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Down syndrome (DS) arises from an extra copy of an entire human chromosome, 21 (Hsa21) (trisomy 21), resulting in a wide constellation of phenotypes; in addition to learning and memory deficits, there are greatly increased risks for congenital heart defects, early-onset Alzheimer’s disease and leukemia. DS is a common disorder, with a prevalence of around 1 in 750 births, a frequency that is not diminishing despite the availability of pre-natal diagnosis. It is the leading genetic cause of cognitive impairment. DS is a disorder of gene dosage for one or more of the ~300 genes on Hsa21, affecting many different systems, with variable severity and expressivity. Research into DS has recently come of age with the development of sophisticated cell and animal models, novel biological findings and clinical trials of therapeutics. Despite this growing research into DS and the number of people affected by it, there is no regular scientific meeting devoted to the syndrome. This interdisciplinary Keystone Symposia meeting on DS brings together experts from disparate research fields (genetics, development, stem cell biology and neuroscience), all focused on the effects of trisomy 21. The goals of the meeting are to: 1) Provide an interdisciplinary meeting covering all aspects of DS research from genetics and cell biology using animal models to human studies and therapy; 2) Encourage interactions and new interdisciplinary collaborations in DS research; 3) Set standards for animal models, cellular assays and clinical phenotyping relevant to DS; 4) Provide a forum in which academia and industry can interact in order to promote translation of research toward therapy.