Whole Genome Sequence Data From Captive Baboons Implicate RBFOX1 in Epileptic Seizure Risk

Area of Science:

• Genetics
• Neuroscience
• Primate Models

Background:

• Epilepsy has complex genetic underpinnings.
• Non-human primate models offer insights into human disease genetics.
• Understanding genetic epilepsy etiology is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate genetic determinants of epilepsy in a baboon pedigree.
• To assess the utility of baboons as a model for human genetic generalized epilepsy (GGE).
• To identify candidate genes and pathways associated with epilepsy in baboons.

Main Methods:

• Whole-genome sequencing data analysis using candidate gene and genome-wide approaches.
• SNP analysis targeting 19 GGE-associated human genes and genome-wide protein-altering variants.
• Association testing (SOLAR), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) network construction.

Main Results:

• Significant association of an intronic SNP in RBFOX1 with epileptic seizures in baboons (p = 5.92 × 10^-6).
• No genome-wide significant associations for protein-altering variants.
• GSEA revealed enrichment for extracellular matrix (ECM) and collagen formation genes in epilepsy-associated pathways.

Conclusions:

• RBFOX1 may play a role in baboon epilepsy, similar to its role in human epilepsy.
• Genetic variants in ECM and collagen pathways are associated with epilepsy risk in baboons.
• This study supports the baboon as a relevant model for investigating the genetic basis of human GGE.