Cystic fibrosis in Ireland

Chris Smith put this question from Dee to geneticist Patrick Short...

Patrick - Yeah absolutely. It's a very good question and this is also the case for example in places like Finland as well as many Greek islands or other places, anywhere where you've had, at least in the past, some kind of either relative isolation or else a big population bottleneck. If you had a small number of people that go and colonise a place to begin with then the amount of genetic variation that went into that colonizing event means that certain disorders that may have been relatively rare to begin with just happen to end up being common. So the example I'm most familiar with is Finland, but I think it probably applies in Ireland as well, but only about 2000 people colonised the country some tens of thousands of years ago. Then if one or two of those people had a particular disorder then as that population expands it can be at quite a high prevalence and also the existence of any kind of clan structures or mating structures that mean people are more likely to mate with one another. Can cause these to increase further still.

Carolin - So is that also the case for Iceland, because I have read that that's quite a closed gene pool isn’t it? And it's of great interest to researchers for that reason. Do they also have this issue about these diseases?

Patrick - Yes and the genetics research that goes on in Iceland is quite amazing. They're very soon going to have genome sequenced the entire population. They also have genealogical records going back for many generations but I believe it is the case there as well that there's a number of disorders that are at particularly high prevalence that there are specific research priorities for that country.

Chris - Is it worth considering also that these genes that we regard as disadvantageous under certain circumstances the reason they might be in those populations and have risen to such a high prevalence could be because in the past one other function of those genes is to confer some kind of advantage under certain circumstances and therefore they become concentrated in the population and while they're disadvantageous if you have the right environment they're advantageous under other conditions.

Patrick - Yes that's absolutely right. One of the best examples of this is is the gene that causes sickle cell anemia that also confers a resistance to malaria. So you can, if you have two copies of the gene, of the mutation, then you're likely to have sickle cell but if you have one it's actually protective from malaria. So you end up with this balance. But in places in the world where malaria is not an issue then it's often at much lower prevalence and there's lots of other great examples.

克里斯,我想专门th之一e diseases that Dee mentions in her question is cystic fibrosis and we've learned in recent years that the gene that is linked to cystic fibrosis happens to also confer resistance to certain salmonella infections. And so we think that's one of the reasons why that gene is so common in the population because people would have had some degree of resistance against typhoid for example historically. So it became more concentrated in the population.

Patrick - Yes. The other interesting thing about cystic fibrosis is there’s a single mutation that is, that accounts for a large fraction of the cases. There's all sorts of mutations that can cause it. But whenever there is a single mutation that's very common, it's often, can depend on the frequency within a particular population how frequent that disease is in general so probably that delta 508 mutation that's quite prevalent cystic fibrosis happens to be very common in Ireland for reasons that we may or may not have figured out yet.