Scientists have diagnosed Down syndrome from DNA in the ancient bones of seven babies, one up to 5,500 years old. Their method, published in the journal Nature Communications, may help researchers learn more about how prehistoric societies treated people with Down syndrome and other rare conditions.
Down syndrome, which affects 1 in 700 babies today, is caused by an extra copy of chromosome 21. The extra chromosome makes extra proteins, which can cause a range of changes, including heart defects and learning disabilities.
Scientists tried to find the history of the condition. Today, older mothers are more likely to have a child with the condition. In the past, however, women would have been more likely to die young, which may have made Down syndrome rarer, and children born with it would have been less likely to survive without heart surgery and other life-prolonging treatments them today.
Archaeologists can identify some rare conditions, such as dwarfism, from bones alone. But Down syndrome – also known as trisomy 21 – is a highly variable disease.
People with it can have different combinations of symptoms and can have severe or milder forms. Those with the characteristic almond-shaped eyes caused by Down syndrome may have relatively normal skeletons, for example.
As a result, it is difficult for archaeologists to confidently diagnose ancient skeletons with Down syndrome. “You can’t say, ‘Oh, this change is there, so it’s trisomy 21,'” said Dr. Julia Gresky, an anthropologist at the German Archaeological Institute in Berlin who was not involved in the new study.
In contrast, Down syndrome is not difficult to identify genetically, at least in living people. In recent years, geneticists have been testing their methods on DNA preserved in ancient bones.
However, it has been difficult because scientists cannot simply measure complete chromosomes, which fall apart after death into fragments.
In 2020, Lara Cassidy, then a geneticist at Trinity College Dublin, and her colleagues used ancient DNA for the first time to diagnose a baby with Down syndrome. They were examining genes from skeletons buried in a 5,500-year-old grave in western Ireland. The bones of a 6-month-old boy contained unusually high amounts of DNA from chromosome 21.
Since then, Adam Rohrlach, then a statistician at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and his colleagues developed a new method to find the genetic signature, which they can use to quickly examine thousands of bones.
The idea came to Dr. Rohrlach when he spoke with a scientist at the institute about his procedures for searching for ancient DNA. Because high-quality DNA sequencing is very expensive, it turned out that the researchers examined the bones with an inexpensive test, called shotgun sequencing, before selecting a few for further investigation.
If the bone still retained DNA, the test showed many tiny genetic fragments. Very often, these came from microbes that grow on bones after death. But some bones also contained DNA that was recognizably human, and those with a high percentage were flagged for additional testing.
Dr. Rohrlach learned that the institute had examined nearly 10,000 human bones in this way, and the results of all the shotgun sequences were stored in a database. It occurred to Dr. Rohrlach and his colleagues that they could scan the database for additional chromosomes.
“We thought, ‘No one has ever checked for this kind of thing,'” Dr. Rohrlach said.
He and his colleagues wrote a program that sorted fragments of the recovered DNA by chromosome. The program compared the DNA from each bone to the entire set of samples. He then identified specific bones that had an unusual number of sequences that came from a particular chromosome.
Two days after their initial conversation, the computer had their results. “It turned out our hunch was right,” said Dr Rohrlach, who is now an associate lecturer at the University of Adelaide in Australia.
They discovered that the institute’s collection included six bones with extra DNA from chromosome 21 – the signature of Down syndrome. Three belonged to babies as young as one year old and the other three to fetuses that died before birth.
Dr. Rohrlach also attended Dr. Cassidy in 2020. He used his program to sequence the shotgun for the Irish skeleton and found that she also had an extra chromosome 21, confirming her original diagnosis.
In addition, Dr. Rohrlach found another skeleton with an extra copy of chromosome 18. This mutation causes a condition called Edwards syndrome, which usually results in death before birth. The bones came from an unborn fetus that had died at 40 weeks and was severely deformed.
The new research does not let Dr. Rohrlach and his colleagues determine how common Down syndrome was in the past. Many children with the condition likely died before adulthood, and children’s fragile bones are less likely to be preserved.
“There is so much uncertainty in sampling and what we could and couldn’t find,” Dr Rohrlach said. “I think it would be a very brave statistician to try to make too much of these numbers.”
But Dr Rohrlach found it significant that three children with Down syndrome and one with Edward syndrome were buried in two neighboring towns in northern Spain between 2,800 and 2,400 years ago.
Normally, people in this culture were cremated after death, but these children were buried inside buildings, sometimes with jewelry. “They were special babies being buried in these houses, for reasons we just don’t understand yet,” Dr. Rohrlach speculated.
Dr. Gresky did not believe that the evidence made it possible to rule out the possibility for all cases.
“Maybe the bones there were so well preserved,” he said. “Maybe the archaeologists were so good and well trained that they took them all out. Maybe they were buried in a way that made it easier to find them.”
Still, Dr. Gresky considered the new study a significant advance. First, it may allow archaeologists to compare remains genetically identified with Down syndrome and discover some hidden features common to all their skeletons.
And Dr Gresky hoped other researchers would use the ancient DNA to illuminate the hidden histories of other rare diseases: “You just have to look for them and talk about them. Otherwise, they will remain invisible.”
