PUBLICATION
Multi-omic analyses identify molecular targets of Chd7 that contribute to CHARGE syndrome model phenotypes
- Authors
- Hancock, M.B., Ruby, D.R., Bieler, R.A., Cole, D.C., Marsden, K.C.
- ID
- ZDB-PUB-260210-15
- Date
- 2026
- Source
- Disease models & mechanisms : (Journal)
- Registered Authors
- Marsden, Kurt
- Keywords
- Behavior, CHARGE syndrome, CHD7, Developmental disorder, Proteomics, Transcriptomics
- MeSH Terms
- none
- PubMed
- 41664627 Full text @ Dis. Model. Mech.
Citation
Hancock, M.B., Ruby, D.R., Bieler, R.A., Cole, D.C., Marsden, K.C. (2026) Multi-omic analyses identify molecular targets of Chd7 that contribute to CHARGE syndrome model phenotypes. Disease models & mechanisms. :.
Abstract
CHARGE syndrome is a developmental disorder that affects 1 in 10,000 births, and patients exhibit both physical and behavioral characteristics. De novo mutations in CHD7 (chromodomain helicase DNA binding protein 7) cause 67% of CHARGE syndrome cases. CHD7 is a DNA-binding chromatin remodeler with thousands of predicted binding sites in the genome, making it challenging to define molecular pathways linking loss of CHD7 to CHARGE phenotypes. To address this problem, here we used a previously characterized zebrafish CHARGE model to generate transcriptomic and proteomic datasets from larval zebrafish head tissue at two developmental time points. By integrating these datasets with differential expression, pathway, and upstream regulator analyses, we identified multiple consistently dysregulated pathways and defined a set of candidate genes that link loss of chd7 with disease-related phenotypes. Finally, to functionally validate the roles of these genes, CRISPR/Cas9-mediated knockdown of capgb, nefla, or rdh5 phenocopies behavioral defects seen in chd7 mutants. Our data provide a resource for further investigation of molecular mediators of CHD7 and a template to reveal functionally relevant therapeutic targets to alleviate specific aspects of CHARGE syndrome.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping