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dc.contributor.authorCasillas-Espinosa, PM
dc.contributor.authorPowell, KL
dc.contributor.authorZhu, M
dc.contributor.authorCampbell, CR
dc.contributor.authorMaia, JM
dc.contributor.authorRen, Z
dc.contributor.authorJones, NC
dc.contributor.authorO'Brien, TJ
dc.contributor.authorPetrovski, S
dc.date.accessioned2020-12-21T01:30:02Z
dc.date.available2020-12-21T01:30:02Z
dc.date.issued2017-07-14
dc.identifierpii: PONE-D-16-48652
dc.identifier.citationCasillas-Espinosa, P. M., Powell, K. L., Zhu, M., Campbell, C. R., Maia, J. M., Ren, Z., Jones, N. C., O'Brien, T. J. & Petrovski, S. (2017). Evaluating whole genome sequence data from the Genetic Absence Epilepsy Rat from Strasbourg and its related non-epileptic strain. PLOS ONE, 12 (7), https://doi.org/10.1371/journal.pone.0179924.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/256537
dc.description.abstractOBJECTIVE: The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbreed Wistar rat strain widely used as a model of genetic generalised epilepsy with absence seizures. As in humans, the genetic architecture that results in genetic generalized epilepsy in GAERS is poorly understood. Here we present the strain-specific variants found among the epileptic GAERS and their related Non-Epileptic Control (NEC) strain. The GAERS and NEC represent a powerful opportunity to identify neurobiological factors that are associated with the genetic generalised epilepsy phenotype. METHODS: We performed whole genome sequencing on adult epileptic GAERS and adult NEC rats, a strain derived from the same original Wistar colony. We also generated whole genome sequencing on four double-crossed (GAERS with NEC) F2 selected for high-seizing (n = 2) and non-seizing (n = 2) phenotypes. RESULTS: Specific to the GAERS genome, we identified 1.12 million single nucleotide variants, 296.5K short insertion-deletions, and 354 putative copy number variants that result in complete or partial loss/duplication of 41 genes. Of the GAERS-specific variants that met high quality criteria, 25 are annotated as stop codon gain/loss, 56 as putative essential splice sites, and 56 indels are predicted to result in a frameshift. Subsequent screening against the two F2 progeny sequenced for having the highest and two F2 progeny for having the lowest seizure burden identified only the selected Cacna1h GAERS-private protein-coding variant as exclusively co-segregating with the two high-seizing F2 rats. SIGNIFICANCE: This study highlights an approach for using whole genome sequencing to narrow down to a manageable candidate list of genetic variants in a complex genetic epilepsy animal model, and suggests utility of this sequencing design to investigate other spontaneously occurring animal models of human disease.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleEvaluating whole genome sequence data from the Genetic Absence Epilepsy Rat from Strasbourg and its related non-epileptic strain
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0179924
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.departmentMedicine (RMH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePLoS One
melbourne.source.volume12
melbourne.source.issue7
melbourne.identifier.nhmrc1126877
dc.rights.licenseCC BY
melbourne.elementsid1223401
melbourne.contributor.authorO'Brien, Terence
melbourne.contributor.authorJones, Nigel
melbourne.contributor.authorCasillas Espinosa, Pablo
melbourne.contributor.authorPowell, Kim
melbourne.contributor.authorPetrovski, Slave
melbourne.contributor.authorCasillas Espinosa, Pablo Miguel
dc.identifier.eissn1932-6203
melbourne.identifier.fundernameidNHMRC, 1126877
melbourne.accessrightsOpen Access


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