2020
Integration of CRISPR-engineering and hiPSC-based models of psychiatric genomics
Matos MR, Ho SM, Schrode N, Brennand KJ. Integration of CRISPR-engineering and hiPSC-based models of psychiatric genomics. Molecular And Cellular Neuroscience 2020, 107: 103532. PMID: 32712198, PMCID: PMC7484226, DOI: 10.1016/j.mcn.2020.103532.Peer-Reviewed Original ResearchConceptsPenetrant rare variantsDisease-associated variantsNeuronal cell typesPluripotent stem cellsGenomic engineeringFunctional characterizationComplex geneticsCRISPR engineeringCRISPR technologyIsogenic comparisonsPsychiatric genomicsCell typesGenetic variantsStem cellsIndividual variantsCommon variantsPolygenic disorderRare variantsVariantsComplex interplayGenomicsGenetic riskPleiotropyCRISPRGeneticsModeling the complex genetic architectures of brain disease
Fernando MB, Ahfeldt T, Brennand KJ. Modeling the complex genetic architectures of brain disease. Nature Genetics 2020, 52: 363-369. PMID: 32203467, PMCID: PMC7909729, DOI: 10.1038/s41588-020-0596-3.Peer-Reviewed Original ResearchConceptsGenetic architectureComplex genetic architectureFunctional validation studiesRelevant disease biologyIntersection of genomicsComplex genetic diseasesCombination of genesPluripotent stem cellsGene perturbationsIsogenic comparisonsMolecular mechanismsPhenotypic drug discoveryCell typesGenetic diseasesFunctional consequencesGenetic backgroundRisk variantsStem cellsCRISPRDisease biologyDrug discoveryRare variantsConfer riskGenetic diagnosisVariants
2015
Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms
Flaherty E, Brennand K. Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms. Brain Research 2015, 1655: 283-293. PMID: 26581337, PMCID: PMC4865445, DOI: 10.1016/j.brainres.2015.11.009.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCopy number variationsIsogenic hiPSC linesRare variantsFull genetic architectureGenome editing technologyPluripotent stem cellsStrong heritable componentPatient-derived humanGenetic architectureEditing technologyHeritable componentBehavioral defectsNumber variationsNew therapeutic targetsHiPSC linesGenetic backgroundStem cellsCommon variantsFunctional contributionDisease mechanismsSingle variantMouse modelHigh penetranceHiPSCsTherapeutic target