Down syndrome trisomy 21 chromosome turned off

Breakthrough in research: Geneticists inactivate the chromosome in the laboratory

07/18/2013

Scientists from the US is an immense progress in the therapy of the so-called „down syndrome“ succeeded because they could turn off the disease causing chromosome. But until the new findings could actually be implemented within the treatment, research would still require several years of research, according to the researchers.

Disease is caused by genommutation
Like the expert team of the „University of Massachusetts Medical School“ in Worcester in the Wednesday issue of the journal „Nature“ reported, it had succeeded in the context of laboratory experiments, the additional chromosome, which the „Down syndrom“ caused by a Genommutation the entire 21 chromosome or parts of it in triplicate, which is why the disease is commonly referred to as „Trisomy 21“ referred to as. With this result, according to the research team „the essential first step towards the possible development of a 'chromosome therapy' has been overcome.“

Scientists are guided by concept from nature
In their article, researchers led by Jeanne Lawrence of the University of Massachusetts describe how they succeeded in eliminating the third copy of chromosome 21 in human cells - and that was the central idea behind the project, „to test the concept that a genetic imbalance could be corrected by an extra chromosome de facto by the manipulation of a single gene“, so the scientists in their article.

The female genome also contains a decommissioned chromosome
With this approach, the researchers followed a procedure that is already well known from nature, because the female genome is two copies of the so-called „X chromosome“ one of them will also be shut down. Therefore, there are two X chromosomes in the female cells, each with a very different degree of activity: While one takes on all the important functions in the cell metabolism, the other X chromosome is inactive - but it is prevented „sister chromosome“ not at work.

Inactivation by a single gene
For the inactivation of the X chromosome is responsible only a single gene - more precisely, the so-called „X-Inaktivierungsgen“ ("XIST"), according to the researchers in the current study has now shown that this can turn off not only the sex chromosome, but also an excess chromosome 21. Now the researchers hope that the newly won „Basic evidence points exciting ways to reexamine Down syndrome“, as the cell and developmental biologist and lead author of the study, Jeanne Lawrence, writes. However, years of research are still needed, because since the immobilization of the chromosome has hitherto only functioned in the laboratory, an application on humans is still a long way off.

Trisomy 21 occurs in very different forms
In addition, with regard to the new findings, there would be an application in the womb, in which by the method, so to speak, the Down syndrome „switched off“ This would not only be risky, but would also be a serious problem from an ethical point of view, because trisomy 21 occurs in very different ways: some children show only minor intellectual losses and basically develop „normal“, while in other cases the disease can lead to severe organ damage (especially of the heart and intestine), there is an increased risk for an early form of dementia. Precisely because of the serious damage caused by trisomy 21 in many cases, according to the US researchers „The cell and development pathology of human Down's syndrome will be better understood in order to develop successful treatments.“

Cause of trisomy 21 in most cases an unusual nuclear division
The cause of the so-called „Down's syndrome“ is in most cases in an unusual running „meiosis“ or division of the cell nucleus, in which either the homologous chromosomes in the first division of the maturation or the chromatids in the second division of the meiosis are not separated. What causes this non-separation is not yet known - but one thesis is that the influence of ionizing radiation supports this process. In addition, since the likelihood of giving birth to a child with trisomy 21 increases with age of the mothers, it also suggests that oocyte damage in general - be it from radiation or the natural aging process - could be a risk for unusual meiosis increase. (No)

Image: Gabi Schoenemann