Award Details:
Award Type: Catalyst
Award #: C-100
Proposal Title: The Impact of Altering Genome Organization in Epilepsy Etiology
PI(s): Marcelo Nobrega (UChicago) and Gemma Carvill (NU)
Award Amount: $245,504.00
Application Cycle: Round 29 (Spring 2020)
Award Start Date: October 1, 2020
Award End Date: September 1, 2022
Abstract:
Structural variation (SV) of the genome contributes significantly to the etiology of epilepsy; and is likely underestimated due to the limitations of standard detection techniques. Genome sequencing enables the detection of smaller and more complex SVs. However, a major challenge with increased SV detection is (1) our inability to distinguish between pathogenic and benign SVs and (2) our limited understanding of causal genes and mechanisms. In this Catalyst Award we propose a novel chromatin capture technique, TAD Capture Hi-C (TADC-Hi-C) that will detect SVs that alter the 3D organization of the genome and disrupt gene expression in epilepsy. These topologically associated domains (TADs) contain genes that tend to be co-regulated and TAD boundary disruption has been linked to developmental malformations and cancers. We propose to develop and implement TADC-Hi-C to identify pathogenic epilepsy-associated SVs and dissect the pathogenic mechanisms of a recurrent SV, 16p13.11 microdeletion.