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The 1000 Genomes Project

Posted by kdawson on Wed Jan 23, 2008 02:18 AM
from the reaching-for-statistical-significance dept.
Biotech Science
jd writes "An international consortium of specialists in genetics has announced the 1000 Genomes Project, in which at least 1,000 people from around the world will have their genomes fully sequenced as part of an effort to discover the relationship between genetics and disease. At present, over 100 regions of DNA are known to be related to illnesses, but the maps that exist are vague and are drawn from an extremely small population pool. According to the article, this results in the need for slow, expensive, and laborious studies to pinpoint causes, especially for rarer conditions. This project aims to find conditions that might only appear once in every 2,000 people (though how they intend to do that with half that number is unclear). The researchers hope to massively speed up the diagnosis of genetically linked illnesses and to improve the reliability of such diagnoses."
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Submission: 1000 Genomes Project by jd (1658)
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  • Chinese (Score:2, Informative)

    by Anonymous Coward
    I wonder why there's so much funding coming from China for this project.
    You can see the list of all participants (including funders) here [1000genomes.org].

    • Re: (Score:3, Informative)

      by Ajehals (947354)
      The three countries with groups funding this are The US, China, and the UK, (although there is no indication of the proportion of funding being supplied by which), in each case the funding is being provided by organisations that exist to further science, in some cases specifically genome research. If you look at the other elements of the study you will see that pattern repeated, so I guess it is a case of (in the words of Jim Hacker) "great nations working together to answer the great questions of our age.
      • Why you singled out China is surprising, especially given the rate of growth their economy is showing and the sheer number of graduates in the sciences that China produces each year

        Agreed, folks in the US seem to think they hold a monopoly on scientific acumen, when in fact, our hold isn't "slipping", it's passed into "slipped". Other nations have been rocketing past us in terms of not only scientific growth, but social and financial as well. The people in the US are told on a daily basis that they liv

        • Listen, John Edwards, I know the campaign isn't working out too well for you, but you're not going to save it by posting on Slashdot.

      • I had hoped that now that is over we could start to see real global co-operation ans opposed to confrontation and competition


        You must be new here.

  • Selection (Score:5, Insightful)

    by mastershake_phd (1050150) on Wednesday January 23 2008, @02:24AM (#22150358) Homepage
    This project aims to find conditions that might only appear once in every 2,000 people (though how they intend to do that with half that number is unclear).
     
    Well, they could sequence the DNA of people known to have rare diseases.

    • Re: (Score:1, Troll)

      by jd (1658)
      That rules out discovering what causes some people to become lawyers.
    • Unfortunately, I think their sensitivity to peoples' privacy will prevent them from doing just what you suggested.

      From TFA:

      These people will be anonymous and will not have any medical information collected on them, because the project is developing a basic resource to provide information on genetic variation. The catalog that is developed will be used by researchers in many future studies of people with particular diseases.
      • I don't know why everyone is so sensitive about Scientists and Medical Professional have access to your medical information, the real problem is usually the high school educated billing clerk in the basement of the hospital or your insurance company. If a hospital told the average six-pack Joe that they'd rebate half his co-pay if he let them send in his medical info and DNA for research and longitudinal study he'd jump at it.

    • RTFA (Score:4, Insightful)

      by RML (135014) on Wednesday January 23 2008, @03:51AM (#22150752)
      There are other projects that sequence the DNA of people known to have rare diseases such as cystic fibrosis, and there are projects that sequence the DNA of people with common diseases like heart disease, but we don't know much about the variants in the middle that are neither very common nor very rare. This is an attempt to fill in that gap in our knowledge.

    • Rare Conditons (Score:4, Informative)

      by MassiveForces (991813) on Wednesday January 23 2008, @03:58AM (#22150776)
      Finding diseases that eventuate in 1 in 2000 people with a genomic study of 1000 people is entirely possible... with one thousand people you have two thousand sets of genes. Since most genetic diseases are caused by two of the same recessive alleles (usually resulting from broken genes) in a single haplotype there would be lots of carriers; those with a single disease allele that could be spotted as a major deletion relative to the genomic reference sequence.

    • IANA Scientist, but the article seems to portray it as if they are simply trying to make a catalog of what normal variations exist.

      But, there is one part that still does confuse me. From TFA:

      These people will be anonymous and will not have any medical information collected on them, because the project is developing a basic resource to provide information on genetic variation.

      Wouldn't it make much more sense to have a detailed listing of their medical history? For example, if one of those people has Alz

    • Using 1,000 samples, won't you get about half of the conditions that occur once in every 2,000 people? For that matter, won't you get 0.1% of those that occur once in a million? There are a lot of conditions out there.

  • 1 in 2000 people (Score:5, Informative)

    by rsidd (6328) on Wednesday January 23 2008, @02:29AM (#22150392)

    This project aims to find conditions that might only appear once in every 2,000 people (though how they intend to do that with half that number is unclear)

    Let's try to make it clearer, then.

    The probability that a given condition appears in an individual is 1 in 2000, or 0.0005. The probability that it does not appear in that individual is 0.9995. The probability that it does not appear in any of 1000 individuals is 0.9995^1000 = 0.6 approximately; and the probability that at least one of the 1000 individuals has it is 0.4. Not bad at all. (If you used 2000 people, the probability that at least one of them would have it would improve to about 0.6.)

    Suppose you aren't interested in just one conditions, but in lots of conditions -- say, ten of them. The probability that at least one individual would have at least one of those conditions is 1 - 0.9995^(1000*10) = 0.993 == ie, practically certain.

    They really ought to teach basic probability theory in schools...

    • Re:1 in 2000 people (Score:5, Insightful)

      by nacturation (646836) <nacturation@gmail. c o m> on Wednesday January 23 2008, @02:57AM (#22150562) Journal

      This project aims to find conditions that might only appear once in every 2,000 people (though how they intend to do that with half that number is unclear)

      Let's try to make it clearer, then.

      The probability that a given condition appears in an individual is 1 in 2000, or 0.0005. The probability that it does not appear in that individual is 0.9995. The probability that it does not appear in any of 1000 individuals is 0.9995^1000 = 0.6 approximately; and the probability that at least one of the 1000 individuals has it is 0.4. Not bad at all. (If you used 2000 people, the probability that at least one of them would have it would improve to about 0.6.)

      Suppose you aren't interested in just one conditions, but in lots of conditions -- say, ten of them. The probability that at least one individual would have at least one of those conditions is 1 - 0.9995^(1000*10) = 0.993 == ie, practically certain.

      They really ought to teach basic probability theory in schools...

      Your post is like that scene in Indiana Jones with the guy making some really impressive sword moves, looking all menacing... while Indy just pulls out his revolver and shoots him. You could get a whole room full of geeks cranking numbers and arguing over how many people they would need to find in order to exceed a particular probability that any one participant has Lou Gehrig's disease, while a simpler person would leave the room, come back the next day, and say "Hey guys, meet my neighbor Bob... he has Lou Gehrig's."
       

    • Re: (Score:3, Insightful)

      by Ignis Flatus (689403)
      they really ought to teach basic genetics in schools.

      you neglect the fact that each person has two sets of genes, one inherited from their mother, the other from their father. that brings the total number of genes to 2000 sets. and it's also likely they're interested in many more than ten conditions. so you should think more in terms of a probability density function of conditions found versus their rarity.

      • I thought this too (two sets of genes) - but its useless if they find a gene for a rare disease in a person if its not expressed (and hence not detected by the researchers). Hence having two sets of genes does nothing but complicate things further (as they now have to find which particular gene out of the two is the one causing the problem).

        Furthermore another issue is that the genome is one huge causality network - for all but the most simplest disorders you'll need to have a cascade of genes to get a p
        • well, that's what computers are for, sifting haystacks. and surely they're interested in far more than just rare diseases. most all of us end up taking a handful of pills by the time we're 65. cardiovascular disease, cancers, and dementia are where the money's at.
          • Google could get in on this.

            Knowing them they would attack the problem at right angles to how its normally tackled.
            Just like how they made their translation service by feeding stacks of data in to a probability engine to get a extremely accurate translator, they could throw in tons of genetic data and out will pop the answers with pretty good accuracy.

            These sorts of problems are ideal for brute force techniques like that.
            Only problem is you need one of Google's datacenters to do it properly.

            • Re: (Score:3, Interesting)

              by jd (1658)
              I'm not convinced it's coincidental that Google's research space was announced shortly before this project. I suspect Google is/was thinking along very similar lines. BLAST may be adequate for many things, but GoogleBLAST would be about what it would take to crunch any significant collection of entire human genomes.
        • one huge causality network ... you'll need to have a cascade of genes to get a particular outcome

          And if you, on top, follow the idea that physical conditions (starting at the molecular level, INGBER [childrenshospital.org]) are a major determinant of gene expression you might eventually come to your own conclusions regarding the value of simply linking 'the genome' to conditions of ill health.

          CC.
        • You do realize that genomic data is extremely noisy; they take the DNA and break it into pieces that start with a known sequence of base pairs and end with a known base. Then the problem is to reassemble the broken pieces into the most likely way that is not the only way. It's like putting together a jigsaw puzzle that has pieces missing, extra pieces present, wrong pieces that go together and no picture on any of the pieces.

          The first pilot will involve sequencing the genomes of two nuclear families (both p

      • they really ought to teach basic genetics in schools.

        Um, they did back when I went to high school. What they really need to do is do a better job of teaching stat math so terms like 1/X won't confuse those that made it through high school educated people when the sample size is smaller than X.

        In college, you learn most stats, polls, and surveys are just plan lies to push you in the desired direction.
    • It's sort of right. Usually the phenotype will be recessive - so two bad copies need exist for the condition to be seen but only one bad copy needs to exist for it to be a useful sequence. For example, although the frequency of cystic fibrosis in Caucasians is 1/400, but the allele frequency is 1/20. So you need to look at the square root which gives you much higher probability of a hit. (BTW, the frequency in Asians is I believe on the order of 1/500,000 so CF could be cured simply by outbreeding - and no
    • Also, don't forget that each person has two haplotypes, one from each parent, so
      when one sequences a person, one captures the variation on two human genomes at once.

      Of course, this all relies on the coverage you sequence at, and one option for
      the 1,000 genomes project is doing this at low (2x?) coverage, using pretty sophisticated
      methods to combine statistical power between sample datasets.

      The "1,000" though is more a round number that is in the right range. it might well be
      1346 people or something like th
    • Yes, but only some fraction of those will have both the genetic propensity and the symptoms of the condition. Some other fraction will have just the genetic propensity. Yet another fraction will have identical symptoms from an unrelated cause. If the overlap that has both is unknown, you have problems. If family history data indicates that it is likely to be one in ten, then the 0.993 drops to 0.0993. Of the fraction that have a genetic propensity, there may be N different possible genetic causes that have
    • If we assume the populations are at Hardy Weinberg equilibrium (which they will not be for all diseases as there is some negative selection on afflicted individuals) then we use the formula p^2 + 2pq + q^2 = 1. If q^2 = 1 in 2000 then p is 0.9776 and q is 0.0223. This means that the rate of carriers of the disease is 0.9776 * 0.0223 * 2 which is 0.043. If we multiply it out to see what are the chances of taking 1000 people and none of them being a carrier it is (1-0.043)^1000 which gives us the extremely

    • They really ought to teach basic probability theory in schools...

      Or maybe basic biology maybe? The Hardy-Weinberg equation plus a little basic algebra solves the problem:

      p + q = 1

      p^2 + 2pq + q^2 = 1

      P and q are the frequency of a specific gene (assuming there are only two variants, but lets KISS.) Each organism has two copies of a given gene. They can be pp, pq, or qq. So the number of p genes and q genes must equal 100%. And the number of people who are pp, qp, or qq must equal 100%, hence the two equations.

      In the case of a simple autosomal recessive gene, t

      • Many replies in one, here; and a day late so I guess nobody will read it.

        If a gene exists in 1/50 people and you sample 1000, the odds that you wouldn't find it is pretty remote.

        But you'd only care if you see the disease. That's the point you and other geneticists above are missing. Otherwise you'd never know whether the gene is linked with a disease in its variant form, or is harmless.

        For the story to be convincing, in your sample population, you need to show that one person has the disease AND tha

  • 1000 Gnomes Project? (Score:4, Funny)

    by Aereus (1042228) on Wednesday January 23 2008, @02:34AM (#22150426)
    I have no idea what they plan to do with 1000 gnomes, but I can only guess that whatever it is will end in a giant explosion.

    • Re:1000 Gnomes Project? (Score:4, Funny)

      by Hognoxious (631665) on Wednesday January 23 2008, @03:24AM (#22150644) Homepage Journal

      I have no idea what they plan to do with 1000 gnomes
      Replace them with KDE?
    • Found them [wikimedia.org]. Commenting on this article may be closed now.

    • I have no idea what they plan to do with 1000 gnomes...

      Hmmm... They could use the 1000 gnomes as a baseline data to determine:

      - how many gnomes are needed to be joined end - to - end to encircle the earth
      - at the equator
      - at the horse latitudes
      - how many are needed to drill from the america and out to china
      - the number of gnomes needed to reach the moon and back
      - the volume of gnomes needed to fill a library of congress
      - the difference between a metric gnome and t

  • This is really awesome. For too long, the "human genome" has been what we know of a few guys who ran the HGP. Since then, many more have been sequenced but not systematically, and not for the sole purpose of cataloging the countless variations present. This sort of database is the first giant leap towards effectively creating a solid understanding of human variation, allowing us to perfect everything from medical treatment to diet supplements (the GATTACA option in the poll is so relevant). Really, this

  • This is fantastic news (Score:5, Insightful)

    by Biotech9 (704202) on Wednesday January 23 2008, @03:09AM (#22150600) Homepage
    Anyone reading up on the progress in genomics over the last decade has seen the huge leaps in speed and accuracy and the insane cuts in cost to work with nucleic acids.

    From a lab level where what used to be a weeks work with lots of chemicals and processing is now usually a 20 minute protocol with a kit from Quagen. what used to be massive amounts of work with hundreds of gels and digestions and labeling steps to analyse nucleic acid sequences is now a few days with an affymetrix kit, giving far more accurate and useable results. Across every step this progress has been rapid.

    And in the future, near-term like within a decade, all these methods will become outdated and replaced with near-realtime analysis and diagnosis. The best point in all of this is that no matter how advanced medical tech has become, the limiting factor has been that it's necessary to actually BRING your disease ridden body to the hospital or doctor. The rise of companies like www.decodeme.com [decodeme.com] is what i expect DNA assesment to be like in the future. You send off some samples you scrape off your cheek yourself, and within a few days you get a full diagnosis on any known predisposition to disease or genetic problems.

    Which is why a lot more attention should be put into the debate on morality and genetic profiling. It's going to be here before you can blink, it might be nice to know what you think about using embryo selection to wipe out CF before it becomes a possibility.
  • I've got marfan syndrome. I am really eager to have my genome sampled so that this condition is better understood.

    www.marfan.org

  • Not 1 in 2000 (Score:4, Informative)

    by RML (135014) on Wednesday January 23 2008, @03:35AM (#22150678)

    The scientific goals of the 1000 Genomes Project are to produce a catalog of variants that are present at 1 percent or greater frequency in the human population across most of the genome, and down to 0.5 percent or lower within genes.
    A frequency of 0.5% is 1 in 200, not 1 in 2000. That's much easier to find with a thousand genomes, especially since they're not trying to figure out what the variations do, just that they exist.

  • Astonishing (Score:2, Insightful)

    by Anonymous Coward
    What do we propose to do once we have genetic maps anyway? Scientists (especially within the drug industry) have no clue what they're doing - all we do is "best guess" diagnoses, and then pump people full of drugs that may or may not help, and that induce more serious side effects than they're supposed to be "helping".

    This whole idea of "early detection" pisses me off; it just reminds me of the drug industry. It really does come down to the almighty human thinking they know what they're doing. Hopefully we
    • I know people who those "New Drugs" have worked wonders on.

      And as we know more, genetic therapy will become more effective. But feel free to go to live in a tribe somewhere if you hate progress that much.
    • There is some degree of truth to that. For example, the exact effects of a new drug aren't always clear until there have been several years of study - even after approval. It would not be particularly hard to use tracer isotopes in early pre-approval testing, and then use well-established imaging techniques to determine exactly what component of a drug affected what and how. I would not be at all surprised if this was already being done in some cases. You'd then obviously also need to use the same imaging t
  • finish grade 11-12 science did they...
    (though how they intend to do that with half that number is unclear)
    Here's how... [wikipedia.org] Alleles.
  • When scientists use the word "complete" they are being misleading. There are very large, difficult to sequence regions (, heterochromatin,, eg centromeres) that have not been sequenced, ever, and that are biologically important (centromeres are required in every cell division, to ensure that each cell has the proper set of chromosomes.)
    Even within the "normal", euchromomatic, sequencable DNA, there are gaps that have not been sequenced.
    Beyond this, you need to know haplotypes - that is, for most of your DNA
  • I recently took part in a small genetic survey for the auto-immune disease Ankylosing Spondylitis [wikipedia.org] (AS), a disease my wife has had for nearly a decade. It doesn't have the publicity of Lupus, but there are far more people suffering from it.

    Before the survey, only one genetic marker was known for the disease: HLA-B27, uncovered over three decades ago. If you have that genetic marker, you're almost certain to get AS ...but only 40% of AS sufferers actually test positive for HLA-B27. One survey later, we now kn

  • Remember that human chromosomes are diploid - we have two copies of (most) genes. (A few of the genes on the male Y chromosome have no analogue on the X chromosome, but that's a very small percentage of the human genome). So in total they will have roughly 2000 samples for each gene - 2 for every individual.

    Of course, that doesn't provide a correlation with specific genetic diseases - but here classical genetics techniques allow you to get an insight on how some of those diseases might be related to spec

  • What would we get if we calculated out the averages for every sequence, created an artifical DNA strand with that sequence, and grew it using cloning technology? Some kind of perfect man, or a genetic freak?

    I think I'd make a good mad scientist...
    • Does an individuals DNA structure change at all through out ones life time?

      Not in the sense you probably mean: your DNA does not adapt or "change" during your lifetime. Some cells have some changes to their DNA, either by accident or on purpose, but that generally amounts to inactivating or removing genetic material that a specialized cell won't be needing anymore before its death.
    • Some individual cells' DNA may change (usually for the worse - that's how you get cancer), but those mutations are probably much less common than the errors generated by the DNA sequencing machines. Both sorts of errors are filtered out because each piece of the genome is sequenced several times for each individual, and a computer combines the results.

    • Re: (Score:2, Informative)

      by David Munch (939296)
      Does an individuals DNA structure change at all through out ones life time?

      I believe you are talking about the DNA sequence, and not the structure of DNA itself? The DNA sequence is relatively unchanged throughout your life. The only things that changes it, are spontaneous mutations and pathogen-induced mutations (Bacteria, but especially viruses). Most of the time, cells with lethal malfunctions in their DNA undergo self-killing, known as apoptosis. Others that behave unnormally, either due to infection,

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