The earliest recorded case of the genetic disease Klinefelter Syndrome has just been discovered – in a 1,000-year-old skeleton excavated from an archaeological site in Portugal.
Occurring in about one in every thousand male births, Klinefelter syndrome is a condition in which individuals are born with an extra copy of the X chromosome – resulting in an XXY combination.
Although it often causes no obvious symptoms (many cases are never diagnosed), men with the condition tend to be tall, with broad hips and sparse body hair. The condition is also associated with infertility, reduced sex drive and a slightly increased risk of type 2 diabetes.
This latest discovery will now help experts chart the spread of Klinefelter syndrome over the centuries.
A multidisciplinary approach encompassing genetic, statistical, archaeological and anthropological data is required to arrive at the diagnosis.
After the recovered skeleton was radiocarbon dated to the 11th century, the team undertook DNA analysis. Part of this analysis involved computational mapping of X and Y chromosome fragments to the reference human genome.
“We were immediately excited when we first looked at the results,” says evolutionary biologist Joao Teixeira of the Australian National University.
“However, ancient DNA is often degraded and of low quality and abundance, meaning we were initially cautious.”
Using a Bayesian inference model and an individualized approach, researchers were able to be more certain of their diagnosis by comparing their results to a theoretical XXY karyotype (a complete set of chromosomal information with the extra X).
In other words, probabilistic modeling was used to fill in some of the gaps in the DNA record, confirming that there is a different ratio of genes between those belonging to the Y and X chromosomes.
This same approach can be improved and extended to analyze DNA in other cases where only fragments are available, the researchers say, from modern crime scenes to archaeological digs.
“Given the fragile state of DNA, we developed a new statistical method that can take into account the characteristics of ancient DNA and our observations to confirm the diagnosis,” says Teixeira.
Observational skeletal examination also revealed features consistent with Klinefelter syndrome—including taller than average height, wider than average hips, and misalignment of the jaw and teeth.
The skeleton itself was well preserved, the researchers reported, taken from the Torre Velha site in northeastern Portugal. It probably belonged to an elderly man over 25 years old at the time of his death who was approximately 180 centimeters tall.
Although Klinefelter syndrome was originally identified in 1942, no ancient cases had been documented before then, making it easily the earliest case on record—and offering some clues to help experts better understand it.
The researchers want to emphasize how important it was to use different lines of evidence, using different fields of scientific research, to understand that this skeleton really came from a person with Klinefelter syndrome.
Thanks to the genetic analysis techniques scientists now have access to, ancient DNA is being used to make all kinds of discoveries: covering animal evolution, human history, the spread of disease, and much more.
“In recent years, ancient DNA has helped rewrite the history of the world’s human populations,” says paleogeneticist Bastien Lamas of the University of Adelaide in Australia.
“Our study shows that it is now a valuable resource for biomedical research and the growing field of evolutionary medicine.”
The study was published in The lancet.