We are all special (genomically)

By Razib Khan | May 16, 2012 11:32 pm

John Hawks already discussed the Keinan and Clark paper in Science, Recent Explosive Human Population Growth Has Resulted in an Excess of Rare Genetic Variants. To borrow a critique, much of human genomics up to this point has been WEIRD. A reanalysis of the same finite population sets, over and over. No longer. Soon thousands upon thousands of whole genomes will come online, and innumerable rare alleles will start filling the background in. The ultimate end point of this will be when whole families have 100X coverage, and a set of unique mutational variants to each individual within the family unit will become known.

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  • Tawast

    Razib,

    Can we get any help with those rare alleles in genetic genealogy?

  • April Brown

    Not sure if this question completely relates, but I was wondering if there is a difference in ‘usefulness’ for the genome (right word?) for people from rare exotic ethnic groups and people who know exactly where they hail from, as opposed to somebody like myself who comes from a muddled European immigrant mix with no documented family tree past grandparents. It seems that mapping out small identifiable groups makes the coolest charts.

    I’m planning to do the 23andme thing at some point, but since I can’t correlate any of the findings to any documentation of origin, I was under the impression that my drop of data in the bucket wouldn’t be of much use to the big picture. I hadn’t really considered rare allele patterns – makes sense that even if there’s nothing remarkable going on in my family tree, fleshing out data is still helpful.

    (The chances of getting the living members of my family to get their DNA… sequenced, again, right word?, is not that great, unfortunately. I can see how getting an entire family to do it would give interesting results).

  • Dm

    We’ve been resequencing specific loci, dozens kbs at a time, hundreds thousand times, and the curious minds have been asking the same question over and over again, “just when the newly discovered variation will *finally* peter out”. Well one of the most reasonable approximations of the rank-frequency plot has been a hyperbola with the power of negative 1. Which of course won’t ever converge, speaking in mathematical terms. In practical terms, in means that new mutations are being formed at a feverish rate even as we expand sequencing. In population dynamics terms, it hints at the exponential growths of the humankind with a relatively modest loss of new variation through drift. The most recent (and the most populous) generation contribute the most (and the rarest) de novo variation.

    Practically again, it means that any panel composed of known SNPs, no matter how large, will always miss a large subset of the actual variation.

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    Practically again, it means that any panel composed of known SNPs, no matter how large, will always miss a large subset of the actual variation.

    how about when you 100X every newborn? :0)

  • Dm

    #4 every newborn?

    heheh, speaking of things practical :) Well, to capture *all* the variation which makes each of us genetically distinct, it’s not like you could ever avoid sequencing. Too much de novo stuff happens.

    If your goal is more modest, for example, to make sure that you capture a set %age (say 95%) of the variation … my point is that in a population with a recent history of sustained exponential growth, you still can’t avoid sequencing. But perhaps a generation or two in the future … as the population replacement rate nosedives, and severe drift of rare variation takes place … then perhaps a large set of allele-specific tests will become almost as good as sequencing. Of course since sequencing is supposed to become dirt cheap much sooner, we probably won’t care by then.

  • Dm

    BTW what do you make of Nicholas Wade’s interpretation in NYTimes that rare recent disease variants may be associated with high morbidity, while more common and older disease alleles gotta be less penetrant to avoid being selected against? If the new alleles are strongly selected against and disappear soon after they appear, wouldn’t they have a very different frequency distribution?
    http://www.nytimes.com/2012/05/18/science/many-rare-mutations-may-underpin-diseases.html?ref=health

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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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