Down’s syndrome is caused by the presence of a third copy of Chromosome 21 in the human karyotype, leading to an over-expression of chromosome bands 21q22.1-q22.3, causing a host of developmental problems including mental retardation, stunted physical growth, and congenital heart disease. The best hope for those affected with the condition to lead normal, productive lives had always been proper care and education during their formative years. Now, it looks as though there may be a way to attack the disorder at its roots.
[Jeanne Lawrence, a cell biologist at the University of Massachusetts Medical School in Worcester] and her team devised an approach to mimic the natural process that silences one of the two X chromosomes carried by all female mammals. Both chromosomes contain a gene called XIST (the X-inactivation gene), which, when activated, produces an RNA molecule that coats the surface of a chromosome like a blanket, blocking other genes from being expressed. In female mammals, one copy of the XIST gene is activated — silencing the X chromosome on which it resides.
Biologists help me out … why is there only one X chromosome active in women? I thought the reason for the prevalence of genetic disorders in men (color blindness and those like it) was because we didn’t have another X to use as a “backup” as it were.
Ah. Wikipedia to the rescue. Apparently it occurs on a cellular level, not on a systemic level, making it equally probable that either one will be turned on in a given cell. They provide the example of the Calico Cat, which is too neat to ignore here. Since the X chromosome is responsible for fur color, random activation of either one in the epithelial cells is what’s responsible for the mottled pattern of orange and black. It also explains why Calicos must be female. The more you know!
Lawrence’s team spliced the XIST gene into one of the three copies of chromosome 21 in cells from a person with Down’s syndrome. The team also inserted a genetic ‘switch’ that allowed them to turn on XIST by dosing the cells with the antibiotic doxycycline. Doing so dampened expression of individual genes along chromosome 21 that are thought to contribute to the pervasive developmental problems that comprise Down’s syndrome.
It’s not perfect; it may not be completely effective in the sense that the entire chromosome gets shut down. However, it’s a promising start to eventually responding to the discovery of Down’s in utero with genetic treatment to eliminate the disorder altogether instead of formulating a care plan to manage it over the course of a lifetime.