UK (Queen’s University Belfast) Genetic causes of bone tumours discovered in 1,000-year-old Irish skeletons

The scientists were analysing skeletons from a “lost” graveyard  at Ballyhanna, where the remains of some 1,300 children, women and men were found during construction of the N15 Bundoran-Ballyshannon bypass.

The land would have been owned by the church and the Gaelic medieval population would have included tenant farmers, labourers, merchants, artisans, clergy and the very poor.

The study, which has been published in the European Journal of Human Genetics, is the first time a new disease mutation has been discovered in ancient genomic data.

The research team analysed genome sequences from the two affected skeletons and identified mutations in a gene called EXT1, which is known to be involved in Multiple Osteochondromas in modern patients.

The mutations found were different in the two individuals; one has been identified in some patients today, but the other has not previously been seen in sequencing data.

The researchers believe that life would have been particularly challenging for the men as the condition is rare, can be extremely painful and can lead to limb deformity, reduced stature, nerve compression and, in ~ 5% of cases, malignancy.

It only occurs in 1 in 50,000 people and when it is found within a modern locality the affected people tend to be related. However, in this study the same rare condition occurred twice in the same parish but resulted from two different mutations – the lightning of genetic tragedy struck twice.

Iseult Jackson, from Trinity’s School of Genetics and Microbiology, is the first author of the paper. She said: “It was really surprising that these individuals had completely different mutations causing their condition, especially because it’s so rare.”

Professor Eileen Murphy, Queen’s University Belfast, said: “We made several assumptions about these two men when we first realised that they both had suffered from multiple osteochondromas. We assumed they were contemporary but radiocarbon dating showed they were separated by several hundred years. We also assumed they were related but the new aDNA analysis has demonstrated that this is not the case.”

Professor Dan Bradley, from Trinity’s School of Genetics and Microbiology, said: “Discovery of the mutations that cause serious diseases through application of whole genome sequencing has been a key medical breakthrough in recent years, but this is the first time this has been applied to ancient individuals. The study demonstrates the important contribution that ancient DNA analysis on people from the past can make to understanding conditions that still affect people today.”

This work was funded by the Wellcome Trust and the Science Foundation Ireland Centre for Research Training in Genomics and Data Science.