None So Blind

There have been several articles in the literature claiming that the gene frequency of the 35delG allele of connexin-26, the most common allele causing deafness in Europeans, has doubled in the past 200 years, as a result of relaxed selection and assortative mating over that period.

That’s fucking ridiculous. I see people referencing this in journal articles and books. It’s mentioned in OMIM. But it’s pure nonsense.

Advertisements
This entry was posted in Uncategorized. Bookmark the permalink.

24 Responses to None So Blind

  1. TWS says:

    So what is the frequency is it increasing or decreasing? Why the bs about the increase?

  2. pauljaminet says:

    What’s ridiculous? Presumably not the doubling in gene frequency — this gene has a lot of variants, http://www.ncbi.nlm.nih.gov/pubmed/23073770, so there’s something going on there, and genes have pleiotropic effects so you can’t infer from one trait that a variant has negative fitness. Presumably it’s the explanation, relaxed selection and assortative mating, which is pure speculation.

  3. gcochran9 says:

    The doubling of gene frequency in 200 years is ridiculous. Impossible.

    In Europeans, one variant, 35del G, accounts for about 70% of all connexin-26 mutations. This variant is surprisingly common – the gene frequency is about 1.5% in Southern Europe.

    Surprising because having two copies makes you profoundly deaf. In the good old days, deaf was a fate worse than death – you were left without language. It also must have reduced your fitness to near-zero. Which makes the high frequency mysterious.

    In the 90s, researchers seem to have assumed that this was a mutational hotspot, with the same mutation occurring again and again. For at least 12 years (well before the crazy articles I mentioned) it has been clear that this was not the case – all the copies of 35delG have the same haplotype. It happened once.

    The only way you’re going to see such a high frequency of an effectively lethal recessive in a continental population is if it conferred a reproductive advantage in heterozygotes. The required advantage must have been as large as its gene frequency, something around 1-2%.

    So it’s like sickle-cell.

    Now, if you decreased the bad reproductive consequences of deafness, what would you expect to happen? Gradual increase, at around 1 or 2% a generation, if the carrier advantage held – but it probably didn’t. It was probably a defense against some infectious disease, and those have become much less important. If there was no longer any carrier advantage, the frequency wouldn’t change at all.

    In order to double in 200 years, you would need a carrier advantage > 9%.

    Assortative mating,deaf people marrying other deaf people, would not make much difference. Even if deaf people substantially out-reproduced normals, which they don’t, only ~1-2% of the copies of 35delG reside in deaf people.

    if 35delG had been a mutational hotspot, it would have had the highest mutation rate of all genes (by far!) – about 1 in 4000 per generation. Under relaxed selection, say no fitness penalty at all for being deaf, that frequency would begin to increase. If the gene frequency was 1.50% 200 years ago (about 8 generations) , it would have increased all the way to 1.70% by today. It would take more like 1500 years to double the frequency.

    35delG has had some social important in deaf culture, because it’s the only common deaf-causing mutation. Deafness is caused by mutations of many different genes, and usually when deaf people marry other deaf people, their kids can hear. But a significant minority have connexin-26 deafness. When members of this subgroup marry each other, their kids are deaf (deaf of deaf) – highly desirable if you’re a nut.

    • pauljaminet says:

      Those are great points. … The paper I cited said the prevalence was 7% in Iran. So immigration from Muslim countries to Europe could be a source of increasing allele frequency. To double from 0.7% to 1.5% prevalence in southern Europe you’d only need 10% of the population to be Muslim immigrants, which I think is about what has happened. … Although a doubling due to selection effects in Europe in the last 200 years is impossible, allele frequency must have doubled many times in the past to reach a 7% frequency in Iran. So there must have been positive selection for the heterozygous state.

      • gcochran9 says:

        Read more carefully. They were looking at the relative frequency among deaf people, not the general population.

      • pauljaminet says:

        Yes! Sorry, busy today; though my point that admixture can significantly change allele frequencies in a short time is still valid…. Something odd about these numbers: If a single allele appears in 1.5% of the population but a single allele is present in only 7% of the deaf, then it seems like there must be many homozygotes who are not deaf. … I see on this page that the prevalence of hearing loss is thought to have doubled in the last 30 years (http://www.asha.org/public/hearing/disorders/prevalence_adults.htm) — perhaps there are gene-environment interactions and recent environmental changes are making these alleles more likely to express as hearing loss, maybe they didn’t cause deafness as easily in the past.

  4. Abelard Lindsey says:

    Autism has increased 20 times over a 20 year period (1991-2011). What would account for such a dramatic increase in such a short time. One would think this rules out a genetic explanation for the increase in Autism.

  5. James Thompson says:

    As regards autism, I think there is general agreement that it is being diagnosed too liberally. “Autistic” is currently more acceptable than “learning difficulties”.

  6. ghazi-less says:

    So, it seems we are heading toward a pathogen hypothesis?

  7. Jim says:

    Freud was one of history’s greatest charlatans.

  8. j.plenk says:

    Breeding math geniuses by herding them in silicon valley( some think tanks seem to beisland populations) seems to dramaticaly increase the incidence of autism7aspergers syndrome-

    • gcochran9 says:

      I guess asking for evidence would be low-class.

      • j.plenk says:

        Cambridge Psychologist Baron-Cohen published quite a bit in this direction, and as i work trauma surgeon in military medicine in Europe and we are also assessing abilities in recruits it matches my experience, that many mathematicaly highly talented young men are single minded have little social contacts and often lack leader talent/social skills. With many traits it can be postulated that more of a good thing is not necessarily going to improve the outcome:very evident in medicine. That there is only one INTELLIGENCE AND THAT IS REPRESENTED BY THE ABILITY TO DO CALCULUS IS CERTAINLY A SIMPLIFICATION WITHOUT EVIDENCE TO BACK IT! That diffferent fields of talent/excellence may need the expression of different gene-combinations which lead to the construction of different brains is hence postulated by neurogeneticist Dan Geschwind from the UCLA. Charles Darwin himself learned a lot by watching modern breeding techniques lead to rapid changes in livestock breeds ( and allready warned of the dire consequences of inbreeding that has ruined so many former working breeds)- and breeding hunting hounds myself i can confirm: you can´t have everything at once, excellence in one field often impaires performance in an other!
        Regards, Johannes Plenk

      • j.plenk says:

        Of course highly educated people tend to have children later in life, if at all( ther is a lot of discussion in europe how intelligent people, especially women are removing themselves from reproduction) so high parental age could be the reason for rising prevalence of mild autism/asperger´s syndrome among their children.

  9. Maybe they are wearing 35delG signs, or have a secret handshake or something. It would make assortive mating and selection easier.

    Or pheremones. Everyone knows that deafness sharpens your other senses, so they must be tracking each other downwind.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s