Prenatal Testing and the Future of Down Syndrome
2,500-year-old Skeletons Reveal Familiar Genetic Conditions In The Iron Age, Study Says
Researchers in the United Kingdom have discovered a way to identify genetic conditions in people who lived thousands of years ago.
In a new study, published Jan. 11 in the journal Communications Biology, researchers found sex-chromosome syndromes in DNA from six ancient skeletons unearthed in Britain.
"In our study … we reconstruct the profiles of 6 individuals with aneuploidy (additional or missing chromosomes in their karyotype) from ancient Britain," Kakia Anastasiadou, a researcher in the study, said in a post on X, formerly known as Twitter.
Anastasiadou and her colleagues at the Francis Crick Institute in London examined the DNA from these ancient people and found the presence of four familiar conditions: Down syndrome, Turner syndrome, Jacob's syndrome and Klinefelter syndrome.
Human cells have 23 pairs of DNA molecules, called chromosomes. Sex chromosomes are typically XX for females and XY for males.
Sex-chromosomal conditions occur when a person's cells have either an extra or missing chromosome. When this happens, we often see characteristics like different behavior, delayed development or variations in appearance.
Using a new computational method, the researchers said they were able to measure the number of chromosomes by counting the copies of X and Y chromosomes and comparing the resulting number to a predicted baseline.
With this method, the group identified the first prehistoric person with Turner syndrome (a female with only one X chromosome instead of two) from about 2,500 years ago, according to the study.
They also identified the first person with Jacob's syndrome (a male with an extra Y chromosome — XYY), a baby with Down syndrome (an extra chromosome) from the Iron Age and three people with Klinefelter syndrome (males with an extra X chromosome — XXY) from several different time periods, researchers said.
Their findings straddle medicine and archaeology.
"We hope this will contribute information for archaeologists to understand past societies, and a historical perspective for present-day patients and clinicians," Pontus Skoglund, a researcher in the study, said in a post on X.
From this study, experts may get a clearer picture of how these conditions existed in the population over time, and how societies responded to them.
"The more studies like this are done, the better we can explore how past societies viewed sex and gender, or in the case of certain (genetic syndromes), how disability may have been understood in the past," archaeologist Ulla Moilanen told Nature.
The group's findings could give experts a view into the way older societies treated sex and differences, according to the study. Their methods could also open the door for experts to discover more about ancient peoples and customs.
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Using FISH To Detect Chromosomal Abnormalities In Interphase Nuclei.
Using FISH to detect chromosomal abnormalities in interphase nuclei.
(a) The duplication of a small portion of chromosome 17 that causes Charcot-Marie-Tooth syndrome is evident from the appearance of three, rather than two, red signals in this nucleus. The green spots mark a sequence outside the duplication. (b) The translocation that creates a fusion of the BCR (on chromosome 22) and ABL (on chromosome 9) genes in the Philadelphia chromosome is evident from the close juxtaposition of one pair of green and red signals. These signals were generated using FISH probes for sequences located near these two genes, respectively. Der(22) is the Philadelphia chromosome. Only the relevant portions of the normal and abnormal chromosomes are shown in the diagram below each panel.
Cytogeneticists can now go "FISH-ing" for chromosomal abnormalities, which are deletions and duplications that can cause disease. How exactly does FISH work?
Gene Dyrk1a Linked To Heart Defects In Down Syndrome Identified
Leveraging genetic mapping, scientists pinpointed a gene on human chromosome 21 named Dyrk1a. In the mouse model of Down syndrome, having three copies of this gene leads to heart defects. While Dyrk1a has been associated with cognitive impairment and facial changes in Down syndrome, its involvement in heart development was previously unknown. (1✔ ✔Trusted SourceIncreased dosage of DYRK1A leads to congenital heart defects in a mouse model of Down syndromeGo to source) Down syndrome affects around 1 in 800 new births and is caused by an extra third copy of chromosome 21. About half of babies born with Down syndrome have heart defects, such as a failure of the heart to separate into four chambers, leaving a 'hole in the heart'. 'Scientists pinpointed the gene Dyrk1a as the cause of heart defects in Down syndrome, a condition resulting from an extra copy of chromosome 21. #Downsyndrome #genetics #heartdefects ' If the heart defects are very serious, high-risk surgery might be needed soon after birth and people often require ongoing monitoring of the heart for the rest of their life. Therefore, better treatment options are needed and this must be guided by knowledge of which of the extra 230 genes on chromosome 21 are responsible for the heart defects. But before this study the identity of these causative genes was not known.In research published today in Science Translational Medicine, the team at the Crick and UCL studied human Down syndrome fetal hearts as well as embryonic hearts from a mouse model of Down syndrome.
An extra copy of Dyrk1a turned down the activity of genes required for cell division in the developing heart and the function of the mitochondria, which produce energy for the cells. These changes correlated with a failure to correctly separate the chambers of the heart.
The team found that while Dyrk1a is required in three copies to cause heart defects in mice, it was not sufficient alone. Thus, another unknown gene must also be involved in the origin of heart defects in Down syndrome. The team is currently searching for this second gene. Dyrk1a codes for an enzyme called DYRK1A. The researchers tested a DYRK1A inhibitor on mice pregnant with pups that model the hearts defects in Down syndrome, as their hearts were forming. When DYRK1A was inhibited, the genetic changes were partially reversed and the heart defects in the pups were less severe.Victor Tybulewicz, Group Leader of the Immune Cell Biology Laboratory & Down Syndrome Laboratory, said: "Our research shows that inhibiting DYRK1A can partially reverse changes in mouse hearts, suggesting that this may be a useful therapeutic approach.
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"However, in humans the heart forms in the first 8 weeks of pregnancy, likely before a baby could be screened for Down syndrome, so this would be too early for treatment. The hope is that a DYRK1A inhibitor could have an effect on the heart later in pregnancy, or even better after birth. These are possibilities we are currently investigating."This research forms part of the lab's overall goal to understand the genetics behind all aspects of Down syndrome.
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Eva Lana-Elola, Principal Laboratory Research Scientist at the Crick, and co-first author, said: "It was remarkable that just restoring the copy number of one gene from 3 to 2 reversed the heart defects in the mouse model for Down syndrome. We're now aiming to understand which of the other genes on this extra chromosome are involved. Even though Dyrk1a isn't the only gene involved, it's clearly a major player in many different aspects of Down syndrome."Rifdat Aoidi, Postdoctoral Project Research Scientist at the Crick, and co-first author, said: "We don't yet know why the changes in cell division and mitochondria mean the heart can't correctly form chambers. Dysfunction in the mitochondria has also been linked to cognitive impairment in Down syndrome, so boosting mitochondrial function could be another promising avenue for therapy."
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