Ancient DNA Reveals Down Syndrome in Historical Populations

Researchers from the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) have developed a method that integrates data from genetic screening, osteological and archeological analyses to explore trisomies in historic and prehistoric populations.

Trisomies are genetic disorders characterized by the presence of an additional chromosome in a person’s cells. Typically, each human has 23 pairs of chromosomes or 46 in total. Individuals with trisomies possess a total of 47.

By screening the genomes of ~10,000 ancient individuals, the research team identified genetic evidence for 6 cases of trisomy 21 – Down Syndrome – and 1 case of trisomy 18 – Edwards Syndrome – in infant remains that date back as far as 5,000 years ago.  

The study offers novel insights into how these genetic conditions were perceived in the past, as some of the children’s remains were accompanied by special objects, indicating they were loved and cherished, the authors said.

“I like that we can look back on the past and see a positive aspect of our ancestors, and hopefully see ourselves in that,” said Dr. Adam “Ben” Rohrlach, a mathematician with joint affiliations at the University of Adelaide and MPI-EVA, and first author of the study.

The research is published in Nature Communications.

The field of ancient DNA analysis is thriving

The number of studies analyzing ancient DNA (aDNA) has substantially increased since the field emerged in 1984. Large databases comprising thousands of genomes mean that, today, we know more about the origin of humans, the migration patterns of our ancestors and how they battled ancient epidemics than ever before.

Only recently has the data published by the field become so vast that researchers could use it to explore the incidence of uncommon conditions. Rohrlach and colleagues’ study is the first systematic genetic screening and osteological description of autosomal trisomies.

It’s perhaps a more unique application of aDNA analysis, but one that Rohrlach views as worthwhile: “We know more about diseases that have affected large groups of people, such as plague, but individual disease and disorder is more personal, because it potentially marks a single, specific person as ‘different’. So, I think we’re all interested in how our ancestors approached these situations,” he said. 

Down Syndrome in past societies

Sequencing data collected between 2016–2022 at MPI-EVA was screened for trisomy using the team’s new method. This approach can be applied to any laboratory’s data, Rohrlach explained: “Our method compares the amount of DNA in a sample that comes from each chromosome and compares it to the average that is observed in all of the other samples (looking for when a 50% increase is observed).”

Of the 9,855 prehistoric and historic genomes analyzed, 6 infants presented with a high number of DNA sequences from chromosome 21, indicating that they had Down Syndrome. While there isn’t a single bone marker available for trisomies, where possible, Rohrlach and team recorded pathological lesions from the skeletal remains of these children that were preserved. They observed porosity in the cranial bones for almost all samples. While this is sometimes seen in Down Syndrome, the researchers stress that it can also be caused by other health conditions.

Five of the children’s remains were found across Bronze Age settlement sites in Greece and Bulgaria, and Iron Age settlement sites in Spain. They are estimated to be 2,500–5,000 years old.

“All of the Bronze Age or Iron Age burials were intramural burials, indicating that these infants were considered worthy of deserving a burial place inside of the dwellings,” the authors said.

One child, buried in Lazarides in Greece, wore a necklace made up of different colored beads. Another, in Spain, was surrounded by the complete remains of sheep and goats. Her grave also featured bronze rings and a Mediterranean seashell.

The remaining child was buried in a former church graveyard in Finland between the 17^th and 18^th century. He was found in a wooden coffin, wearing clothes that contained bronze pins and decorative bronze flowers, a trend in this period.

“For us, we interpret this as an indication that these children were loved and cherished like any child today,” Rohrlach expressed. “I cannot imagine another reason that the baby at Lazarides was buried with a beautiful necklace. Unfortunately, we can’t know exactly.”

While advancements in medicine mean that people with Down Syndrome can live long, fulfilled lives, this wasn’t always the case historically. Combined evidence suggests that only two of the six children survived postnatally.

“These syndromes can cause a number of symptoms and complications which medicine at the time could not overcome,” Rohrlach said. “However, it is not clear how the children at the Iron Age sites were chosen for intramural burial, and the burials of many other children at these sites were found that did not indicate a diagnosis of trisomy 21. It is possible that these people were burying children if they were stillborn, and this would skew the number of perinatal cases.”

Edwards Syndrome in Iron Age Spain

Remains from a child with three copies of chromosome 18 were also identified at one the of the Spanish Iron Age sites. This is characteristic of Edwards Syndrome, a genetic condition that is rarer than Down Syndrome and affects the development of the brain and organs.

“At the moment, we cannot say why we find so many cases at these sites,” said Roberto Risch, an archeologist at the Autonomous University of Barcelona, and study co-author. “But we know that they belonged to the few children who received the privilege to be buried inside the houses after death. This already is a hint that they were perceived as special babies.”

Prevalence rates for autosomal trisomies were historically lower than current rates, according to the study. There are many factors that likely contribute to this finding, according to Rohrlach: “One could be that we know from modern cases that an increase in the rate of prevalence is correlated with an increase in the age of the mother, and potentially mothers were younger in past societies.”

Sampling bias might also play a role. Burials can be hard to find, and the easiest gravesites to miss are likely those belonging to younger individuals. In reality, the prevalence of autosomal trisomies might be higher than calculated in the study because these graves have not yet been discovered.

Refining aDNA screening methods to detect rare disorders

The team at MPI-EVA is keen for aDNA screening methods to be better refined, enabling more accurate detection of genetic conditions such as autosomal trisomies. “A complete extra copy of a chromosome is a very easy signal to observe,” Rohrlach said. “Other conditions are much more subtle and may only affect a part of the chromosome, or even a single gene. Hence, we need to develop and refine these methods to detect these more subtle variations that can still have significant effects.”

Unfortunately, the team was not able to access all of the skeletons from which the genetic data had been obtained, as they came from previous studies. “It would have been nice to have been able to revisit some more of the osteological questions that we had as this angle could have helped osteologist to flag potential cases in their records and museum collections,” Rohrlach said.

That being said, he ultimately “feels happy” that the research team were able to publish a study with a positive message. “I’m also proud that this study shows the potential of cross-disciplinary research, and how a mathematician, and computer scientist and an osteologist can come together to produce a meaningful narrative highlighting the lives of these babies, and those that were around them,” Rohrlach concluded.

Dr. Adam “Ben” Rohrlach was speaking to Molly Campbell, Senior Science Writer for Technology Networks.

About the interviewee:

Dr. Adam “Ben” Rohrlach is a postdoctoral researcher at the Max Planck Institute for the Science of Human History in Jena, Germany. His areas of interest are bioinformatics, phylogenetics, population genetics and biostatistics, with a focus on human history.

Reference: Rohrlach AB, Rivollat M, de-Miguel-Ibáñez P, et al. Cases of trisomy 21 and trisomy 18 among historic and prehistoric individuals discovered from ancient DNA. Nat Comms. 2024. doi: 10.1038/s41467-024-45438-1