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paleoanthropology, genetics and evolution

genetics and society

  • Genetics without the disclaimers

    Thu, 2011-03-17 15:48 -- John Hawks

    The NY Times covers a new genome-wide association study of SNP variants and response to exercise ("Is Fitness All in the Genes?").

    The phenotype is improvement in maximum oxygen consumption volume. Some people have rapid improvement with exercise and others don't. Straightforward enough, and there is one SNP that accounted for 6 percent of the phenotypic variation, which is quite strong as far as these associations go. Usually GWAS associations explain a much smaller fraction of the phenotypic variance.

    The final few paragraphs of the article irritated me. It's like these stories have to follow a form, with a long disclaimer at the end. They report the facts -- variant explains 6 percent of variation -- and then they proceed to preach about how the facts may not matter:

    “It will be years, if ever,” said Dr. Bouchard, before gene tests exist that can reliably separate high and low responders. Even if and when such tests become available, he continued, the results will not constitute an excuse for skipping workouts. “There are countless other benefits provided by exercise,” he said, apart from whether it raises your VO2 max. “Exercise can reduce blood pressure and improve lipid profiles,” he said. It can better your health, even if, by certain measures, it does not render you more aerobically fit.

    More fundamentally, Dr. Bouchard said, elements of the interplay of genetics, environment, the human body and resolve probably always will remain mysterious and stubbornly individualized, no matter how much science disentangles the genome. People who don’t have an ideal version of the ACLS1 gene to prompt aerobic improvements from exercise, for instance, might harbor a different, unidentified gene that just makes exercise feel enjoyable, regardless. So, too, might someone whose body is genetically predisposed not to respond aerobically to running blossom during weight training sessions.

    Hello? Six percent of the variance is six percent of the variance. The article ought to just say that 94 percent of the variance is not explained by this SNP. That answers the question! That unadorned fact tells you that the SNP isn't strongly predictive about exercise response for any single person. To do even better, the article ought to tell us how much of the total variance is explained by all the SNPs together.

    I know, statistics can be difficult for NY Times readers, but honestly explaining the result would take a lot less space than what the article does do, which is to give us a long litany of "mysterious and stubbornly individualized." And the "different, unidentified gene that just makes exercise feel enjoyable, regardless."

    Come on, people! Why not just tell us about earth spirits and auras?

    The moralizing always goes the same direction. You'll never hear hand-wringing about how we can't trust exercise because it only predicts a small proportion of the overall variance in mortality risk. What about the "mysterious and stubbornly individualized" people who are healthy at 80 without ever lifting a barbell?

  • Genetic bike path

    Wed, 2010-09-29 08:30 -- John Hawks

    Eva Amsen describes her trip down the BRCA2 cycle path, near the Sanger Institute in the UK. She also points to Jennifer Rohn's description of the path last year.

    The path was opened in 2007, and includes the 10,000th mile of cycle path in the UK. The nearby Sanger institute (famous for its genome sequencing) suggested to decorate the path with a gene, and BRCA2 was chosen because it also has approximately 10,000 base pairs, but also because it's a gene that people can relate to. Genetic screens for breast cancer risk are something that people will have heard of, and this is the gene that those tests look at.

    Amsen has pictures of the path which give a good impression of the scale. What an interesting way to personalize the information in a genome; I wonder if the positions of mutational variants are marked?

  • Heritability and genetic test essay

    Fri, 2010-09-10 11:40 -- John Hawks

    Neuroscientist Dorothy Bishop provides a student-level opinion piece in the Guardian that addresses the "missing heritability" problem without using the term: "Where does the myth of a gene for things like intelligence come from?".

    It's an unfortunate headline, because she doesn't disagree with a strong genetic influence on personality, intelligence or other behavioral traits. Bishop merely explains that they are polygenic, with few genes of strong effect. The "myth" is the assumption that there's "a gene for" a trait, instead of many genes influencing a trait.

    Consider one of the more reliable associations between genes and behaviour: a gene known as KIAA0319 which has been found to relate to reading ability in several different samples. In one study, an overall association was reported with a p value of 0.0001, indicating that the likelihood of the association being a fluke is 1 in 10,000. However, this reflected the fact that one gene variant was found in 39% of normal readers and only 25% of dyslexics, with a different variant being seen in 30% of controls and 35% of dyslexics.

    Some commentators have argued that such small effects are uninteresting. I disagree: findings like this can pave the way for studies into the neurobiological effects of the gene on brain development, and for studies of gene-gene and gene-environment interactions. But it does mean that talk of a "gene for dyslexia", or genetic screening for personality or ability, is seriously misguided.

    This is far from saying there's "no gene" for dyslexia; but the public could use much more discussion of what these genetic studies actually show, and much less sensationalizing of the "scientists find gene for dyslexia" variety.

    I know, I'm preaching to the choir here. What I don't understand is why we keep having to make this point, after thirty years of headline writers getting this wrong time and time again. I won't blame science writers for this one, because the real problem is the sound byte.

    I don't fully agree with the piece, in that I think Bishop underestimates the prospect of genetic tests. Sure, testing a single SNP does no good for most traits, but in the long run we will see many quantitative traits for which multi-locus combinations predict phenotypes a lot better than chance.

    Still, the general point holds. Right now, family history is a better predictor of most traits than any genetic assay. Having a twin gives you the best prediction of all -- which is another way of saying that the heritability estimates from twins and other pedigrees that Bishop discusses are the evidence we need to account for genetically.

  • Eating their young

    Thu, 2010-09-02 11:12 -- John Hawks

    Ally Fogg: "Why the young get a bad press" reports on research into age and media bias:

    Silvia Knobloch-Westerwick of Ohio State University gave 276 volunteers an online magazine to browse. She found that older people preferred to read negative news about young people, rather than positive news. What's more, those older readers who choose to read negative stories about young individuals receive a small boost to their self-esteem as a result. Younger readers, in contrast, prefer not to read about older people at all.

  • Genetic lapidaries

    Thu, 2010-02-18 11:06 -- John Hawks

    Nature News has a short piece on yesterday's Desmond Tutu and other South African genomes: "Africa yields two full human genomes."

    Has anybody else noticed how it has become routine to print a short list of phenotypic associations whenever a new genome is published? Last week, the press about the Greenland genome emphasized mostly uninformative data about earwax type and hair form. It was all stuff you would have predicted anyway. Now, what pearls of information have come from the African genomes?

    Several of the DNA changes in the Khoisan may reflect adaptations to the rigorous life of a hunter-gatherer in the Kalahari Desert. Three of the Khoisan carry a version of the muscle-expressed ACTN3 gene linked to faster sprinting. !Gubi carries one copy of a form of the CLCNKB gene that encodes a cell-membrane channel capable of reabsorbing chloride ions in the kidney, a possible advantage in the desert. And all have a form of the taste-receptor gene TAS2R38 that would enable them to taste the bitter compound phenylthiocarbamide. This form of the gene may help hunter-gatherers to avoid toxic plants.

    The Khoisan also lack a gene variant giving protection against malaria infection by Plasmodium vivax. This could reflect their lifestyle, Schuster says: with both water and cattle scarce, the Khoisan face little threat from malaria. But as agricultural communities encroach on the Khoisan habitat, or more Khoisan take up farming, the population may find itself increasingly vulnerable to infection.

    OMG! They're PTC tasters! I'm so happy they sequenced the genome for that; those test strips really put a dent in the budget at $2.50 per hundred!

    The information is accurate, but these genotypes just aren't very interesting. We already knew that Duffy O is rare in southern Africa. That's another cheap phenotyping test. Are they under threat from vivax malaria? A little -- but that certainly won't help them when falciparum is the main threat. ACTN3 may not have been known already, but isn't surprising at all.

    I think there are two problems here. One: putting out this list of variants really misrepresents the purpose of the sequencing. Genotyping known variants is not the point of these sequences. If it were, the geneticists could have accomplished that with a $400 chip. Finding unknown variants is more worthwhile (and the number of new polymorphisms has been listed in some articles), but we don't know what phenotypic correlations a newly-discovered polymorphism may have. So, we get this catalog of known variations -- written like a little lapidary of genetic gems -- which is just window-dressing for the real science.

    Two: The point of having whole genomes or genome-wide genotypes is that they give us the opportunity to test hypotheses about systems of genes instead of individual genotypes. But for the most part, we don't know how to do that. Certainly on my end, looking for the causes of recent human evolution, we just haven't made great methodological progress on how to study the simultaneous evolution of many genes and their joint effect on human biology. Here in my lab, and elsewhere, we're trying really hard -- and that is to me the exciting part of this science. But we're far from the point where we can predict much from a genome.

    One aspect that hasn't gotten the attention it deserves: These genomes have a tremendous amount to tell us about the Pleistocene history of African populations. This is like an ancient record of thousands of genes, representing this area of the world where only a handful of ancient human fossils exist. Much more on that later.

  • Mailbag: Race, words and definitions

    Mon, 2009-08-24 09:56 -- John Hawks

    I believe this problem with the word "race" which biologists have needs to
    be handled as a communication problem. The way that biologists use the term
    is, like the word "species" Darwinian, but that is not what "normal" people
    mean. The flexible concept of an interbreeding population is fine and clear
    to me, but it is not what most people think of when they read about
    biologists proving the existence of races and species.

    I think this is what prompted most anthropologists to jettison the word. But then there are two strains in anthropology that are hard to reconcile with each other. One strain rejects the word "race" with its unpleasant social correlates, but pretty much retains the nineteenth-century concept. Another strain rejects the concept of race entirely.

    This of course becomes confusing because we can see statements like "anthropologists all agree there's no such thing as race," but in fact some really do believe there are no such groups, while others believe in such groups for all intents and purposes but refer to them only with Orwellian terms!

    I don't have any answer, really, but you're certainly correct that it's a public communication nightmare. In my classes, I estimate half the students just assume that anthropologists are lying about race.

  • The trouble with contamination

    Mon, 2009-03-30 22:50 -- John Hawks

    A case in Germany illustrates how easy it can be for contamination to sneak into labs from unexpected sources:

    Police in Germany have admitted that a woman they have been hunting for more than 15 years never in fact existed.

    ...

    She was alternatively called the "woman without a face" and the "phantom of Heilbronn" after the city in southern Germany where she allegedly killed a policewoman.

    Police suspicions were based on traces of identical female DNA they found at 40 crime scenes across southern Germany and Austria.

    ...

    Now it has been determined that the cotton swabs used to collect DNA had been contaminated accidently by a woman working at an unidentified factory in Bavaria.

    The company selling the swabs did not claim they were DNA-free or certified for use in DNA analysis.

  • Bobsleds, no; sprinting, yes

    Thu, 2008-08-21 10:53 -- John Hawks

    If you're interested in athletic performance and genetics, read Daniel Macarthur on ACTN3, sprinting, and Jamaica:

    At this point I probably should confess to having a more than casual interest in this story: I was one of the authors on the first study showing an association between this gene and elite athlete status back in 2003, and this gene has been the central focus of my research for a good part of the last six years.

    ...

    It is almost certainly true that Usain Bolt carries at least one of the "sprint" variants of the ACTN3 gene, but then so do I (along with around five billion other humans worldwide). Indeed, I'm fortunate enough to be lugging around two "sprint" copies - but that doesn't mean you'll see me in the 100 metre final in London in 2012.

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Neandertals

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Malapa

Just outside Johannesburg, the Malapa site is producing some of the most exciting finds in human evolution. This site is the headquarters of the Malapa Soft Tissue Project.