Understanding the complexity of gene dosage imbalance in Down syndrome

The overall theme is to produce novel, medically relevant knowledge that advances our understanding of gene dosage imbalance in Down syndrome (DS), with a particular interest in DS-associated leukemia. The studies proposed have innovative solutions to major challenges that have been identified in the field, and will provide a comprehensive and comparative view of genome-wide transcriptome and chromatin architecture using isogenic DS induced pluripotent stem cells that differ only by copy number of HSA21 or specific candidate genes.