Scientists May Have Found A Genomic Off Switch For Down's Syndrome

One in every thousand or so babies born today will suffer from Down Syndrome, a genetic disorder caused by the presence of a third copy of chromosome 21 that results in learning disabilities, a heightened risk of bowel and blood diseases, and a severely heightened risk of dementia later in life. But a radical new genome treatment method could hold the key to turning off that extra chromosome 21 like a light.

Normally, every human carries 23 chromosome pairs which provide the genetic blueprint by which the body operates during its life. However, people with DS have either a partial or full extra copy of chromosome 21. This superfluous genetic data causes the symptoms commonly associated with the disease. However, a team of researchers from the University of Massachusetts led by Dr. Jeanne Lawrence have just published some exciting study results in the journal Nature suggesting a potent new treatment method for DS.

The UMass team employed a technique known as "genome editing" to inject the XIST gene into the extra chromosome of cells cultured from DS patients. XIST is a gene vital to embryonic development. It plays a major role in gender determination by silencing the second X chromosome thereby turning the foetus male (if it doesn't turn on, the second X chromosome remains active and the baby will be female). It's this genomic silencing ability that Lawrence's team exploited against chromosome 21.

After inserting XIST into the extra chromosome, the body coats and smothers it with RNA, effectively turning the chromosome off and halting the effects of its expressed genes. Individual cell cultures treated with this technique showed stronger, faster growth. Lawrence's team hopes that this breakthrough will someday help alleviate the early-onset dementia that some 60 per cent of DS patients suffer from by the time they hit 60 years. It could potentially -- and the possibility is very remote at this point -- eliminate the disease entirely through a prenatal gene therapy.

What's more, the technique has already shown promise with other similar diseases such as Edward syndrome (triplicated chromosome 18) and Patau syndrome (triplicated chromosome 13). As the Nature study exclaims, this "surmounts the major first step towards potential development of chromosome therapy".

It is not, however, the magic bullet science is looking for. "The long-range possibility -- and it's an uncertain possibility -- is a chromosome therapy for Down's syndrome," Lawrence explained to The Guardian. "But that is 10 years or more away. I don't want to get people's hopes up."

So before the medical community begins tinkering with people's genetic code, much more research has to be done. The next step is mouse model trials; injecting the XIST into early-stage embryonic mice to correct their cells. Beyond that, the research could hit a stumbling block in the ethical dilemma of whether or not to experiment on in vitro humans. On the other hand, 10 years is a long time and, given the rapid advancements of artificial cell organelles, we may be able to sidestep human experimentation altogether. [Guardian]

Picture: Denis Kuvaev / Shutterstock

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    That kid in the picture is cute. I hope she has a happy life.

    Wow, good news indeed and far more surprising is that the article was written by someone familiar with the concept of restraint, a rare thing in medical news

    Where does the paragraph on X chromosomes come into the case with DS....

    That would be in cases of Klinefelter syndrome (XXY) with a second X chromosome, that actually has nothing to do with down syndrome, the link isn't established in the article. (If it is just to turn off the X chromosome in a normal male (XY) then don't call it a second X chromosome, maybe edit as: the second sex chromosome (as in the other one is the Y chromosome.) Makes for a little confusing reading as it is.

      I wondered about this. I know that every cell in a female deactivates one of the X chromosomes - I wonder if this is XISTs function and now they're using it to deactivate other chromosomes.

      Also the statement
      " XIST is a gene vital to embryonic development. It plays a major role in gender determination by silencing the second X chromosome thereby turning the foetus male (if it doesn’t turn on, the second X chromosome remains active and the baby will be female)."

      I do not believe is correct, turning off an X will not instantly make the foetus male, the foetus gender is determined by if the sperm has an X or a Y.

      Mammals regardless of gender only have one active X (as samsam also said).

      Last edited 20/07/13 10:31 am

        Hi Tim.

        It seems they are intending to say that the X chromosome in Males is masked/deactivated to allow the Y chromosome to develop male characteristics. So claiming that they can selectively mask one C21.
        Agree, poorly written in parts.

          As far as i understand it, males have an active X and Y, since only very few genes in the X are for sex determination and the X chromosome has a lot more genes than the Y a few thousand vs a few dozen. So to futher speculate based on that, XIST doesnt operate in males, if the X was turned off in males they would not be a viable human.

            Thanks TIm.

            So the sensational header is probably just that.

            I think lots of articles such as these use evolutionary theory wrongly, claiming that all Foetuses are female in the beginning (sure they have common initial similarities, as all are human), while as you have stated, the presence of a Y chromosome is what makes a foetus male, not the absence of an X. Neither have anything to do with Trisomy 21.

            ps, I did write, "It seems they are intending", I personally don't necessarily agree, as I'm not fully familiar with the functions of XIST.


              I cant attest if the header to too sensational, i didnt even realise it was the sperm that decided gender till earlier this year when researching muscular dystrophy (which my uncle had) to be sure there was no chance i could pass it on, so my biology credentials are no where near good enough to fully comprehend the data behind it.

              I think that technically they start out as female, then the Y kicks in later on in development to make it male.

              Sorry i didn't mean for it to come out as if i was otherwise, i merely meant that if thats what they were intending (which i agree is possible they might have been) afaict they are still wrong :)

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