It is well known that a third copy of chromosome 21 (trisomy 21) causes Down syndrome; however, the molecular processes that occur as a result are not well understood. In this landmark publication, Drs. Kelly Sullivan and Joaquin Espinosa use complementary genomics techniques and transcriptome analyses on multiple cell lines and human blood samples to show that trisomy 21 consistently activates the interferon signaling cascade across a variety of cell types. Furthermore, they show that the interferon-activated kinases JAK1 and TYK2 suppress proliferation of trisomy 21 fibroblasts. They hypothesize these findings are likely due to the fact that four of the six interferon receptors are encoded on chromosome 21, and that the aberrant interferon signaling could contribute to many of the clinical impacts of trisomy 21.
Trisomy 21 consistently activates the interferon response. Sullivan KD, Lewis HC, Hill AA, Pandey A, Jackson LP, Cabral JM, Smith KP, Liggett LA, Gomez EB, Galbraith MD, DeGregori J, Espinosa JM. Elife. 2016 Jul 29;5. PMID: 27472900.