2021
Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection
Dobrindt K, Hoagland DA, Seah C, Kassim B, O'Shea CP, Murphy A, Iskhakova M, Fernando MB, Powell SK, Deans PJM, Javidfar B, Peter C, Møller R, Uhl SA, Garcia MF, Kimura M, Iwasawa K, Crary JF, Kotton DN, Takebe T, Huckins LM, tenOever BR, Akbarian S, Brennand KJ. Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection. Stem Cell Reports 2021, 16: 505-518. PMID: 33636110, PMCID: PMC7881728, DOI: 10.1016/j.stemcr.2021.02.010.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdolescentAdultAnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCOVID-19FemaleFurinGenetic Predisposition to DiseaseHost-Pathogen InteractionsHumansInduced Pluripotent Stem CellsMaleNeuronsPeptide HydrolasesPolymorphism, Single NucleotideSARS-CoV-2Vero CellsConceptsSARS-CoV-2Clinical complicationsSARS-CoV-2 infectionCommon genetic variationHigh-risk individualsHost genetic variantsSignificant interindividual variabilityNeuron infectionUnderlying comorbiditiesViral loadHealthy individualsViral infectionClinical heterogeneityVitro SusceptibilityEtiologic agentHost responseInterindividual variabilityDiscovery of drugsInfectionHost geneticsHuman induced pluripotent stem cellsSingle nucleotide polymorphismsAntibody repertoireMore diseasesComplications
2020
Massively parallel techniques for cataloguing the regulome of the human brain
Townsley KG, Brennand KJ, Huckins LM. Massively parallel techniques for cataloguing the regulome of the human brain. Nature Neuroscience 2020, 23: 1509-1521. PMID: 33199899, PMCID: PMC8018778, DOI: 10.1038/s41593-020-00740-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsBrainClustered Regularly Interspaced Short Palindromic RepeatsGene Expression RegulationGeneticsHigh-Throughput Screening AssaysHumansInduced Pluripotent Stem CellsRegulatory Elements, TranscriptionalConceptsRegulatory elementsTarget genesParallel reporter assaysPutative regulatory elementsNon-coding regionsDisease-associated lociSpecific expression patternsCandidate risk lociPluripotent stem cellsHigh-throughput assaysRelevant molecular pathwaysTranscriptional responseRegulatory architectureRisk lociExpression patternsReporter assaysComplex brain disordersMolecular pathwaysRegulomeStem cellsRisk architectureGenetic riskGenesLociGenetic diagnosisIntegration 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 ResearchMeSH KeywordsAnimalsBrain DiseasesClustered Regularly Interspaced Short Palindromic RepeatsGene EditingHumansInduced Pluripotent Stem CellsMental DisordersNeuronsConceptsPenetrant 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 ResearchMeSH KeywordsAnimalsBrain DiseasesClustered Regularly Interspaced Short Palindromic RepeatsGenomeHumansInduced Pluripotent Stem CellsPrecision MedicineConceptsGenetic 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 diagnosisVariantsIntegrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems
Rehbach K, Fernando MB, Brennand KJ. Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems. Journal Of Neuroscience 2020, 40: 1176-1185. PMID: 32024766, PMCID: PMC7002154, DOI: 10.1523/jneurosci.0518-19.2019.Peer-Reviewed Original ResearchMeSH KeywordsClustered Regularly Interspaced Short Palindromic RepeatsGene EditingHumansInduced Pluripotent Stem CellsModels, GeneticConceptsHuman induced pluripotent stem cellsMajor brain cell typesDual Perspectives CompanionBrain cell typesNeuronal maturityPsychiatric disordersHuman neuronsDisease riskStudy designBrain organoidsIntradonor variabilityDisease modelsHuman neurodevelopmentInduced pluripotent stem cellsNeural differentiationDiseaseStem cellsCell typesPluripotent stem cellsHuman diseasesEfficient neural differentiationInduction strategyPatient-specific cellsDisease modelingCells
2019
CRISPR-based functional evaluation of schizophrenia risk variants
Rajarajan P, Flaherty E, Akbarian S, Brennand KJ. CRISPR-based functional evaluation of schizophrenia risk variants. Schizophrenia Research 2019, 217: 26-36. PMID: 31277978, PMCID: PMC6939156, DOI: 10.1016/j.schres.2019.06.017.Peer-Reviewed Original ResearchMeSH KeywordsBrainClustered Regularly Interspaced Short Palindromic RepeatsGenomeHumansInduced Pluripotent Stem CellsSchizophreniaConceptsSchizophrenia-associated variantsPluripotent stem cellsCRISPR genome engineeringSchizophrenia risk variantsCellular functionsGenome engineeringGenomic studiesSchizophrenia lociList of variantsGene expressionPatient-specific humanGenotype dataRisk variantsStem cellsFunctional impactCommon variantsCRISPRPost-mortem brain tissueRecent findingsVariantsNeuropsychiatric diseasesPoint of convergenceGenetic riskLociSpecific effects