The 1000 Genomes Project

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."

Chinese

[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].

1 in 2000 people

[rsidd]

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:Selection

[Arthur Grumbine]

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.

Re:1 in 2000 people

[Cassius Corodes]

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 particular outcome - which increases further the number of people they need to detect disorders.

Not 1 in 2000

[RML]

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.

Rare Conditons

[MassiveForces]

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.

Re:Question

[David Munch]

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, infection-induced DNA mutations or due to spontaneous DNA mutations, are usually killed of by specifik immune defence killer-cells, that can recognize cells that are different from the others. But in the end, some persist and becomes uncontrollable, like cancer-cells that divide extremly fast. Many mutations are silent though, meaning that even though the end product, the proteins, are different from 'normal', they can act as if nothing had happened.

Re:Chinese

[Ajehals]

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 (educated at home and abroad), unless of course you are suggesting that there is some ulterior motive that we should be ascribing to China.

I think it is great to see funding coming from multiple nations, working together, especially given how this kind of research should benefit all of us in the long run, it shows that countries that can afford it are still putting money into research (something that you wouldn't believe if you read some of the science related news in the media). Although I must say I am beginning to get concerned with the level of hostility and suspicion being levelled at certain members of the international community, it is reminiscent of the the suspicions between east and west during the cold war, I had hoped that now that is over we could start to see real global co-operation ans opposed to confrontation and competition (although competition may well be beneificial).

misleading science

[cinnamon colbert]

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 there are two copies (except the x and y sex chromosomes) one from dad and one from mom
Since these two copies are different, it matters, a lot, what differences are where.

Chromosomes are diploid!

[bcwright]

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 specific genes. The easiest to understand are those genetic diseases that are dominant - that is, you need only one copy of the gene in order to have the disease. On average, a dominant genetic disease which has a frequency in the population of 1 in 1000 would have about a 50% probability of being represented in the sample.

The situation is more complex for genetic diseases caused by recessive genes - which form the majority of genetic diseases. People carrying only one copy of the disease will be asymptomatic but a 'carrier' of the disease so that their children would have some chance of getting the disease if their other parent was also a carrier of the disease. However even there, you often have a good idea who might be a carrier for the disease based on family history: how many others in that person's family are affected. If any of those individuals are the person's children, you know that that person is a carrier for the disease; if one of them is a (full) sibling, then there's (at least) a 50% chance that the individual is a carrier, etc.

These sorts of familial relationships are the bread-and-butter of traditional investigations into genetic diseases, and this promises the ability to multiply their effectiveness. In effect you are getting a window into the genomes of many more individuals than merely those whose genomes were sequenced.

Biology geek solves your problem for you.

[NIckGorton]

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, the disease exists when an individual is qq. So qq = 1/2000 = 0.0005. So q (the prevalence of the allele) is 0.02. So you would expect that 1/50 people has the q gene (almost all of them as heterozygotes who have one p and one q gene.) If a gene exists in 1/50 people and you sample 1000, the odds that you wouldn't find it is pretty remote.

There fixed it for you. No need to thank me.