Researchers Mute Extra Chromosome Responsible for Down Syndrome
July 18, 2013 12:25 PM
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The team used an RNA gene called XIST
Researchers have found a way to mute an extra chromosome known for causing trisomy 21, or Down syndrome.
Scientists at UMass Medical School -- led by Jeanne B. Lawrence, PhD, professor of cell & developmental biology -- have used an RNA gene to hush the chromosome responsible for Down syndrome, which could open new possibilities for studying the condition.
People with Down syndrome have three copies of chromosome 21 instead of two, causing trisomy 21. This leads to cognitive disability and early-onset
. It can also cause other complications, such as heart defects.
The team used an RNA gene called XIST -- which typically silences one of the X chromosomes found in females -- as inspiration for the study. The large XIST RNA is created during early development from one of the two X chromosomes in the female, and has the ability to prevent the X chromosome's DNA from being expressed to produce proteins. This makes the genes on the chromosome silent.
Using this idea, the team collected induced pluripotent stem cells from fibroblast cells donated by a Down syndrome patient. The researchers then used zinc finger nuclease (ZFN) technology to place the XIST gene in the extra chromosome 21.
The results showed that the XIST RNA
successfully muted genes
across the extra chromosome and stopped it from working. Gene expression levels returned to a more normal state from there.
It also showed that XIST is capable of reversing the problems with cell proliferation and neural cell differentiation found in Down syndrome cells.
“In the short term the correction of Down syndrome cells in culture accelerates the study of cell pathology and translational research into therapeutics, but also for the longer-term, potential development of ‘chromosome therapies,’ which utilize epigenetic strategies to regulate chromosomes, is now at least conceivable," said Lawrence.
"Since therapeutic strategies for common chromosomal abnormalities like Down syndrome have received too little attention for too long, for the sake of millions of patients and their families across the U.S. and the world, we ought to try."
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