Medieval skeletons help reveal genetic causes of bone tumours

Two men buried in a medieval graveyard in Ireland had a genetic condition called Multiple Osteochondromas, which causes benign bone tumours. One of the disease mutations is a new discovery, so this is the first time such information has been unlocked from ancient genomic data.

In 2003 a graveyard was discovered in Ballyhanna, which is located in the northern part of Ireland. Archaeologists spent a couple of years uncovering the graves, finding 1296 individuals who were buried between the 7th and 17th centuries. Many of these people showed high rates of skeletal indicators of stress and ill health and infectious diseases such as tuberculosis.


The land would have been owned by the church at that time and the Gaelic medieval population would have included tenant farmers, labourers, merchants, artisans, clergy and the very poor. The application of ancient DNA analysis to the people of Ballyhanna has enabled us to build upon earlier osteoarchaeological research.

Life was particularly challenging for two men whose bones showed multiple tumours resulting from a genetic disease called multiple osteochondromas. This condition is rare, can be extremely painful and can lead to limb deformity, reduced stature, nerve compression and, in ~ 5% of cases, malignancy.


In a study published in the European Journal of Human Genetics, researchers from Trinity College Dublin and Queen’s University Belfast examined these two individuals, who are termed Sk331 and Sk197. They lived hundred years apart, as the article explains:

Of the two, Sk331 lived more recently (dated AD 1031-1260) and was the more severe case. He displayed extensive bilateral osteochondromas, both sessile and pedunculated in form, on most bones throughout his skeleton. He also had a short stature compared to other adult males at Ballyhanna (158.3 cm), displayed a major deformity of his left forearm due to shortening of the ulna, had unequal bone lengths due to the lesions, as well as a range of orthopaedic deformities that affected his hips, knees and left ankle; all of which are consistent with this condition6. He died as a young adult (18-25 years). Sk197 was dated to AD 689-975 and was slightly older (30-40 years) when he died. While multiple osteochondromas were evident throughout his skeleton, they were generally less pronounced than those evident in Sk331. Limb length discrepancy was present in his forearm bones, his sacro-iliac joints displayed ankylosis and he would have had genu valgum during life. Unlike Sk331, he was estimated to have been of roughly average height for the population (166.8 cm). Neither individual appears to have suffered from any tumors that progressed to malignancy.

The researchers analysed genome sequences from the two affected skeletons and identifying mutations in a gene called EXT1, which is known to be involved in this disease 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. It represents the first time a new disease mutation has been discovered in ancient genomic data.

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

The right tibia and fibulas of one of the skeletons. Image courtesy Queen’s University Belfast.

The disease only occurs in 1 in 50,000 people and when it is found within a modern locality the affected people tend to be related. Here it is surprising that the same rare condition occurred twice in the same parish but resulted from two different mutations. In this case, the lightning of genetic tragedy struck twice.

“We made several assumptions about these two men when we first realised that they both had suffered from multiple osteochondromas,” noted Professor Eileen Murphy of Queen’s University Belfast. “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.”

This study represents another example of researchers being able to use genome sequencing to better understand diseases. Other studies have looked at diseases such as brucellosis, yaws and leprosy. Professor Dan Bradley, from Trinity’s School of Genetics and Microbiology, adds that “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.”


The article, “Millennium-old Pathogenic Mendelian Mutation Discovery for Multiple Osteochondromas from a Gaelic Medieval Graveyard,” by Iseult Jackson, Valeria Mattiangeli, Lara M Cassidy, Eileen Murphy and Daniel G Bradley, is published in the European Journal of Human Genetics. You can read it through BioRxiv.

See also the Ballyhanna Research Project