2023
Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene
Fernandez T, Williams Z, Kline T, Rajendran S, Augustine F, Wright N, Sullivan C, Olfson E, Abdallah S, Liu W, Hoffman E, Gupta A, Singer H. Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene. PLOS ONE 2023, 18: e0291978. PMID: 37788244, PMCID: PMC10547198, DOI: 10.1371/journal.pone.0291978.Peer-Reviewed Original ResearchConceptsRisk genesDe novo damaging variantsGene expression patternsWhole-exome DNA sequencingMid-fetal developmentAdditional risk genesHigh-confidence risk genesParent-child triosGene OntologyCell signalingExpression patternsCalcium ion transportFunctional convergenceCell cycleDamaging variantsGenesDNA sequencingDe novoASD probandsGenetic etiologyBiological mechanismsSequencingDNANetwork analysisIon transportHigh-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways
Mendes H, Neelakantan U, Liu Y, Fitzpatrick S, Chen T, Wu W, Pruitt A, Jin D, Jamadagni P, Carlson M, Lacadie C, Enriquez K, Li N, Zhao D, Ijaz S, Sakai C, Szi C, Rooney B, Ghosh M, Nwabudike I, Gorodezky A, Chowdhury S, Zaheer M, McLaughlin S, Fernandez J, Wu J, Eilbott J, Vander Wyk B, Rihel J, Papademetris X, Wang Z, Hoffman E. High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways. Cell Reports 2023, 42: 112243. PMID: 36933215, PMCID: PMC10277173, DOI: 10.1016/j.celrep.2023.112243.Peer-Reviewed Original ResearchConceptsGene lossFunctional analysisHigh-throughput functional analysisZebrafish mutantsGene discoverySelect mutantsASD genesAutism genesKey pathwaysASD biologyBrain size differencesMutantsGenesSize differencesPathwayGlobal increaseRelevant mechanismsBiologyCentral challengeNeuroimmune dysfunctionRegionFunctionDiscoveryAutism spectrum disorder
2021
Signaling Pathways and Sex Differential Processes in Autism Spectrum Disorder
Enriquez KD, Gupta AR, Hoffman EJ. Signaling Pathways and Sex Differential Processes in Autism Spectrum Disorder. Frontiers In Psychiatry 2021, 12: 716673. PMID: 34690830, PMCID: PMC8531220, DOI: 10.3389/fpsyt.2021.716673.Peer-Reviewed Original ResearchASD genetic studiesBiological pathwaysGenetic studiesRisk gene discoveryCellular pathways downstreamASD risk genesWhole-exome sequencing studiesCommon biological pathwaysGene discoveryPathways downstreamGene expressionSequencing studiesRisk genesMale biasPathwayGenesNeuronal communicationCommon pathwayPotential roleFemale protective effectNeurodevelopmental disordersRecent analysisTranscriptomicsGenomicsRecent investigationsA simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes
Kroll F, Powell GT, Ghosh M, Gestri G, Antinucci P, Hearn TJ, Tunbak H, Lim S, Dennis HW, Fernandez JM, Whitmore D, Dreosti E, Wilson SW, Hoffman EJ, Rihel J. A simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes. ELife 2021, 10: e59683. PMID: 33416493, PMCID: PMC7793621, DOI: 10.7554/elife.59683.Peer-Reviewed Original ResearchConceptsKnockout methodComplex mutant phenotypesLarge genetic screenRapid genetic screeningGenetic screenMutant phenotypeEffective CRISPRBiallelic knockoutMolecular rhythmsHuman genesInjected embryosCircadian clockLarval zebrafishBehavioral phenotypesMultiple genesComplex phenotypesCurrent CRISPRTriple knockoutAttractive modelGenesGenetic contributionZebrafishPhenotypeKnockoutCRISPR
2020
Chapter 26 Modeling autism spectrum disorders in zebrafish
Dreosti E, Hoffman E, Rihel J. Chapter 26 Modeling autism spectrum disorders in zebrafish. 2020, 451-480. DOI: 10.1016/b978-0-12-817528-6.00026-7.ChaptersZebrafish modelGenetics of ASDGenome-wide association studiesHundreds of genesNervous system formComplex behavioral repertoireHuman neurodevelopmental disordersWhole-genome sequencingExcellent systemGenetic informationGenome sequencingAssociation studiesGenerate mutationsZebrafishUnique human traitsHuman traitsHuman biologyNeurodevelopmental disordersASD biologyGenetic alterationsRapid discoveryGenesBiologyBehavioral repertoireNeuronal processes
2018
Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future
Sakai C, Ijaz S, Hoffman EJ. Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future. Frontiers In Molecular Neuroscience 2018, 11: 294. PMID: 30210288, PMCID: PMC6123572, DOI: 10.3389/fnmol.2018.00294.Peer-Reviewed Original ResearchGene functionZebrafish modelCRISPR/Cas9 geneSmall-molecule suppressorTransparent embryosZebrafish systemHigh-throughput pharmacological screensNeurodevelopmental disordersGenetic manipulationCas9 geneBehavioral phenotypesLarge progenyFunctional analysisLarval stagesPharmacological screensZebrafishRisk genesGenesModel systemExternal developmentPhenotypeCircuit-level mechanismsBasic mechanismsNeural circuitsNervous system
2013
Coexpression Networks Implicate Human Midfetal Deep Cortical Projection Neurons in the Pathogenesis of Autism
Willsey AJ, Sanders SJ, Li M, Dong S, Tebbenkamp AT, Muhle RA, Reilly SK, Lin L, Fertuzinhos S, Miller JA, Murtha MT, Bichsel C, Niu W, Cotney J, Ercan-Sencicek AG, Gockley J, Gupta AR, Han W, He X, Hoffman EJ, Klei L, Lei J, Liu W, Liu L, Lu C, Xu X, Zhu Y, Mane SM, Lein ES, Wei L, Noonan JP, Roeder K, Devlin B, Sestan N, State MW. Coexpression Networks Implicate Human Midfetal Deep Cortical Projection Neurons in the Pathogenesis of Autism. Cell 2013, 155: 997-1007. PMID: 24267886, PMCID: PMC3995413, DOI: 10.1016/j.cell.2013.10.020.Peer-Reviewed Original ResearchConceptsCoexpression networkASD genesComplex developmental syndromeGenome-wide sequencingCortical projection neuronsHigh-confidence ASD genesExpression data setsPleiotropic genesSpecific genesDevelopmental processesDevelopmental syndromesSequencing studiesGenesProjection neuronsCell typesBrain regionsType mutationsCommon phenotypeASD pathophysiologyPathogenesis of autismAutism spectrum disorderMutationsHuman brain regionsUnknown etiologyRecent studies