Scientists diagnosed Down syndrome based on DNA from the ancient bones of seven babies, one of them
from 5,500 years ago
.
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 diseases.
Down syndrome, which occurs in
1 in 700 babies
today, is caused by an extra copy of chromosome 21. The extra chromosome produces an excess of stem cells.
The extra chromosome produces additional proteins that can cause a series of disorders, such as heart defects and learning difficulties.
Scientists struggled to unravel the history of this disease.
Today,
older mothers
are the most likely to have a child with this condition.
In the past, however, women were more likely to die young, which could have made Down syndrome rarer, and children born with it would have been
less likely to survive
without heart surgery and other treatments that prolong their lives. lives today.
Archaeologists can identify some rare diseases, such as dwarfism, from bones alone.
But Down syndrome - also known as trisomy 21 - is a very variable disease.
People who suffer from it can present different combinations of symptoms and have severe or milder forms.
For example, people with the characteristic almond-shaped eyes of Down syndrome may have a relatively normal skeleton.
Older mothers are more likely to have a child with Down syndrome.
Photo: Shutterstock
This makes it
difficult for archaeologists to confidently diagnose
ancient skeletons with Down syndrome.
"You can't say, 'This change is there, so it's trisomy 21,'" says Julia Gresky, an anthropologist at the German Archaeological Institute in Berlin who was not involved in the new study.
On the other hand, it is not difficult to genetically identify Down syndrome, at least in living people.
In recent years, geneticists have tested their methods on
DNA preserved in ancient bones
.
However, it was a challenge, because scientists cannot simply count entire chromosomes, which break up into fragments after death.
In 2020, Lara Cassidy, a geneticist at Trinity College Dublin, and her colleagues for the first time used ancient DNA to diagnose a baby with Down syndrome.
They examined 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 chromosome 21 DNA.
Since then, Adam Rohrlach, a statistician at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and his colleagues developed a new method for
finding the genetic signature
, allowing them to quickly analyze thousands of bones.
The path to the "genetic signature"
The idea came to Rohrlach when he spoke with a scientist at the institute about their procedures for searching for ancient DNA.
Because high-quality DNA sequencing is very expensive, researchers examined the bones with a cheap test, called shotgun sequencing, before selecting a few for further investigation.
If the bone still had DNA, the test showed many tiny genetic fragments.
They often came from microbes that grow in bones after death.
But some bones also contained DNA recognizable as human, and those with a high percentage were flagged for further testing.
Rohrlach learned that the institute had analyzed
almost 10,000 human bones in this way
, and the results of all the shotgun sequences were stored in a database.
It occurred to Rohrlach and his colleagues that they could scan the database for additional chromosomes.
"We thought, 'No one ever looked for this kind of thing,'" Rohrlach explains.
Rohrlach and his colleagues wrote a program that sorted the recovered DNA fragments by chromosome.
The program compared the DNA from each bone to the entire set of samples.
He then identified bones that had an unusual number of sequences from a specific chromosome.
The first results
Two days after their initial conversation,
the computer had the results
.
"It turned out that our hunch was right," says Rohrlach, who is now an associate professor 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 barely one year old and the other three to fetuses that died before birth.
Rohrlach also followed up on Cassidy's 2020 study. He used his program to analyze the shotgun sequence of the Irish skeleton and found that it also had an extra chromosome 21, confirming his initial diagnosis.
Additionally, Rohrlach found another skeleton with an extra copy of chromosome 18. This mutation causes Edwards syndrome, which usually causes death before birth.
The bones came from a fetus that had died at 40 weeks and were severely deformed.
The new study does not allow Rohrlach and his colleagues to determine how common Down syndrome was in the past.
Many children with this condition probably died before adulthood, and children's brittle bones are less likely to be preserved.
"There's a lot of uncertainty in sampling and what we could and couldn't find," Rohrlach said.
"I think it would be a very brave statistician to try to draw too many conclusions from these figures."
But Rohrlach did find it significant that three children with Down syndrome and one with Edwards syndrome were buried in two neighboring cities in northern Spain between 2,800 and 2,400 years ago.
Normally, people from that culture were cremated after their death, but these children
were buried inside buildings, sometimes with jewelry
.
"They were special babies who were buried in these houses, for reasons we still don't understand," Rohrlach speculated.
Gresky did not believe that the tests allowed us to rule out chance as the cause of the cluster of cases.
"The bones may have been so well preserved," he said.
"Maybe the archaeologists were so good and well trained that they dug them all up. Maybe they were buried in a way that made them much easier to find."
Still, Gresky considered the new study an important advance.
On the one hand, it could allow archaeologists to compare remains genetically identified as having Down syndrome and discover some hidden set of traits common to all their skeletons.
And Gresky hoped other researchers would use ancient DNA to illuminate the hidden stories of other rare conditions.
"You have to look for them and you have to talk about them," Gresky said.
"Otherwise, they will remain invisible."
The New York Times. Special
Translation: Patricia Sar
P.S.