DNA from a medieval skeleton in Portugal reveals XXY chromosomes

This article was originally published by the Australian Broadcasting Cooperation (ABC). We have reposted it here in its entirety to allow access for non-Australians and also to preserve information specific to the community.

When Portuguese archaeologists unearthed the skeleton of a remarkably tall man who lived more than 1,000 years ago, they assumed he was too tall to be a local.

Standing around 1.8 metres, he would have been around a head taller than other adults of the time.

But DNA extracted from his bones revealed not only was he from the region, he was also born with a genetic condition known as Klinefelter syndrome.

Those with the condition are born with an extra X chromosome and tend to be taller than average.

It affects one in 600 male births today.

The diagnosis by researchers in Portugal and Australia was reported in The Lancet.

João Teixeira, ancient DNA and evolutionary biologist at the Australian National University and co-author of the study, said it was the oldest confirmed case of Klinefelter syndrome so far.

Key points:

  • Researchers analysed the DNA and bones of a 1,000-year-old skeleton excavated from modern-day Portugal 
  • They found the individual had a genetic condition which meant they were born with an extra X chromosome
  • The diagnosis explains some of the skeleton’s features, such as its unusual height and wide pelvis
The individual was buried in an oval-shaped grave with arms crossed over their chest (Supplied Sophia Tereso)

“We’re interested in developing this [technique] further and applying it to other archaeological specimens to look not only for Klinefelter syndrome cases, but also other [conditions like it].

“This could help give us an idea about the frequency of these genetic conditions through time.”

Site of historical importance

The statuesque skeleton was one of a few dozen excavated from the mountainous medieval archaeological site of Torre Velha in north-eastern Portugal, between 2012 and 2015.

In Roman times, it was the site of a settlement that sat at the junction of roads connecting cities across the Iberian Peninsula.

“We’re interested in looking at this place because of all the different peoples that inhabited it, and to understand the different migrations of people, from the Romans to the Germanic tribes to the establishment of Portugal,” Dr Teixeira said.

When people’s remains were discovered, they were carbon-dated to find out when they died, and their DNA extracted and sequenced.

DNA analysis on ancient specimens isn’t always possible. Long strands of DNA, which are twisted up as chromosomes in our cells, tend to fall apart and get chopped up by bacteria after we die.

Sometimes there are simply not enough long strands left to elicit much meaningful information.

Still, DNA that’s thousands of years old can yield a wealth of information about a person, such as their ancestry and biological sex.

Biological sex is determined by our sex chromosomes, which come in two types: X and Y. We usually inherit an X from our mother or an X or Y from our father.

Genetic females are typically XX while males are XY.

When Dr Teixeira and his colleagues scrutinised DNA from the tallest Torre Velha skeleton, which was thought male from the shape of the bones, they found something unexpected.

“The amount of DNA fragments mapping to the X chromosome was compatible with a female, but then we had as much mapping to the Y as you have for males,” Dr Teixeira said.

“We were intrigued.”

Statistically, the individual was all but confirmed to be XXY — Klinefelter syndrome. This happens when an egg or a sperm contains an extra X chromosome.

And when Dr Teixeira’s colleagues closely examined the skeleton, they could see signs of the condition in the bones too.

First up, the individual’s height stood out, Dr Teixeira said, “and 1,000 years ago, 1.8m was seriously tall”.

The skeleton also had other potential Klinefelter symptoms such as broader-than-usual hips, and teeth that were worn more on one side than the other, perhaps because the person had an underbite.

The bigger picture

Pairing genetic findings with skeletal evidence strengthens the study’s findings, according to Sally Wasef, who works with ancient DNA at Queensland University of Technology and was not involved with the work.

“It’s really interesting that you can tell, from ancient DNA, the existence or not of a medical condition,” Dr Wasef said.

“But without [archaeological evidence], you’re only looking at a single piece of a puzzle, and trying to work out what the whole picture looks like.”

Dr Teixeira said the technique could be used to glean information about extra or missing chromosomes in situations where DNA samples were degraded, such as forensic investigations.

It could also be used to look for genetic conditions such as Down syndrome, which is caused by the presence of an extra copy of chromosome 21, through human history.

And as for how far back they could go?

That depends on the quality of the DNA. If a specimen is left undisturbed in the frozen Arctic, its DNA will be in much better shape than another in the hot, humid tropics.

“But if you find a really well-preserved specimen from 30,000 years ago, I think you could do it,” Dr Teixeira said.

Sourced from ABC (Australia)

New DNA ‘clock’ could help measure development in young children

Scientists have developed a molecular “clock” that could reshape how paediatricians measure and monitor childhood growth and potentially allow for an earlier diagnosis of life-altering development disorders.

The research, published this week in PNAS, (Full Study) describes how the addition of chemical tags to DNA over time can potentially be used to screen for developmental differences and health problems in children.

The study was led by researchers at BC Children’s Hospital, the University of British Columbia (UBC) and the University of California, Los Angeles. It is the first study to describe a method specifically designed for children, called the Paediatric-Buccal-Epigenetic (PedBE) clock, which measures chemical changes to determine the biological age of a child’s DNA.

Small chemical changes to DNA, known as epigenetic changes, alter how genes are expressed in certain tissues and cells. Some of these changes happen as a person ages and others may be in response to a person’s environment or life experiences.

Steve Horvath presents research on: Universal Epigenetic Aging Clock

In adults, these patterns of epigenetic changes are well established. They can be used to accurately predict a person’s age from a DNA sample or, if a person’s epigenetic age differs from their actual age, it can point differences in health, including age-related diseases and early mortality.

“We have a good idea how these DNA changes occur in adults, but until now we didn’t have a tool that was specific for children,” says Dr. Michael Kobor, senior author of study. “These DNA changes occur at very different rates in kids and so we adapted this technique for younger ages.”

“This powerful and easy-to-use tool could be used by clinicians to identify why some children aren’t meeting early milestones and potentially diagnose children with developmental disorders earlier in life, this would enable doctors and paediatricians to intervene sooner in a child’s life leading to better outcomes for kids.”

Dr. Lisa McEwen, first author on the study

Kobor is an investigator at BC Children’s Hospital and the Centre for Molecular Medicine and Therapeutics, a professor in the Department of Medical Genetics at the University of British Columbia, the Tier 1 Canada Research Chair in Social Epigenetics and the Sunny Hill BC Leadership Chair in Child Development.

The PedBE clock was developed using DNA methylation profiles from 1,032 healthy children whose ages ranged from a few weeks old to 20 years. The researchers found 94 different sites in the genome that, when tested together, could accurately predict a child’s age to within about four months. The team also found that children who spent longer in the womb showed an accelerated rate of DNA change by three months, demonstrating that this tool could be used to indicate an infant’s developmental stage. The analysis can be done cheaply and efficiently on cells collected from a cheek swab.

Continue reading…….

The Genetic Origins of Sex Differences in Disease

It took almost 15 years for scientists to sequence and publish a complete accounting of the human genetic code — the 3 billion base pairs along the double strands of DNA that serve as a blueprint for the body’s functions and pass traits from parents to offspring.

Now, approximately 15 years after the human genome was first sequenced, current discoveries represent just the beginning when it comes to the genetic origins of disease and the ever-expanding number of individual human genome sequences available to study. Researchers currently utilize what are called genome-wide association studies (GWAS) to discover hundreds of associations between genetic variations and specific diseases and disorders shared among individuals. But to date, very few researchers have fully explored how correlations between genes and disease may be different in women and men.

Few researchers have explored how genes, diseases, and biological sex interact.

Dr. Hongyu Zhao, an internationally known expert in the field of statistical genetics, has collected preliminary data to suggest that genetic pathways may relate to some diseases differently in women and men.

“Many human traits and diseases have sex or gender differences, and many diseases have a significant genetic component,” said Zhao, Department Chair and Ira V. Hiscock Professor of Biostatistics at Yale School of Medicine. “However, most analyses of genetic data assume the same effect for both women and men or use a methodology that is not calibrated to detect potential sex differences.”

Continue reading……