How to correct chromosomal trisomy

Abstract

Trisomy 21 in human causes Down syndrome, a common chromosome disorder with devastating phenotypes ranging from early death in utero to intellectual disability together with an array of physical anomalies and late-onset diseases. In a recent study published in Nature, Jeanne Lawrence and her colleagues restored normal gene expression in trisomy 21 cells by silencing the extra chromosome using XIST, the non-coding RNA that normally silences one X chromosome in females; this improved growth and differentiation of neural cells, which offers hope that some deleterious effects of the trisomy could be reversed to improve this incurable disease.

Figure 1

Trisomy 21 rescue. Euploid cells can arise from a population of trisomy 21 cells by several mechanisms: spontaneous loss of chromosome 21 together with growth advantage of euploid cells (left); induced loss of chromosome 21 using a selectable marker (TKNEO) targeted to the APP gene (middle); or induced silencing of one chromosome 21 by insertion of XIST into the DYRKY1A gene (right).