Supplement to TR01 Human cortical development and neural plasticity altered by trisomy 21

ABSTRACT
Down syndrome (DS, trisomy 21, T21), a complex multigene disorder and the most common genetic cause of
intellectual disability. However, surprisingly little is known about the underlying mechanisms that lead to cognitive
impairment in DS. Reduced neurogenesis and synaptogenesis have been implicated as features of DS
development. Yet, what and how specific neurons and synaptic contacts are affected at which period of
development and what molecular pathways underlie these defects that lead to intellectual disability remain
unclear.
This supplement application requests funding to expand the goals of the parent award to carry out bulk whole
transcriptomics to identify diverse types of RNA species that cannot be captured using the single cell approaches
in the parent award. These results will complement the single cell results generated from the parent award and
potentially identify new gene regulatory mechanisms in DS brain development. The supplement proposal is
relevant to Component 1 of the NIH INCLUDE project: Targeted high risk - high reward basic science studies in
areas highly relevant to Down syndrome. Data generated from this award will be shared as a resource through
the INCLUDE Data Coordinating Center (DCC) to maximize and accelerated research in Down syndrome.

Grant Number: 3R01HD106197-03S1
NIH Institute/Center: NIH
Principal Investigator: ANITA BHATTACHARYYA