New Mutations – New Eugenics?

By Neuroskeptic | August 25, 2011 9:00 pm

True or false: you inherit your genes from your parents.


Mostly true, but not quite. In theory, you do indeed get half of your DNA from your mother and half from your father; but in practice, there’s sometimes a third parent as well, random chance. Genes don’t always get transmitted as they should: mutations occur.

As a result, it’s not true that “genetic” always implies “inherited”. A disease, for example, could be entirely genetic, and almost never inherited. Down’s syndrome is the textbook example, but it’s something of a special case and until recently, it was widely assumed that most disease risk genes were inherited.

Yet recent evidence suggests that many cases of neurological and psychiatric disorders are caused by uninherited, de novo mutation events. Here are two papers from the last few weeks about schizophrenia(1,2) – but the story looks similar for autism, intellectual disabilities, some forms of epilepsy, ADHD, and others. Indeed they’re often the same mutations.

Biologically, a given mutation is what it is, whether it’s de novo or inherited. But on a social and a psychological level, I think there are crucial differences, and in particular I think that if it turns out that de novo mutations are important in disease, we’re going to see attempts to take these variants out of circulation – far more so than in the case of the very same genes, were they inherited.

The old eugenics movement was based on the idea that if we stop people with bad genes from breeding – by sterilization, voluntary or otherwise, say – we’ll be able to eliminate diseases and other undesirable traits. This idea is now generally regarded as extremely unethical, but many of its opponents have shared with the eugenicists the belief that it could work.

But if de novo mutations are what cause the majority of disease, then this approach would be pointless. Sterilizing certain people, or encouraging the healthy ones to have more children, would never be able to eliminate the ‘bad genes’ because new ones are being created every generation, pretty much at random.

So the de novo paradigm ought to be welcomed by opponents of eugenics. It wasn’t just morally wrong – it was biologically misguided too.

But hang on. This is the 21st century. We have in vitro fertilization (IVF), and you can analyze the genes of an IVF embryo before you decide to make it into a child. In the near future, we might be able to routinely sequence the genome of any unborn child shortly after conception.

From there, it would be a small step to allowing parents to decide not to have children with de novo mutations.

This would be, in its effects, a form of eugenics – in the sense that it would produce the effect that the old eugenicists wanted. No more ‘bad’ variants, or not nearly as many. Opinions will differ as to whether it’s morally different. But I would have said that politically, it’s a lot more likely to happen.

I can’t see forced sterilization returning any time soon. But if you were expecting a baby and you knew that it was not just carrying your and your partner’s DNA, but had also suffered a mutation – might you not want to avoid that?

Psychologically, it matters that it did not inherit the variants. It would be a big step to decide that your child should not inherit part of your own DNA. Of course, some variants are obviously harmful, like one that raises the risk of cancer, and I can’t see how anyone would want to pass those on. But think about the grey areas – a variant for social anxiety, mild autistic symptoms, obesity, a personality trait.

You might well feel that carrying that variant is what makes you, you; and so it would be natural for your child to have it. You might decide that if it was good enough for you (and all your ancestors), it’s good enough for your children. You might well resent the very idea that it’s a ‘bad gene’ at all, as an attack on your own self-worth.

But none of that applies if it’s a de novo mutation. Indeed, quite the opposite – all those same considerations would probably lead you to want your children to carry as close as possible to a carbon copy of your DNA, with no random changes. It was good enough for you.

My point is that I think there will be much more support for the idea of genetic screening or other action against de novo variants than against inherited ones. More people will want it, it will be more socially acceptable, and used more widely. I’m not saying this would be a good or a bad thing, just making a prediction. In the future, diseases and traits that are primarily caused by de novo mutations will increasingly selected against.

  • http://www.blogger.com/profile/07125980057827981457 Manoel

    Uou mention a gente for personality trait. Could you point me any paper that argues that there is such a thing as a gene for personality trait (spcially genes for the big Five)?

    Thanks
    Manoel

  • http://www.blogger.com/profile/09374512270335764119 Maia Szalavitz

    Have you tried IVF? If not, I can assure you that you needn't worry much about this form of eugenics: the natural way of having sex is way better than shooting up for two weeks or more, potentially nasty hormonal side effects, typically at best a 30% chance of success per try, not to mention around $15,000 a pop.

    Universal health care would never cover “cosmetic” IVF and few people are insane enough to prefer it to sex.

    Maybe it will get better in future, but until then, this is a theoretical worry.

  • http://www.blogger.com/profile/08820607553556177222 SustainableFamilies

    The picture gets more convoluted if you look at some of the research on resiliency and some of the polymorphisms considered assotiated with bipolar/schizophrenia/autism— Also something interesting the kids who had some of those polymorphisms were the MOST affected by bad environments. They were also MORE affected by good environments meaning the high risk polymorphism kids with the GOOD environments did the best of anyone. So is there more to this picture? Just saying. I'm not saying it's quite this simple– I am saying that genes are influenced by environment to mutate in specific ways and that some of the mutations may confer benefits we aren't taking into account:
    “The authors tested the evolutionary genetic hypothesis that the functional form of an asymmetrically risky Gene × Environment interaction will differ as a function of age-related antagonistic pleiotropy (i.e., show opposite effects in young vs. old individuals). Previous studies have identified a polymorphism in the human IL6 promoter (rs1800795; IL6 -174 G/C) that interacts with adverse socioenvironmental conditions to promote chronic inflammation in older adults (elevated C-reactive protein). This study identifies a protective effect of the same polymorphism in 17- to 19-year-old adolescents confronting socioeconomic adversity. Over 60% of the environmental risk contribution to the IL6 × Socioeconomic Status interaction could be accounted for by interpersonal stress and adult role burden. Thus, the IL6 -174G allele does not represent an undifferentiated risk factor but instead sensitizes inflammatory biology to socioenvironmental conditions, conferring either genetic vulnerability or resilience depending on the developmental “somatic environment” that interacts with social conditions to influence gene expression. (PsycINFO Database Record (c) 2011 APA, all rights reserved).”

    http://www.ncbi.nlm.nih.gov/pubmed/21639625

    http://www.ncbi.nlm.nih.gov/pubmed/21637770
    “The 7-repeat allele appears to protect against the adverse effect of CA since the decline in resilience associated with increased adversity was evident only in individuals without the 7-repeat allele. “

    “Moreover, long allele (?5-repeat) and 7-repeat allele of DRD4 exon III VNTR were found to be associated with significantly increased opioid dependence risk (OR, 1.50; 95% CI, 1.24-1.80 and OR, 1.57; 95%, 1.18-2.09, respectively”
    http://www.ncbi.nlm.nih.gov/pubmed/21714067

    “Results indicate that higher levels of risk at birth were associated with less sensitive parenting only among mothers carrying the 7-repeat allele, but not among mothers carrying shorter alleles. Moreover, mothers who are carriers of the 7-repeat allele and whose children scored low on the risk index were observed to have the highest levels of sensitivity.”

    http://www.ncbi.nlm.nih.gov/pubmed/21603618

    And this is pretty profoundly demonstrative that a risk gene could offer benefits in positive environments:
    “Participants with the DRD4-7 repeat (7R) allele who experienced parental problems had the highest scores for unresolved loss or trauma whereas participants with DRD4-7R who did not experience parental problems showed the lowest ratings.”
    http://www.ncbi.nlm.nih.gov/pubmed/21506030

  • http://www.blogger.com/profile/08820607553556177222 SustainableFamilies

    I was talking 7-repeat allele of DRD4 exon III VNTR which I havent read much abobut being as related to schizophrenia or bipolar as much as the 5HTR2A polymorphisms and the like…. but it wouldn't surprise me if these polymorphisms had benefits we haven't noticed yet either— like what if the T102C variations associated with poor outcomes were actually protecting against influenza or something? Meaning yes they cause bad stuff, but they are providing something positive to a compromised cellular environment…

  • http://www.blogger.com/profile/08820607553556177222 SustainableFamilies

    I guess I'll put it more simply, de novo mutations arise in specific cellular environments in the womb– toxins, influenze, high levels of inflammatory cytokines, altered hormonal profile etc in the mother— may actually be causing the mutations to purposefully arise in direct response to meet a cellular need that is abnormal compared to the “normal” conditions in the womb— as defined by what has been normal accross generations. If the cells are being stimulated that the environment is drastically different than it has been for a number of generations— meaning the cells are needing to function differently than has been needed for previous generations, the cells will make alterations to attempt to match the demand for different cellular funtioning to meet a different environment. Mutation.

  • http://www.blogger.com/profile/12525104555859213125 Socrates

    An Autistic writes: Goodbye Cruel World.

    Die Erbkranke will now go self-medicate with Jack Daniels in a doomed attempt to re-inflate his punctured sense of self-worth.

  • pseudonymoniae

    @neuroskeptic

    I could definitely envision a world wherein we might accept certain gene variants as part of “normal” human variability, while rejecting the majority of de novo mutations (presumably all of those which are deleterious) as “abnormal”. It's definitely a perspective worth considering.

    Somehow I don't think that a relative abundance of de novo mutations in the human population would sway the beliefs of many eugenicists. Yes, from a rational perspective this makes sense: why would we need to selectively breed the human population when natural selection already takes care of the most harmful mutations and new mutations might be popping up at any time? But given all of the arguments against eugenics, I kind of wonder whether those few remaining proponents might be beyond using their rational faculties on this topic.

    @sustainable

    Your last comment is a fair bit off base in at least one respect. There is no known biological mechanism by which a targeted mutation might be elicited to meet some environmental need. On the other hand, there is a much simpler mechanism which could accomplish what you're talking about. One of the big hypotheses out there in epigenetics is that certain early-life environments might lead to long-term changes in gene expression that are protective for that particular environment.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Manoel – Well, that one was a hypothetical example :) There are papers reporting on genetic associations with Big 5 personality (e.g.) but I'm not convinced by them. And they tend to be inherited mutations, not de novo. However if de novo mutations are important in autism and schizophrenia, I would be surprised if they weren't also associated with some aspects of personality.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    pseudonymoniae – I don't know any modern-day eugenicists so I can't say how they'd react to this, but if I were one, I'd be worried.

    Other people who should be worried are evolutionary psychologists who have attempted to explain the persistence of schizophrenia and autism etc. genes in the population by pointing to a fitness benefit of carrying those genes – the idea that in the Stone Age, people who had schizophrenia genes became shamans or whatever.

    If it turns out that most of the mutations causing schizophrenia, say, are de novo, all those stories would collapse.

  • veri

    De novo and new eugenics?

    '…Engdahl carefully documents how the intellectual foundations of 'eugenics,' mass culling of the sick, coloured, and otherwise disposable races, were actually first established, and even legally approved, in the United States. Eugenics research was financially supported by the Rockefeller and other elite families and first tested on Jews under Nazi Germany. …'

    You make eugenics/”eugenicists” sound normal? It's not.

    I don't see how 'de novo' has any bearing to eugenics when the mutations could be arbitrary whatevers that could be genetically sequenced or not later on.

    Linking this to mass culling is pushing it – NS, I didn't take you for a drama queen.. maybe the opponents (normal people) of panspermia could say de novo explains why aliens (future generation) have diseases.

  • omg

    '…the idea that in the Stone Age, people who had schizophrenia genes became shamans or whatever.'

    Oh LORD – someone's been smoking.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Hey, not me, that's a published theory. Here's just one schizophrenia-shaman paper:
    http://ww1.cpa-apc.org:8080/publications/archives/cjp/2003/february/polimeni.pdf

    “Polimeni and Reiss have proposed a group selection hypothesis
    for schizophrenia with a different emphasis: schizophrenia
    could have enhanced a shaman’s ability to conduct religiousbased
    rituals (59). Because religious rituals are universally
    observed in all cultures, this activity is likely both genetically
    rooted and critical to humankind’s survival. With the exception
    of the last few thousand years, humans have always lived
    in hunting and gathering societies that all demonstrate some
    form of shamanism. Therefore, a genetic foundation to shamanism
    must also be considered. Psychosis would be advantageous
    to shamans spearheading religious rituals.”

  • http://www.blogger.com/profile/12987483359214068938 Will:Power

    with regards to genetics and illness/mood disorders, environmentally induced epigenetic modifications are another a major gene influencing variable. epigenetic changes do not change the gene but rather switch it on or off, these states may then be passed on and inherited. increasing numbers of genes are being found to be regulated epigenetic factors, such as the glucocorticoid receptor, BDNF and BACE1/PS1 which lead to enhanced amyloid-b generation.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698240/
    http://www.ncbi.nlm.nih.gov/pubmed/20644477
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930664/

    eugenics: i think gene therapy for mood disorders will never be straight forward. for instance many of the genes associated with intelligence and creativity seem likely to be related to increased mood disorder risk when combined with others, and relevent genes may only turn bad in the wrong environment, the role of which is typically underestimated in most chronic illnesses.

  • http://www.blogger.com/profile/06645477927492218010 Pedro

    My gosh. We are seeing the Neuroskeptic turning into Adolf Hitler

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Oh no. I specifically said that I'm not saying that I think this would be a good thing.

    I'm just making a prediction as to what I think will happen. I'm not saying anything about what ought to happen.

    Anyway, Hitler would have been devastated to learn that most diseases were caused by de novo mutations because it would have undermined his whole genetic-hygine policy. If 'good' genes could turn 'bad' at the drop of a hat, the whole notion of good and bad bloodlines would be fairly silly.

  • Ivana Fulli

    Haven't we got now a plausible enough explanation of why schizophrenia doesn't become extinct just because the sufferers have fewer children.

    On the same evolution front some aspies say that they are the future of man because many autistic traits help nerds drive Mercedes on the Silicon Valley and the mercedes might help them to bred and reproduce more often plus neurotipical skills like good handwriting are useless in a world full of computers.

  • http://www.blogger.com/profile/04924150491150942391 JohnB

    This comment has been removed by the author.

  • http://www.blogger.com/profile/04924150491150942391 JohnB

    Em, regarding eugenics –

    http://tinyurl.com/3hr2cdp

  • http://bounds.net.au Stephen

    BTW, any evidence that de novo mutations could be positive as well as negative?

    Also, are there any figures on what % of new births have a de novo mutation?

    This, at least, would be a comparatively easy test: just randomly sample 10,000 parents and their children and see how many match 100% from either parent.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Stephen: De novo mutations can be beneficial. That's how evolution happens – a good mutation happens, helps the organism to survive & reproduce, and is hence passed down to offspring.

    What's interesting (as Ivana Fulli points out) is the question of whether mutations that might once have been 'bad' are now becoming 'good' due to changes in the environment.

    There are also lots of mutations which just don't do anything at all.

  • http://www.blogger.com/profile/08820607553556177222 SustainableFamilies

    “There is no known biological mechanism by which a targeted mutation might be elicited to meet some environmental need.”

    …YET.

    ;)

  • http://www.blogger.com/profile/08820607553556177222 SustainableFamilies

    In reading about plant evolution, germline mutations, and rates of mutations, it appears that it seems frequently mentioned that epigentic mechanisms influence rates and types of mutations and that those epigenetic alterations are affected by the environment.
    Just somethin to think about:

    “Decades of work have elucidated the existence of two forms of heritable information, namely genetic and epigenetic, which are collectively referred to as the 'dual inheritance'. The underlying mechanisms behind these two modes of inheritance have so far remained distinct. Cytosine deaminases, such as activation-induced cytidine deaminase (AID) and other members of the APOBEC family, have been implicated both in genetic variation of somatic cells and in epigenetic remodeling of germ and pluripotent cells. We hereby synthesize these seemingly dissociated functions into one coherent model, and further suggest that cytosine deaminases, particularly AID, might have a broader influence by modulating epigenetic information in somatic or cancer cells, as well as by triggering genetic variation in germ and pluripotent cells through mutation followed by natural selection. We therefore propose that the AID/APOBEC family of deaminases are likely to have acted as drivers throughout vertebrate evolution.”

  • http://www.blogger.com/profile/08820607553556177222 SustainableFamilies
  • http://www.blogger.com/profile/10140892511467377191 ivana Fulli

    Maia Szalavitz

    Have you try to raise several severely autistic children?

    Besides you just need to make love withe the man(men) of your choosing, have screening and abortion.In china and India the sex ratio mother nature intended is modified by abortion not by IVF.

    I think Neuroskeptic fears are a real issue.

    I just disagree on his manly expectation of mother dreaming of producing an offspring just like their husband: we women want the best for our children.

  • http://www.blogger.com/profile/12033918835169823548 MJ

    Stupid question, do de novo mutations occur at the same rate with IVF as they do in the general population?

    I understand that these mutations are random but in many cases, the word “random” is just another way of saying that we don't understand how it happens. It seems possible that the different conception and very early prenatal environments could have an effect on the mutations that are seen and how often they occur.

  • http://www.blogger.com/profile/08820607553556177222 SustainableFamilies

    “It seems possible that the different conception and very early prenatal environments could have an effect on the mutations that are seen and how often they occur.”

    This is absolutely the case.
    ” Finally, the effects of paternal age: there is a significantly increased risk of the disease with increasing paternal age, which could result from the age related increase in paternal de novo mutations. This is the case for autism and schizophrenia(3). The male-to-female ratio of mutation rate is estimated at about 4-6:1, presumably due to a higher number of germ-cell divisions with age in males.”
    http://www.ncbi.nlm.nih.gov/pubmed/21712793

    “A survey of the research literature identified 9 environmental factors for which increased pre-conceptual exposure appears to be associated with increased risk for autism. Five of these factors–mercury, cadmium, nickel, trichloroethylene, and vinyl chloride–are established mutagens. Another four–including residence in regions that are urbanized, located at higher latitudes, or experience high levels of precipitation–are associated with decreased sun exposure and increased risk for vitamin D deficiency. Vitamin D plays important roles in repairing DNA damage and protecting against oxidative stress–a key cause of DNA damage. Factors associated with vitamin D deficiency will thus contribute to higher mutation rates and impaired repair of DNA.”
    http://www.ncbi.nlm.nih.gov/pubmed/19699591

    Also influenza virus and maternal smoking tend to affect gene function:
    “In frontal cortex of mice born to influenza virus-infected mothers, the 5-HT(2A) receptor is upregulated and the mGlu(2) receptor is downregulated, an alteration that may be involved in the behavioral changes observed.”

    It is my suspicion that there is very little “spontaneous” about “spontaneous” germline mutations. In general there have to be certain factors present or absent in the cellular environment to cause them to fail to make needed repairs that are usually meticulously regulated.

  • Pseudonymoniae

    @sustainable

    That paper describes an enzyme which can increase the rate at which mutations accumulate in cells. It says nothing about any mechanism by which environmental factors, or any other factors, might target this enzyme to affect specific genes.

  • http://www.blogger.com/profile/10140892511467377191 ivana Fulli

    Thanks Pseudonimonia

    I had no time either to mention that British theory about vaccination causing autism.

    I was saving my skin not talking science at all and was very bad as a politician since I forgot also to pay tribute to the testosterone theory of Pr Simon Baron-Cohen, a potent man in the field of autism whom help I must ask if I ask political aylum in GB.

  • http://www.blogger.com/profile/06487907863785174174 Dov Henis

    Rethink :

    Genome Evolves By Culture, Natural Selection, Not Randomly
    Tags: genetic mutations, RNAs are organisms,

    A.
    Rate of de novo mutations and the importance of father’s age to disease risk
    http://www.nature.com/nature/journal/v488/n7412/full/nature11396.html

    B.
    RNA nucleotide genes are ORGANISMS, life’s primal ORGANISMS.
    Genomes are template ORGANISMS evolved by the RNAs for carrying out their – RNAs’ – natural-selection tasks.
    All life’s activities originate and evolve for the survival of the RNAs.
    THIS is Darwinian evolution.

    C.
    Modified RNAs expressions are NOT random mutations. Some of them are caused accidents, but not random. Apply Darwinism to them.
    There is no randomness in the universe that evolves from all inert mass, singularity, to all moving mass, energy, and probably back again.
    Now, after a century of strangled Enlightenment, it’s time to restructure science plans, policies and budgets.
    The viable future of humanity is not with natural selection, but with scientism, the follow up of Enlightenment.

    Dov Henis (comments from 22nd century)
    http://universe-life.com/

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Neuroskeptic

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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