The Coming Age of Fetal Genomics

By Neuroskeptic | July 10, 2012 7:57 pm

It’s 2020. A young woman and her partner have just found out that she’s pregnant with her first child. and they’re going to be parents.

They’re overjoyed, of course. But they’re also worried. They’ve seen the adverts warning parents-to-be about the risk of de novo mutations – genetic mistakes that occur inside sperm or egg cells, and affect the child. These mutations, the ads say, are much more common than previously believed and they can cause all kinds of problems: intellectual disabilities, autism, infertility, mental illness, heart malformations – pretty much anything.

The scariest part? Because these are 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. “The stakes couldn’t be higher. Why leave it to chance?”

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.”

This is likely to become possible in the next few years.

A paper just published in Nature reports on the Non-invasive prenatal measurement of the fetal genome. The technique relies on the fact that the blood of a pregnant woman contains DNA: hers, obviously, but also that of the unborn child. This cell-free DNA can be extracted and genotyped.

This has been possible for a few years, but until now, only fairly crude genetic information could be detected. An extra chromosome, such as in Down syndrome, is pretty easy to spot. This technique is already used to diagnose Down’s syndrome and a few other disorders prenatally.

But those diseases are just the low-hanging fruit at the tip of the iceberg, if you see what I mean. To gather the kind of detailed genomic information that could diagnose thousands of disorders is harder: the fetal and maternal genomes are mixed up, and the challenge is to tease them apart. But according to the Stanford geneticists behind the Nature paper, and other teams, it’s now possible as early as the first trimester.

What makes the new method so revolutionary is that it is, as the title of the paper says, non-invasive. It’s already possible to sequence a fetal genome, but it takes a surgical procedure involving inserting a needle into the womb, and a degree of risk. It’s not something you can just sit down and do – but blood samples are. So cell-free DNA will make fetal genomics a personal choice, a commercial product.

The resolution’s still not 100%, but inevitably, it will become cheaper, faster and more accurate as technology advances. This year we’re expected to see the cost of reading a whole human genome falling below $1000. Fetal genomes will be more expensive, but not enormously so. In 5 or 10 years, it’s likely to be affordable.


What will happen? I think there’ll be demand for such services. Most parents won’t do it, but enough people will that it will be a major issue. Just look at countries where boys are more valued than girls: a lot of sex-selective abortion happens. Today, it’s limited to gender, because it’s easier to determine a fetus’s sex than its genome. In 5 or 10 years, they’ll both be easy.

With demand will come companies to supply these services and, inevitably, advertizing. I doubt these adverts will be on TV, because there will be opposition to the whole idea and boycotts of broadcasters who run them. But we’ll be getting spam emails about it. People will worry even over the harmless mutations: a variant won’t need to be really associated with a disease, just believed to be, to make people panic.

Socially, it’s likely to be divisive. The anti-abortion types will obviously not approve. But it will drive a wedge between those who support abortion but oppose “discriminatory” abortion against the disabled, and those who support the right to terminations ‘for any reason, or none’.

Politically, there will be pressure to regulate this, but legally, it’ll be tricky. I can’t see how you’d prove that any given abortion is motivated by genetic concerns, so unless you ban abortion outright, that won’t work. Banning fetal (or all) genomics except under medical supervision might be possible, but people could always go (or send a few drops of blood) abroad to get around that.

I’m not sure where I’ll stand on this, but it looks very likely that we’ll each have to make a decision in the coming years.

ResearchBlogging.orgFan HC, Gu W, Wang J, Blumenfeld YJ, El-Sayed YY, and Quake SR (2012). Non-invasive prenatal measurement of the fetal genome. Nature PMID: 22763444

  • DS

    Economic stratification leading to biological stratification. Not good. Really really bad!

  • pqo

    non-invasive? Except from woman's body, you are arguing it will invade every sphere of society

  • Kamilla

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

    Man am I glad I don't have their nerve in my tooth! Really? The life of your baby matters? This baby who, with a bad diagnosis, matters so much they want to give the parents information that (as currently happens with approximately 90% of Trisomy 21 Diagnoses) will push them towards enging that baby's life before he takes his first breath of air?


  • Neuroskeptic

    Kamilla: Well, that was just my 'artists impression' of what these adverts are likely to say. They probably will be shameful.

  • petrossa

    Not me, i had a vasectomy at 23 years old. No way i'm going to burden myself with procreation. If humankind exists or not is totally immaterial.

    But one thing is for sure, this can only end very badly indeed. The interaction of genomes is unpredictable, decreasing variations ultimately will lead to an uniform genepool.

    Hubris never was more evident.

  • Alina

    Is it not possible to do the genotyping of the embryo during an in-vitro fertilization, before it is actually transplanted in the mother? Then you can be sure that you get a (genetically) healthy child from the start.

    By the way, I wonder what is the false alarm rate of the procedure you described. De novo mutation can occur at any stage of embryonic development, and in that case it would be present in some tissues but not in others. It might not affect the brain at all.

  • Ruben

    Not to mention crime.
    There's a simpler solution, if de novo mutations really mostly come from the male germline (as Keightley, 2012, concludes), then operation freeze-my-sperm would be a cheaper way to do this, with no substantial ethical qualms.
    And at the moment the probability of harmful new mutations at the age of 25 may just be the probability of a false positive during exome-comparison.

    “Freeze a gallon now, you owe it to your kids (and your species)”.

  • Anonymous

    It´s a fetus, not a person.
    The REAL problem is that these kinds of arguments will be used on the slippery slope of regulating abortion and limiting choice.

  • Neuroskeptic

    Anonymous: “The REAL problem is that these kinds of arguments will be used on the slippery slope of regulating abortion and limiting choice.”

    I agree that could well happen. That's not my intention, I'm just sketching out what I think will happen. As I wrote, “Socially, it's likely to be divisive…it will drive a wedge between those who support abortion but oppose “discriminatory” abortion against the disabled, and those who support the right to terminations 'for any reason, or none'.” That wedge could indeed be exploited by anti-abortionists.

  • Neuroskeptic

    Alina: IVF would be a much more powerful too, but also a lot more expensive and inconvenient.

    As for the accuracy: It depends how you define accuracy. Currently it's pretty low, see the papers for details, but it's only going to go up!

  • Anonymous

    Ever see the movie Gattaca? One of my top 10.

  • Anonymous

    I see no reason to oppose discriminatory abortion. If banned, the fetus would develop into a child in a family who does not want it. And there is no shortage of kids.

    Again, it is a fetus, not a person.

    If I accept the religious idea that there is something mystical about conception, then, well, to me, abortion should not be such a bad thing for the fetus. The lumps of cells go straight to heaven, as they have not sinned. They could perhaps be baptized post-mortem by our presidential candidate.

  • kromozome

    Ethical issues need to be sorted out. How soon before we can intervene with cell development and patch things out in DNA of the fetus.

    As an anonymous post pointed out: Gattaca! thats what I am reminded of too. Its an awesome movie with a message, only if we would understand it. We need to educate ourselves to differ information from knowledge.

  • Anonymous

    This is not new. OK, the technique in the paper is new, and exciting, for those disorders where diagnosis in utero can lead to a treatment for the child in utero or immediately post-birth (like the surgical treatment for spina bifida, or dietary adjustments for children with PKU). What's not new is the re-emergence (yet again) of eugenics. Garland Allen has some excellent articles on the topic of eugenics in America…particularly the fact that the eugenic movement in America not only predated that of the eugenics movement in Germany in the 1940s, but that it was strongly supported by the scientific establishment at the time. Just like it is now. And I'm speaking as a scientist. The pro-life (or anti-abortion, if you will) movement has been right about this one…our society has been moving back in this direction ever more rapidly, and allowing abortion on demand simply makes it easy to do a eugenics pogrom. Given our new government-oriented health care system, I would not be surprised to see the government getting involved in mandating these tests, and possibly mandating certain outcomes depending on the results of the tests. They are already involved in a variety of health-care related decisions, and that will continue to become more intrusive.

  • omg

    Abortion or abondoning the baby is the cheaper option and a realistic legislation to pass than Gattaca. The monster of eugenics is not a matter of personal choice of whether to have a baby or not because science says so but govts controlling populations with worldwide pandemics. Because they can. Biiowar spells the end of all wars apparently, not nulear because bombs can be counteracted. The current monopoly is pharmaceutics. That generic pill from India where lots of developing countries get their stash from could thoroughly be abused.

  • omg

    Liberal democracies advocate freedom at the expense of choice. The trajectory being control. Blablabla I'm so sick of politics.

  • Ruben

    Don't get so worked up, dear anti- and pro-abortionists!

    If the risk (from de novo mutations, not large-scale errors like trisomy 21) for the individual is high enough for people to worry, the cheapest solution would win and that's freezing your sperm when it's still good.

    This would NOT be like Gattaca, because children would not get the best genes, just not the ones that are nonsynonymous mutations of their parents' genomes.

    In SOME cases, with a known genetic mutation linked to disease in one parent, they might select the fetus without it (already happens as far as I know), but for most stuff that Neuroskeptic mentions (intelligence, autism, other mental illnesses) you wouldn't be able to improve on the parents' genomes.

    This borders on scaremongering and Neuroskeptic should take a stand.

    The biggest problem is that you'll have to be more careful to check whether that frozen yoghurt is what it appears to be.

  • Neuroskeptic

    Ruben: Sperm banking would help. But it relies on people being forward sighted enough to bank their sperm at age 20 (say) for their own future benefit maybe 10+ years down the line, what about the guys who just never get around to it? There will be many. And the rate of de novo mutations is non-zero, even at that age.

    We don't yet know how important de novo mutations are in disease. But even if they're in fact of minor importance, some people will probably believe otherwise – I mean, there are health scares about everything else, vaccines, foods, chemtrails, whatever; the only reason there aren't irrational gene-panics is that not enough people know their genome yet, I suspect.

  • omg

    Freeze your sperm for what? So you can have a baby at 60? I suspect there isn't a gene panic because people believe in falling in love and leaving offspring miracles to the Almighty. I'd be concerned about rationalized gene panics among scientists like those doctors who think they have every disorder.

  • Anonymous

    Given our new government-oriented health care system, I would not be surprised to see the government getting involved in mandating these tests, and possibly mandating certain outcomes depending on the results of the tests. They are already involved in a variety of health-care related decisions, and that will continue to become more intrusive.

    No, given that state governments have gotten more and more right wing, the real threat is, just like the outcry over the non-existent threat of sex-selective abortions, this will be just another excuse for them to limit the scope of government to women's bodies. You use the anti-choice scare words, “abortion on demand” guess what, plenty of people, including me, think that's a damn good thing. The choice to have an abortion belongs to the woman making that choice and her alone. Whether her reasons are good or bad to others is frankly none of their business. Abortion “on demand” by the woman is not eugenics, it is a woman making a choice as to what is best for her and her family.

  • Clathrin

    Eggs and sperm quality likely do take some hits with age, especially when mixed in with lots of alcohol or perhaps caffeine etc. However from what we know of biological systems, it would seem to me sperm fitness would wax and wane with the successes and failures of the individual. When Mike Tyson KO'd the unbeaten Leon Spinks in 90 seconds back in 1988, his sperm were undoubtedly swaddled with transformative testosterone surges while Spinks' perhaps pickled in cortisol and related stress hormones. Later on when Tyson walks into the nightclub the ladies in the know likely be swooning.

  • Clathrin

    From my point of view this well presented scenario may fall short of any reasonable decision to abort.
    The epilepsy and autism likelihood seems low just from a time and effort investment point of view for women at the 3 month point of gestation, even if there are no other siblings waiting for their new playmate. If you tell us what deletion in particular you might have in mind I can tell you better what I would do I that case after a brief look at the literature on it. These two conditions are quite contentious and frequently in part a bit bogus as is the assignment of risk therein. There do however exist several prognoses which if faced with as pregnant woman or consulting husband, I would not question abortion.

  • omg

    Anon, I choose life and birth control over pro-choice and silent genocide. You should watch how a fetus is aborted before rattling on like it's a matter of theoretical debate. There's a potential market for aborted fetuses. If women all over the world were informed like you then they'd be engaging in safe sexual practices. If they can't even do that like hell they should be given the choice of abortion. If the conception was a mistake, atone by raising a kid. Sex should remain sacred just like concieving life. It's been so cheapened by capitalism it makes e sick.

  • Anonymous

    I've had an abortion. I don't regret it. I don't consider myself evil or a murderer and yes, I used birth control and it failed and I am thankful that I live in a state where my bodily autonomy is respected and I am not a vessel for potential male life. So, yes, I've seen how a foetus is aborted, I've also seen and felt what it was like to have an unwanted pregnancy.

    You want to make sex and conception sacred, go ahead, you have the right to make that choice for yourself, not for anyone else. Using pregnancy as a punishment for women not making the choices you think they should make cheapens life much more than abortion.

    You want women to “atone” for having sex by having a kid? That's sickening.

    • Bones and Behaviours

      Oh look, we seem to have a shill among us.

  • BiolArtist

    Unfortunately, given the current trends to advertise any product that ties in with preliminary studies on health risks, it is all too likely that we will face this sort of personal eugenics advertising.

    The high rate of termination for Down's Syndrome babies is a perfect precedent. Given the current memes about autism being a tragedy, and the lack of empathy for autistics, I think this test would probably be very popular.

    Given the potential for high support costs, there may even be pressure on parents to do anything they can to prevent autism and/or epilepsy. I could see the local developmental disability agencies asking for proof parents had screened for disabilities and there was no sign the disability might occur. (Of course this would be even stronger if there was any hint of a family history.)

    Just as supplement manufacturers tout antioxidants as magical health-giving substances based on early (but not current) results, I suspect such tests would be marketed long before there's any guarantee of accuracy. Yes, having mutation X might be linked to a 10% incidence of autism rather than 1%, but there's no way to tell what level of severity in that 10%. The adverts will all emphasize the most disagreeable outcomes–nonverbal, non-toileting, self-injurious, institutionalized etc. stereotypes instead of acknowledging that there's a roughly equal likelihood of being an absent-minded professor, engineer, programmer, or artist.

    All they need to do is link to the Autism Speaks website for “awareness” of how dreadful autism is and why you need to make sure your future child won't have any.

  • Slippers647

    I think the advent of greater testing is wonderful.

    I for one spent most of my adult life caring for a disabled sister. Disabilities take a toll on families as those with disabilities have many needs that can conflict with other family members and partnerships. It takes very special caring people to embrace that kind of responsibility which will not only the parents but the other children in the family.

    I would never knowingly have placed those same burdens on my children who were already impacted by their aunt's needs.

    Then there is the huge medical, educational and social costs for programs for these people.

    I understand that minor anomalies such as hair coloring, heighth, skin color or osiety factors seem trivial to us but may be selective options 200 years from now.

  • omg

    Anon, you're full of s*. With an ultrasound you watched your baby's limbs get broken and sucked out with a vacuum. Having worked in an abortion clinic and lasting a couple months. Every mother who walked into that clinic was reduced to tears and regretted it. Obviously you don't know any better or you are indeed just evil. But I don't buy your stoic BS. Get help.

  • omg

    By the way, the pill is used in conjunction with your ovulation cycle. Don't have sex when you're fertile. If you can't follow instructions then carry around condoms. Better yet, get a vasectomy given you have such remorseless regard for life.

  • omg

    I meant Bilateral Tubal Ligation, I've assisted those too. Less risky than an abortion and no tears and regrets. I suggest you get some counselling for that abortion though. Those that advocate prochoice on the political front are not women who've actually had abortions.

  • retrun

    Yet with all this advance, the medical/insurance complex still treats pregnancy as a disease, birth as a medical procedure.

  • Anonymous

    omg: If you've worked at an abortion clinic then I'm the Queen of England. You have no idea how an abortion really works apart from the anti-woman propaganda you've been watching. Also, studies have shown that the vast majority of women feel relief after an abortion. I'm not stoic or evil, I'm human and I happen to be female, which I know makes me inferior and sub-human in your view. I don't need counselling because I made the right choice for me and my body, but I suggest you might want some for your misogyny.

    The vast majority of women and men have sex. You really think that telling people to stop having sex works? I mean abstinence-only education is so effective right? Not to mention that not every woman who has sex does so consensually.

    rerun: What would you characterise pregnancy as? It is a medical event, it poses medical risks. It isn't a disease no more than menopause is, but it still requires medical monitoring and intervention.

  • Anonymous

    @Anon I think you're being trolled. If not, better to act like you are and ignore omgs idiocy.

  • Anonymous

    @anon: Yeah I figured, it's just that those ideas are pretty much cannon in the anti-choice community and worth being challenged. Might not get through to a troll/idiot but worth a try.

  • Raul Trejo

    I think this is a good method to finding out if you have a healthy baby with good chromosomes so the parents can have time to decide in the early stage weather to abort or keep the baby without causing any major harm in a later stage such as abandoning the baby or killing it. I say this because there parents out there that want a healthy baby but do not want a baby with down syndrome and by detecting the bad genes early in the fetal stage will prevent parents from giving birth to a baby with down syndrome and having to abandon it because they wanted a healthy baby.

  • Mike S

    Thank for an interesting article. If civilization finds a way to survive itself we will see just the most amazing science done in the next few decades. Genetics already shows the promise of curing diseases or enhancing abilities. Who knows what else we may accomplish when we decode 'junk' dna further? Science will always move forward, we can only hope that culture does as well.

  • Bones and Behaviours

    Just separate choice from reproductive decisions, by relegating them to some kind of committee, and it will be much easier.

    ‘Reproductive choice’ here is the obstacle, moreso than the usual bioethics of abortion itself. Just as other case where laissez faire falls flat.

    Interestingly anti-individualist China is now moving against genetic screening for the common good – for the people over the individual.

    Time to get some state on those ovaries before its too late. Reproduction is demography and demography is a commons.

  • Bones and Behaviours

    Think of the case of XXY babies, 50% of whom are aborted (at least in Denmark) although most of them do not even show the full Kleinfelters Syndrome stereotype and usually live healthy if infertile lives.

    Note that XXY is a gender variant, so we may be seeing here today what happens when the gay gene is found tomorrow.

    Although I don’t see anything wrong with the desire to wipe out harmful genes, targeting an entire group of people like this is nonetheless correctly described as somewhere between ‘extermination’ and ‘genocide’ – it really is not something that should be taken lightly but some people seem quite flippant about bioethics.

    Most people, including those with such hereditary problems that we wouldn’t wish them to procreate, are at the very least capable of contributing something to the financial and human capital of a society. In all such cases termination should be reckoned as an antisocial act.

  • Emil Kirkegaard

    While this is the very near future, it is perhaps better just to wait and use embryo selection.



No brain. No gain.

About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.


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