Featured Publications
Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk
Rajarajan P, Borrman T, Liao W, Schrode N, Flaherty E, Casiño C, Powell S, Yashaswini C, LaMarca EA, Kassim B, Javidfar B, Espeso-Gil S, Li A, Won H, Geschwind DH, Ho SM, MacDonald M, Hoffman GE, Roussos P, Zhang B, Hahn CG, Weng Z, Brennand KJ, Akbarian S. Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk. Science 2018, 362 PMID: 30545851, PMCID: PMC6408958, DOI: 10.1126/science.aat4311.Peer-Reviewed Original ResearchMeSH KeywordsBrainCells, CulturedChromatinChromatin Assembly and DisassemblyChromosomes, HumanConnectomeEpigenesis, GeneticGene Expression Regulation, DevelopmentalGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHumansMaleNeural Stem CellsNeurogenesisNeurogliaNeuronsNucleic Acid ConformationProtein Interaction MapsProteomicsRiskSchizophreniaTranscription, GeneticTranscriptomeConceptsCoordinated transcriptional regulationThree-dimensional genomeSpatial genome organizationChromosomal contact mapsNeural progenitor cellsSchizophrenia risk variantsGenome organizationChromatin remodelingChromosomal conformationTranscriptional regulationProteomic interactionsDevelopmental remodelingHeritable riskGlial differentiationRisk variantsContact mapsProgenitor cellsVariant sequencesGenesConformation changeNeuronal connectivitySchizophrenia riskSequenceNeuropsychiatric diseasesDistal targets
2019
Spatial genome exploration in the context of cognitive and neurological disease
Rajarajan P, Borrman T, Liao W, Espeso-Gil S, Chandrasekaran S, Jiang Y, Weng Z, Brennand KJ, Akbarian S. Spatial genome exploration in the context of cognitive and neurological disease. Current Opinion In Neurobiology 2019, 59: 112-119. PMID: 31255842, PMCID: PMC6889018, DOI: 10.1016/j.conb.2019.05.007.Peer-Reviewed Original ResearchConceptsGenome explorationSpecific gene expression programsImportant regulatory layerTopological chromatin domainsGene expression programsChromosomal contact mapsChromatin domainsGenome organizationExpression programsRegulatory layerTranscriptional regulationChromosomal contactsWidespread remodelingTranscriptomic analysisRepeat sequencesUnexpected linkNeuronal lineageNeural differentiationNon-contiguous sequencesContact mapsAbnormal expansionNeurodegenerative diseasesNew insightsSequenceMouse brain
2016
Spatial genome organization and cognition
Rajarajan P, Gil S, Brennand K, Akbarian S. Spatial genome organization and cognition. Nature Reviews Neuroscience 2016, 17: 681-691. PMID: 27708356, PMCID: PMC5503467, DOI: 10.1038/nrn.2016.124.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPromoter-enhancer interactionsRegulatory sequencesGene transcription start siteSpatial genome organizationNon-coding DNACis-regulatory sequencesHundreds of kilobasesTranscription start siteCRISPR-Cas systemsChromosomal loopingGenome organizationTranscriptional activatorChromosomal conformationCohesin complexGenetic risk architectureTranscriptional regulationStart siteCandidate genesGene expressionStructural variantsDecoy modelsNeurodevelopmental diseasesCrucial layerEditing techniquesProgenitor cells
2014
A Role for Noncoding Variation in Schizophrenia
Roussos P, Mitchell A, Voloudakis G, Fullard J, Pothula V, Tsang J, Stahl E, Georgakopoulos A, Ruderfer D, Charney A, Okada Y, Siminovitch K, Worthington J, Padyukov L, Klareskog L, Gregersen P, Plenge R, Raychaudhuri S, Fromer M, Purcell S, Brennand K, Robakis N, Schadt E, Akbarian S, Sklar P. A Role for Noncoding Variation in Schizophrenia. Cell Reports 2014, 9: 1417-1429. PMID: 25453756, PMCID: PMC4255904, DOI: 10.1016/j.celrep.2014.10.015.Peer-Reviewed Original ResearchMeSH KeywordsArthritis, RheumatoidCalcium Channels, L-TypeDatabases, GeneticDNA, IntergenicEnhancer Elements, GeneticGene Expression RegulationGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMolecular Sequence AnnotationOrgan SpecificityPolymorphism, Single NucleotidePromoter Regions, GeneticProtein BindingRisk FactorsSchizophreniaConceptsExpression quantitative trait lociGenome-wide significant lociCommon variant lociQuantitative trait lociPluripotent stem cell-derived neuronsDistal regulatory elementsStem cell-derived neuronsPotential physical interactionsCell-derived neuronsRegulatory element sequencesPotential functional roleGenome architectureChromosomal loopingTranscriptional regulationFunctional annotationTrait lociSignificant lociNoncoding SNPsRegulatory elementsNoncoding variationsRisk lociVariant lociUnknown functionFunctional linkElement sequences