We show here, in comparisons between Ts65Dn/Erg+/+/+ mice, in which a ~104-gene interval syntenic to HSA21 is present in trisomy, and their Ts65Dn/Erg+/+/Mld2 counterparts, in which the Erg gene within this interval is specifically reduced to functional disomy, that trisomy of Erg is specifically required for the characteristic perturbations in specific hematopoietic progenitor cell populations in the Ts(1716)65Dn DS model. This evidence concerns the gene ERG and Dravet syndrome.