Beyond Gene Dosage: Understanding Down Syndrome via 4D Genome Organization

Li, Wenbo


Down Syndrome is the most common human genetic disease due to chromosome aneuploidy (trisomy 21), but the molecular basis for gene deregulation in these patients remains largely enigmatic or debatable, which can be partially attributed to our lack of understanding of 3D genome organization in trisomy 21 that may conceptually go beyond the limit of “gene dosage effects”. In this proposal, we apply leading-edge 4D genome technologies to pioneer an underexplored direction that the extra copy of chromosome 21 may deregulate the entire 4D genome organization in disease cells, and impact gene expression. The results of this work will have broad implications to understand, and to therapeutically treat chromosomal aneuploidy commonly seen in many human diseases, such as cancer, congenital heart diseases and neurodevelopmental disorders.