Donegal skeletons may offer clue on cystic fibrosis

 

WHAT COULD A collection of medieval human skeletons found in south Donegal tell us about cystic fibrosis in Ireland? A new study plans to find out – by analysing DNA from the skeletons’ teeth for mutations in the cystic fibrosis (CF) gene, writes CLAIRE O'CONNELL

Archaeologists unearthed the 1,250 skeletons during excavations in late 2003 along along the route of the N15 Bundoran-Ballyshannon bypass at Ballyhanna.

The site is thought to have been used for burials around the 12th century AD, and for several years researchers at IT Sligo and Queen’s University Belfast have been analysing the remains for evidence of diet and health, in a project funded by the National Roads Authority.

A new aspect of the study will now seek to find out how frequently the medieval humans carried a particular DNA mutation that contributes to cystic fibrosis.

“We are trying to find out was there a difference in the mutation 800 or 900 years ago,” says Dr Jeremy Bird, head of science at IT Sligo.

We all carry two copies of the gene associated with CF, but the condition arises when a person carries mutations in both copies that stop the gene from working normally. The incidence of such “homozygous” CF in Ireland is one of the highest in the world, at one in 1,353 at birth. And within the Irish population, one person in around 19 carries a mutation in one copy of the gene.

“We are looking for the carriers of one particular mutation, F508, which is the predominant one [currently] in the Irish and most Caucasian populations in Europe,” says Bird. “And because the carriers are one in 19, if we look at 100 individuals from Ballyhanna and then predict on a modern basis you would expect to find five individuals carrying it.”

But what’s not known is whether the ratio of carriers was the same back then, and the fortuitous discovery of the Ballyhanna bones offers an opportunity to find out, he notes.

“We have got an ancient collection of material that allows the numbers to be done, there’s little point in looking at one skeleton.

“We have access to a large amount of material – here we have 1,250 individuals who may represent a medieval Gaelic population that would have seen relatively little movement at the time.

“Dublin would have been more confused; you’d have Viking migration, so there are more questions there. But in the north-west of Ireland it is seen as a population that has not been interfered with by plantation or Nordic populations.”

The researchers are collaborating on the project with Prof Philip Farrell at the University of Wisconsin, whose group is looking at the history of CF mutations across Europe.

But just taking some DNA samples from the skeletons and identifying the genetic mutation is not as straightforward an exercise as it sounds, because the ancient DNA could be contaminated with more recent genetic material, according to Bird.

“Modern DNA is ubiquitous in the environment – run your finger along a shelf and you’ll pick up dust that’s principally epithelial cells from humans, so modern DNA is everywhere,” he says. “You can recover DNA, but have you got ancient DNA?”

However, initial studies on teeth found at the Ballyhanna site indicate that the medieval DNA is suitable for the study, and under licence from the National Museum of Ireland the project will now analyse DNA samples from molars in 60 individuals for the delta F508 mutation.

“If the indicator ratio is exactly the same, then that’s good to know,” says Bird. “But if there’s a major change – if it’s not one in 19, if it’s one in 50 or one in 10, you have to think what are the candidates for this.

“The populations were becoming urbanised, there were major changes and there were new diseases coming on the scene, such as TB, which had a huge impact on urban populations. So there were all kinds of selective pressures happening. It opens up debate.”