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Collaborative Cross Mouse Populations as a Resource for the Study of Epilepsy

Gu, B.; Shorter, J. R.; Williams, L. H.; Bell, T. A.; Hock, P.; Dalton, K. A.; PAN, Y.; Miller, D. R.; Shaw, G. D.; Cooley, B. C.; Philpot, B. D.; Pardo Manuel de Villena, F.

2019-07-15 neuroscience
10.1101/690917 bioRxiv
Show abstract

Epilepsy is a neurological disorder with complex etiologies and genetic architecture. Animal models have a critical role in understanding the pathophysiology of epilepsy. Here we studied epilepsy utilizing a genetic reference population of Collaborative Cross (CC) mice with publicly available whole genome sequences. We measured multiple epilepsy traits in 35 CC strains, and we identified novel animal models that exhibit extreme outcomes in seizure susceptibility, seizure propagation, epileptogenesis, and sudden unexpected death in epilepsy. We performed QTL mapping in an F2 population and identified seven novel and one previously identified loci associated with seizure sensitivity. We combined whole genome sequence and hippocampal gene expression to pinpoint biologically plausible candidate genes and candidate variants associated with seizure sensitivity. These resources provide a powerful toolbox for studying complex features of seizures and for identifying genes associated with particular seizure outcomes, and hence will facilitate the development of new therapeutic targets for epilepsy.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.