Together, these observations suggest that 17 upregulated genes on HC21 may be involved in the development of DS and provide the basis for understanding this disability.
HC21 sequencing, mouse ortholog gene identification and DS mouse model generation lead to determine HC21 gene functions and the effects of protein-dosage alterations in neurodevelopmental and metabolic pathways in DS individuals.
The effects of the gene dosage imbalance on DS phenotypes are explained by two hypotheses: the "gene dosage effect" hypothesis claims that a DS critical region, containing a subset of dosage-sensitive genes, determines DS phenotypes, and the "amplified developmental instability" hypothesis holds that HC21 trisomy determines general alteration in developmental homeostasis.
Down Syndrome (DS) is caused by the presence of three copies of the whole human chromosome 21 (HC21) or of a HC21 restricted region; the phenotype is likely to have originated from the altered expression of genes in the HC21.
Novel therapeutic interventions for Down syndrome and the monogenic and polygenic disorders that map to HC21 will be designed and tried based on the knowledge of the disease pathogenesis resulting from the genomic analysis.