Medieval skeletons help reveal genetic causes of bone tumors -

Medieval skeletons help reveal genetic causes of bone tumors –

Two men buried in a medieval cemetery in Ireland suffered from a genetic condition called multiple osteochondromas, which causes benign bone tumors. One of the disease mutations is a new discovery, so this is the first time such insights have been unlocked from ancient genomic data.

In 2003, a cemetery was discovered in Ballyhanna, which is located in the northern part of Ireland. Archaeologists spent a few years uncovering the tombs, finding 1,296 people who were buried between the 7th and 17th centuries. Many of these people had high levels of skeletal indicators of stress, poor health, and infectious diseases such as tuberculosis.

The land would have belonged to the church at this time and the medieval Gaelic population would have included sharecroppers, labourers, merchants, craftsmen, clergy and the very poor. Applying ancient DNA analysis to the people of Ballyhanna has allowed us to build on previous osteoarchaeological research.

Life was particularly difficult for two men whose bones had multiple tumors resulting from a genetic condition called multiple osteochondromas. This condition is rare, can be extremely painful, and can lead to limb deformity, reduced height, 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, called Sk331 and Sk197. They lived a hundred years apart, as the article explains:

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

The researchers analyzed the genome sequences of the two affected skeletons and identified 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. This is the first time that a new pathological mutation has been discovered in old genomic data.

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

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

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

“We made several assumptions about these two men when we realized they both had multiple osteochondromas,” noted Professor Eileen Murphy of Queen’s University Belfast. “We assumed they were contemporaneous, but radiocarbon dating showed they were several hundred years apart. We also assumed they were related, but the new DNA analysis demonstrated that this it’s not the case.

This study represents another example of researchers being able to use genome sequencing to better understand disease. Other studies have looked at diseases such as brucellosis, lurch and Meadow. Professor Dan Bradley, of Trinity’s School of Genetics and Microbiology, adds that “Discovering the mutations that cause serious disease through the 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 analyzing ancient DNA on people from the past can make to understanding the conditions that still affect people today.” 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 via BioRxiv.

See also the Ballyhanna Research Project

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