Medieval Skeleton DNA Reveals XXY Chromosome Condition, Klinefelter Syndrome

When Portuguese archaeologists unearthed the skeleton of a remarkably tall man who lived over 1,000 years ago, they assumed he was too tall to be a local.

Standing about 1.8 meters tall, he would have been about a head taller than other adults of the time.

But DNA extracted from his bones revealed not only that he was from the area, but that he was also born with a genetic condition known as Klinefelter syndrome.

People with the condition are born with an extra X chromosome and tend to be taller than average.

It affects one or two people in 1,000 male births today.

The diagnosis by researchers in Portugal and Australia was reported in The Lancet.

João Teixeira, ancient DNA and evolutionary biologist at the Australian National University and co-author of the study, said it was the oldest confirmed case of Klinefelter syndrome to date.

The individual was buried in an oval-shaped grave with his arms folded across his chest.(Provided by: Sofia Tereso)

“We are interested in developing this [technique] further and applying it to other archaeological specimens to find not only cases of Klinefelter syndrome, but also other [conditions like it].

“That might give us an idea of ​​how common these genetic conditions are over time.”

Site of historical significance

The sculptural skeleton was one of several dozen discovered at the mountainous medieval archaeological site of Torre Velha in northeastern Portugal between 2012 and 2015.

In Roman times it was the site of a settlement located at the junction of the roads connecting the cities of the Iberian Peninsula.

“We are interested in looking at this place because of all the different peoples who have inhabited it, and understanding the different migrations of people, from the Romans to the Germanic tribes to the settlement of Portugal,” Dr Teixeira said.

When the people’s remains were discovered, they were carbon dated to find out when they died, and their DNA was extracted and sequenced.

DNA analysis on ancient specimens is not always possible. Long strands of DNA, which are twisted like chromosomes in our cells, tend to fall apart and be cut up by bacteria after we die.

Sometimes there just aren’t enough long strands left to get meaningful information.

Yet thousands of years old DNA can provide a wealth of information about a person, such as their ancestry and biological sex.

Biological sex is determined by our sex chromosomes, which are of two types: X and Y. We generally inherit an X from our mother and an X or a Y from our father.

Genetic females are usually XX while males are XY.

When Dr. Teixeira and his colleagues examined the DNA of the largest skeleton from Torre Velha, which was thought to be male because of the shape of the bones, they found something unexpected.

“The amount of DNA fragments mapped to the X chromosome was consistent with a female, but then we had as much mapping to the Y as you have for males,” Dr Teixeira said.

Statistically, the individual was virtually confirmed to be XXY – Klinefelter syndrome. This happens when an egg or sperm contains an extra X chromosome.

And when Dr. Teixeira’s colleagues took a close look at the skeleton, they could also see signs of the disease in the bones.

First, the height of the individual stood out, Dr Teixeira said, “and 1,000 years ago, 1.8m was really tall”.

The skeleton also showed other potential Klinefelter symptoms, such as wider-than-usual hips and more protruding teeth on one side than the other, possibly because the person had an underbite.

    A front and side view of a human skull.  He is missing front teeth and has an underbite
The well-preserved skull showed symptoms related to the teeth and jaw that could be caused by Klinefelter syndrome.(Provided: The Lancet)

The bigger picture

Matching genetic findings with skeletal evidence bolsters the study’s findings, according to Sally Wasef, who works with ancient DNA at Queensland University of Technology and was not involved in the work.

“It’s really interesting to be able to tell from ancient DNA whether or not a medical condition exists,” Dr Wasef said.

“But without [archaeological evidence]you’re just looking at one piece of a puzzle and trying to figure out what the whole picture looks like.”

Dr Teixeira said the technique could be used to glean information about extra or missing chromosomes in situations where DNA samples have been degraded, such as forensic investigations.

It could also be used to look for genetic conditions such as Down syndrome, which is caused by the presence of an extra copy of chromosome 21, throughout human history.

And as to how far they could go back?

It depends on the quality of the DNA. If a specimen is left undisturbed in the frozen Arctic, its DNA will be in much better shape than one in the hot, humid tropics.

“But if you find a really well-preserved specimen from 30,000 years ago, I think you could,” Dr Teixeira said.

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