Findings from a study published in the journal Nature Communications have showcased how DNA from the skeletal remains of seven infants, the oldest of which dated back 5,500 years, was used by scientists to diagnose Down syndrome. This new technique could prove insightful in helping scientists understand how prehistoric societies perceived and treated individuals with Down syndrome, along with other rare disorders.
Down syndrome, also known as trisomy 21, affects one in every 444 newborns in Ireland, and is the result of an additional copy of chromosome 21. This surplus chromosome produces an excess of proteins that can result in various physiological changes, such as learning difficulties and heart problems.
The historical context of Down syndrome continues to perplex scientists. Today, it is older mothers who are the most likely to give birth to a child with Down syndrome. However, in earlier times, younger women were more likely to have a successful childbirth as they had a higher survival rate, which perhaps made the occurrence of Down syndrome rarer. Additionally, without the modern-day medical treatments such as heart surgeries, infant survival rates would have been lower.
Some rare disorders like dwarfism can be identified by archaeologists simply by examining skeletal remains, but because Down syndrome symptoms can range widely in severity and form, confirmation of ancient cases of Down syndrome remains a challenge. However, identifying Down syndrome genomically has been possible in living individuals.
Recently, scientists have been trying to apply genomic testing techniques to the DNA preserved in ancient bones, but have faced obstacles due to the decomposition of whole chromosomes into fragments after death.
Despite these challenges, in 2020, Lara Cassidy, a geneticist at Trinity College Dublin at the time, along with her team utilised ancient DNA for the first time to diagnose Down syndrome in a baby. This reveal came about whilst researching genes from skeletons found in a 5,500-year-old tomb in western Ireland, where they noticed unusually high amounts of DNA from chromosome 21 in the bones of a six-month-old boy.
Adam Rohrlach, previously a statistician at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, along with his teammates created a unique technique to rapidly identify genetic signatures amongst countless bones. Rohrlach conceived this method after a discussion with a fellow institute scientist about the expensive process of high-quality DNA sequencing used in searching for ancient DNA.
To curtail expenses, the researchers implemented a cost-effective method known as shotgun sequencing to initially screen the bones before choosing a select few for intense study. If the bone still had preserved DNA, this test produced numerous minute genetic fragments, typically from microbes that inhabit bones post-mortem. Some bones, however, held recognisably human DNA, with these being selected for further testing if they displayed a significant amount.
Rohrlach discovered that nearly 10,000 human bones were screened at the institute using this method, and all the shotgun sequencing results were logged in a database. An idea occurred to Rohrlach and his team to use this database to scout for additional chromosomes. Noting that this had never been done, they developed a programme that sorted the DNA fragments by chromosomes and compared the DNA from each bone with all the samples. This process led them to locate specific bones with an unusual number of sequences originating from a certain chromosome.
In just two days following their initial discussion, the computer produced their findings. Rohrlach, currently an associate lecturer at the University of Adelaide in Australia, revealed their supposition was correct. Their search led them to six bones in the institute’s collection with surplus DNA from chromosome 21, indicative of Down syndrome. Among them, three were traced to infants up to a year old, while the rest were linked to pre-born foetuses.
Rohrlach utilized his programme to evaluate the shotgun sequencing for an Irish skeleton as a follow up to Cassidy’s 2020 study. The skeleton was also discovered to carry an extra chromosome 21, reinforcing her initial diagnosis.
Rohrlach uncovered another skeleton that contained an additional copy of chromosome 18, resulting in Edwards syndrome, a condition which commonly leads to fetal death before birth. The skeletal remains were from a fetus that passed away at 40 weeks.
Rohrlach and his team, however, cannot determine the prevalence of Down syndrome in the past through this study. It is likely that many children affected by the condition didn’t survive till adulthood and due to the fragile nature of children’s bones, preservation isn’t likely. The uncertainty in the sample and what could be inferred from it is large, as Rohrlach pointed out. He mentioned that any statistician who tried to draw a lot of conclusions from these numbers could be very audacious.
What Rohrlach found noteworthy was that the remains of three children with Down syndrome and one with Edwards syndrome were all discovered in two nearby cities in the northern part of Spain ranging from 2,800 to 2,400 years ago.
People from that era were usually cremated post mortem, but these children were laid to rest inside structures, sometimes adorned with jewellery. Rohrlach hypothesized that these particular infants were buried in these houses for reasons not yet understood. The source of this article was originally the New York Times.