quality does decrease as a linear function beyond one’s early 20s. If you are a forward thinking person I assume you’ll already have anticipated me: massive banking of the sperm of young men may result in greatly reduced later life aggregate morbidity on the social scale.

Obviously some of the same applies to eggs, but that’s a more difficult and expensive procedure. And, the storage conditions have to be optimal. But I don’t see this as an insurmountable engineering problem. You should extend this to pre-implantation genetic diagnosis as well, take the zygote(s) with the lowest mutational load values and implant them. But that would be more controversial, due to the expense and the ethics.

I began thinking of this only a year or two back when I was going about starting a family, relatively late in life. Since I’m already “in the game,” and I can’t go back into the past to get my young sperm, I didn’t do this. And long term storage isn’t available in all locales. But if you are a young man who lives in a large urban area and has a decent disposable income, why not? Your symmetrical children with low mutational load will thank you for it.

CATEGORIZED UNDER: Culture, Personal Genomics
  • Whimsy

    Actually, the latest research shows that older fathers may actually pass on the tendency to inherit longer telomeres to their offspring: http://www.pnas.org/content/early/2012/06/05/1202092109.abstract – which pretty much throws out your speculation about the inevitable low quality sperm DNA of older fathers.

  • https://plus.google.com/109962494182694679780/posts Razib Khan

    #1, i’m aware of that research. you don’t think it’s retarded to rely on one published paper to overturn your prior beliefs in biomedical science? also, it’s not just speculation. there are papers going in the other direction too. you’re educated enough to know that if you are who i think you are.

    i’d appreciate it if future commentary was a little less stupid than #1. i actually considered adding an addendum addresing the telomere paper to head off this sort of comment, since i noticed a lot of people were really excited by the publication on the interwebs. so i’ll do so in the future, as i can’t assume that the readers won’t jump in in such an immature manner.

  • Karl Zimmerman

    Is there any evidence that children conceived using frozen sperm have higher mutation counts after controlling for other factors? Frozen ovum are less viable than fresh ones, although after a certain maternal age, the overall viability for a younger woman’s frozen eggs is greater.

    Still, I would assume even if the freezing process made a certain percentage of sperm nonviable, the percentage which were still viable enough to penetrate the ovum would have minimal damage to their DNA. But I know next-to-nothing about how the freezing process can damage DNA, so feel free to school me.

  • https://plus.google.com/109962494182694679780/posts Razib Khan

    #3, i too am a student of this. perhaps my friends from alcor might weigh in….i’ll point this to ‘em

  • marcel

    In the case of our couple, she’s 28 and he’s 32. Perfectly normal for this day and age – but very old in biological terms. Humans evolved to be grandparents by 32, not parents….

    Is it really the case that “Humans evolved to be grandparents by 32, not parents”?

    I can imagine that this is the case for females, but my inexpert impression of the literature on humans in hunter-gatherer societies and of monkeys and apes is that young adult males[1] are pretty low in the male dominance hierarchy and likely do not get many mating opportunities; mating opportunities tend to be restricted to higher ranking males who are, in turn, usually older. I would think that among humans, males evolved to be grandparents by late 30s or 40s (if they survived that long).

    [1] 15 year old males ~ young adult males.

  • https://plus.google.com/109962494182694679780/posts Razib Khan

    #5, i had the same question. i assume it’s bloggerary license?

  • jb

    A question: Given that the children of older men have higher mutational loads, I would assume it would follow that their grandchildren would inherit those mutational loads, even if those grandchildren were conceived while their parents were young. Is this correct?

    I ask because if this is so, it would seem to follow that the practice of delaying children could lead fairly quickly to a general — and not easily reversible — genetic deterioration of a population. If an effect is detectable after only one generation, what might it look like after five generations where half of a population has delayed childbearing into the late 30’s or early 40’s, and where medical advances have preserved the functionality of people who in earlier times would either have died, or at least been rendered unmarriageable. What I’d like to know is whether you see this as actually being a problem, and if so how serious.

    (Actually, even without delayed childbearing, I’m wondering how mutational load gets cleared from a population where advanced medicine guarantees that almost everybody can reproduce if they choose to, and where the number of children people have is unrelated to their genetic fitness).

  • https://plus.google.com/109962494182694679780/posts Razib Khan

    I’m wondering how mutational load gets cleared from a population where advanced medicine guarantees that almost everybody can reproduce if they choose to, and where the number of children people have is unrelated to their genetic fitness

    miscarriage rates will probably increase, resulting in a “floor” on the load.

  • marcel

    i assume it’s bloggerary license

    Um, I guess, if you say so. I hope that science bloggers, esp. those directing themselves at informed but nevertheless lay readers (i.e., not experts in the subject matter at hand), allow themselves very little license.

  • http://www.lagriffedulion.f2s.com/ Paipo Jim

    As for the nurture rather than nature effects of late parenthood, I fathered children at the ripe old age of 37 and 39. My father was 39 when I was born and his father was 38 when he was. The only discernible effect it has had on my 20-something children is that they have a somewhat “old-fashioned” perspective on societal mores (and an exposure to if not an appreciation of music from The Great American Songbook.) This is all to the good as far as I’m concerned.

  • April Brown

    #3 – For what it’s worth, I ran the question about frozen sperm by an IVF specialist recently. She indicated that it was an all or nothing sort of situation with sperm. Either it’s damaged by freezing (in which case it’s obvious and not used) or it’s not. Since she uses a process called.. ICSI? Something like that, where she picks a sperm and injects it directly into the egg (instead of the free for all under more natural circumstances) I gather she’s able to select better quality sperm.

    I don’t know what her sources were, but she is a very well respected IVF doctor in the DC area with a good track record, so that would seem to hold some weight.

  • http://backseatdriving.blogspot.com/ Brian Schmidt

    Average age at menopause might be a better determinant of the genetically optimal time for women to start transitioning to non-maternal roles under natural conditions (whatever that was), rather than a theoretical first opportunity to be a grandmother.

  • Ria

    #12, no, perimenopause begins up to 10-15 years prior to the beginning of menopause and is marked not only by declining fertility, but by increased (dramatically increased) rates of a variety of birth defects and chromosomal abnormalities, difficulty pregnancies, high-risk pregnancies, etc. Early to mid 30s is not unreasonable as an age to anticipate women being genetically optimized for initial transition to grandmotherhood. Particularly since our ancestors did not always have the medical care and dietary benefits (both overall calorie consumption and vitamin/mineral consumption) that would be so necessary to successful pregnancy, particularly later in life.

    #8, I agree with your comment about the limitations on the mutational load. The impact upon society would be harder to gauge, but I would anticipate a slow and steady decline without sufficient immigration to offset the declining native birth rate. At some point, the immigration rate may exceed the ability of the society to successfully integrate the new immigrants causing substantial changes to the character of the society (for better and for worse, I’m sure, and hard to predict). Nothing you aren’t already familiar with, of course. It would seem that quite a bit of generationally-based unrest could ensue.

  • http://backseatdriving.blogspot.com/ Brian Schmidt

    #13 Ria – reasonable point, the end of the long transition to infertility isn’t the right age to be identified as the time it first becomes optimal to be infertile. On the other hand, the beginning of the long transition also isn’t the right place.

    Maybe the long transition itself allows for difference in human experience as to what’s optimal.

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Gene Expression

This blog is about evolution, genetics, genomics and their interstices. Please beware that comments are aggressively moderated. Uncivil or churlish comments will likely get you banned immediately, so make any contribution count!

About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at http://www.razib.com

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