2021
Mutations of the histone linker H1–4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4
Tremblay MW, Green MV, Goldstein BM, Aldridge AI, Rosenfeld JA, Streff H, Tan WD, Craigen W, Bekheirnia N, Al Tala S, West AE, Jiang YH. Mutations of the histone linker H1–4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4. Human Molecular Genetics 2021, 31: 1430-1442. PMID: 34788807, PMCID: PMC9271223, DOI: 10.1093/hmg/ddab321.Peer-Reviewed Original ResearchConceptsC-terminusGenome-wide transcriptome analysisRahman syndromeUnderstanding of mutationsHistone H1.4Neuronal genesTranscriptome analysisAbnormal C-terminusFunctional categoriesFunctional characterizationNeuropeptide signalingN-terminusDe novo heterozygous mutationsSupport of pathogenicitySmall insertionsFunctional consequencesNovo heterozygous mutationRat hippocampal neuronsFrameshift mutationMutationsH1.4Rare genetic disorderSevere intellectual disabilityGenesClinical features
2020
High genetic burden in 163 Chinese children with status epilepticus
Wang T, Wang J, Ma Y, Zhou H, Ding D, Li C, Du X, Jiang YH, Wang Y, Long S, Li S, Lu G, Chen W, Zhou Y, Zhou S, Wang Y. High genetic burden in 163 Chinese children with status epilepticus. Seizure 2020, 84: 40-46. PMID: 33278787, DOI: 10.1016/j.seizure.2020.10.032.Peer-Reviewed Original ResearchConceptsNon-genetic aetiologyGenetic etiologyMonogenic mutationsNumber variation analysisMolecular dataSingle geneNext-generation sequencingGene mutationsPathogenic genetic variantsUncertain significance variantsCausative variantsGenetic variantsMutationsDe novoGenetic burdenStatus epilepticusGenetic testing methodsHigher genetic burdenGenesMedical GeneticsMonogenic variantsVariation analysisVariantsTSC2Genetics
2019
Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly
Yang R, Walder-Christensen KK, Lalani S, Yan H, García-Prieto ID, Álvarez S, Fernández-Jaén A, Speltz L, Jiang YH, Bennett V. Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 19717-19726. PMID: 31451636, PMCID: PMC6765234, DOI: 10.1073/pnas.1909989116.Peer-Reviewed Original ResearchConceptsΒ4-spectrinAxon initial segmentC-terminal domainNormal neural developmentPrevents recruitmentGiant ankyrinNeural developmentConformational changesMissense mutationsMutationsPhosphorylationSegment assemblyRecruitmentMouse brainClose appositionCore mechanismDomainAssemblyAnkyrinClosed configurationIntermediate stageInitial segmentSitesProximal axonsANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity
Yang R, Walder-Christensen KK, Kim N, Wu D, Lorenzo DN, Badea A, Jiang YH, Yin HH, Wetsel WC, Bennett V. ANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 15262-15271. PMID: 31285321, PMCID: PMC6660793, DOI: 10.1073/pnas.1904348116.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsAnkyrinsAutism Spectrum DisorderBehavior, AnimalCell MembraneConnectomeDisease Models, AnimalExecutive FunctionGene ExpressionGene Knock-In TechniquesHumansMaleMiceMice, TransgenicMicrotubulesMutationNeural Cell Adhesion Molecule L1Neuronal OutgrowthNeuronsPrimary Cell CultureSocial BehaviorSynapsesDNA Methylation and Susceptibility to Autism Spectrum Disorder
Tremblay MW, Jiang YH. DNA Methylation and Susceptibility to Autism Spectrum Disorder. Annual Review Of Medicine 2019, 70: 151-166. PMID: 30691368, PMCID: PMC6597259, DOI: 10.1146/annurev-med-120417-091431.Peer-Reviewed Original ResearchConceptsDNA methylationAbnormal DNA methylationDNA methylation reprogrammingGenome-wide changesMethylation-dependent regulationMethylation reprogrammingEpigenetic machineryNext-generation sequencingEmbryonic developmentMolecular basisDNA modificationsMethylationASD etiologyGenetic mutationsAttractive hypothesisRecent advancesReprogrammingEpimutationsTranscriptionASD casesMultiple levelsMachinerySequencingTechnical advancesMutations
2018
Epigenetics and autism spectrum disorder: A report of an autism case with mutation in H1 linker histone HIST1H1E and literature review
Duffney LJ, Valdez P, Tremblay MW, Cao X, Montgomery S, McConkie‐Rosell A, Jiang Y. Epigenetics and autism spectrum disorder: A report of an autism case with mutation in H1 linker histone HIST1H1E and literature review. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2018, 177: 426-433. PMID: 29704315, PMCID: PMC5980735, DOI: 10.1002/ajmg.b.32631.Peer-Reviewed Original ResearchConceptsLinker proteinH1 linker histonesLinker histone proteinFamily member EChromatin organizationEpigenetic machineryHistone proteinsEpigenetic regulationLinker histonesNucleosome packagingLoss of functionDeleterious mutationsCandidate genesExpression studiesHistone writersWhole-exome sequencingHuman diseasesGenesProteinMutationsProtein expressionExome sequencingGenetic mutationsMember EHIST1H1ESystematic reconstruction of autism biology from massive genetic mutation profiles
Luo W, Zhang C, Jiang YH, Brouwer CR. Systematic reconstruction of autism biology from massive genetic mutation profiles. Science Advances 2018, 4: e1701799. PMID: 29651456, PMCID: PMC5895441, DOI: 10.1126/sciadv.1701799.Peer-Reviewed Original ResearchConceptsComplex genetic diseasesWhole-exome studiesHundreds of variantsGene functionNovel genesSubpathway levelGene groupsSame geneCanonical pathwaysPathway levelAutism-related mutationsSecond messenger systemsGenesGenetic diseasesASD biologyCAMP second messenger systemBiologyGenetic associationMutationsMultiple independent analysesMost variantsPathwayVariant levelsSynaptic functionGenetic mutation profiles
2017
Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain
Hulbert SW, Jiang YH. Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain. Neuroscience Bulletin 2017, 33: 205-218. PMID: 28271437, PMCID: PMC5360850, DOI: 10.1007/s12264-017-0112-7.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderDifferent neurotransmitter systemsCell typesNeurotransmitter systemsInhibitory neuronsAdult miceTransgenic miceBrain regionsCre linesDevelopmental time periodCre-loxPCertain cell typesMiceCore ASD symptomsDisordersMolecular underpinningsTime periodSpectrum disorderASD symptomsGene expressionMutations
2015
Quinidine in the treatment of KCNT1‐positive epilepsies
Mikati MA, Jiang YH, Carboni M, Shashi V, Petrovski S, Spillmann R, Milligan CJ, Li M, Grefe A, McConkie A, Berkovic S, Scheffer I, Mullen S, Bonner M, Petrou S, Goldstein D. Quinidine in the treatment of KCNT1‐positive epilepsies. Annals Of Neurology 2015, 78: 995-999. PMID: 26369628, PMCID: PMC4811613, DOI: 10.1002/ana.24520.Peer-Reviewed Original ResearchConceptsEpilepsy of infancySecondary generalized seizuresDrug-resistant epilepsySeizure frequencyGeneralized seizuresFocal seizuresKCNT1 mutationsSeizure evaluationSeizure diariesTargeted drugsTherapeutic benefitDevelopmental regressionEpilepsyGain of functionQuinidineEarly childhoodSeizuresPatientsMutationsDe novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features
Tanaka AJ, Cho MT, Retterer K, Jones JR, Nowak C, Douglas J, Jiang YH, McConkie-Rosell A, Schaefer GB, Kaylor J, Rahman OA, Telegrafi A, Friedman B, Douglas G, Monaghan KG, Chung WK. De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features. Molecular Case Studies 2015, 2: a000661. PMID: 27148580, PMCID: PMC4849844, DOI: 10.1101/mcs.a000661.Peer-Reviewed Original ResearchDysmorphic facial featuresZinc finger proteinGlobal developmental delayDevelopmental delayIntellectual disabilityFinger proteinSignificant global developmental delayMicrotubule attachmentChromosome alignmentCell divisionDe novo mutationsDe novo pathogenic variantsNovo pathogenic variantsCHAMP1Phosphoprotein 1De novoNovo mutationsUnrelated individualsFunction variantsPathogenic variantsBrain developmentMutations
2013
Deficiency of Asparagine Synthetase Causes Congenital Microcephaly and a Progressive Form of Encephalopathy
Ruzzo EK, Capo-Chichi JM, Ben-Zeev B, Chitayat D, Mao H, Pappas AL, Hitomi Y, Lu YF, Yao X, Hamdan FF, Pelak K, Reznik-Wolf H, Bar-Joseph I, Oz-Levi D, Lev D, Lerman-Sagie T, Leshinsky-Silver E, Anikster Y, Ben-Asher E, Olender T, Colleaux L, Décarie JC, Blaser S, Banwell B, Joshi RB, He XP, Patry L, Silver RJ, Dobrzeniecka S, Islam MS, Hasnat A, Samuels ME, Aryal DK, Rodriguiz RM, Jiang YH, Wetsel WC, McNamara JO, Rouleau GA, Silver DL, Lancet D, Pras E, Mitchell GA, Michaud JL, Goldstein DB. Deficiency of Asparagine Synthetase Causes Congenital Microcephaly and a Progressive Form of Encephalopathy. Neuron 2013, 80: 429-441. PMID: 24139043, PMCID: PMC3820368, DOI: 10.1016/j.neuron.2013.08.013.Peer-Reviewed Original ResearchConceptsCongenital microcephalyProgressive cerebral atrophyStructural brain abnormalitiesCerebral atrophyNeuronal damageEnhanced excitabilityIntractable seizuresAsparagine depletionNeurological impairmentBrain abnormalitiesCortical thicknessLoss of functionASNS deficiencyProgressive formMutant micePatient phenotypesIntellectual disabilityASNS geneMicrocephalyMissense mutationsBrainDeficiencyAspartate/MutationsRecessive mutationsDetection of Clinically Relevant Genetic Variants in Autism Spectrum Disorder by Whole-Genome Sequencing
Jiang YH, Yuen RK, Jin X, Wang M, Chen N, Wu X, Ju J, Mei J, Shi Y, He M, Wang G, Liang J, Wang Z, Cao D, Carter MT, Chrysler C, Drmic IE, Howe JL, Lau L, Marshall CR, Merico D, Nalpathamkalam T, Thiruvahindrapuram B, Thompson A, Uddin M, Walker S, Luo J, Anagnostou E, Zwaigenbaum L, Ring RH, Wang J, Lajonchere C, Wang J, Shih A, Szatmari P, Yang H, Dawson G, Li Y, Scherer SW. Detection of Clinically Relevant Genetic Variants in Autism Spectrum Disorder by Whole-Genome Sequencing. American Journal Of Human Genetics 2013, 93: 249-263. PMID: 23849776, PMCID: PMC3738824, DOI: 10.1016/j.ajhg.2013.06.012.Peer-Reviewed Original ResearchConceptsWhole-genome sequencingASD risk genesGenetic variantsThorough bioinformatics analysisRisk genesDe novoRelevant genetic variantsBioinformatics analysisDeleterious variantsHigh heritabilityGenomic heterogeneityGenesPutative mutationsMutationsNovo mutationsGenetic causeASD probandsSequencingNovoFamilyCHARGE syndromeVariantsUnreported mutationsCAPRIN1
2012
Mutations of ANK3 identified by exome sequencing are associated with autism susceptibility
Bi C, Wu J, Jiang T, Liu Q, Cai W, Yu P, Cai T, Zhao M, Jiang Y, Sun ZS. Mutations of ANK3 identified by exome sequencing are associated with autism susceptibility. Human Mutation 2012, 33: 1635-1638. PMID: 22865819, DOI: 10.1002/humu.22174.Peer-Reviewed Original ResearchConceptsExtensive bioinformatics analysisNext-generation sequencing technologiesExtreme genetic heterogeneityStrong genetic etiologyGene discoveryWhole-exome sequencesDifferent missense mutationsBioinformatics analysisSequencing technologiesAutism susceptibilityMissense mutationsANK3Genetic heterogeneityMutationsNovo mutationsExome sequencingMolecular pathophysiologyGenetic causeGenetic etiologyASD susceptibilitySynaptic functionNovel mutationsNeurodevelopmental disordersGenesSequencing
2004
EPIGENETICS AND HUMAN DISEASE
Jiang YH, Bressler J, Beaudet AL. EPIGENETICS AND HUMAN DISEASE. Annual Review Of Genomics And Human Genetics 2004, 5: 479-510. PMID: 15485357, DOI: 10.1146/annurev.genom.5.061903.180014.Peer-Reviewed Original ResearchConceptsHuman diseasesComplex disease traitsRole of epigeneticsHeritable changesChromatin structureGenomic imprintingDNA sequencesEpigenetic phenotypesDisease traitsGene expressionImprinting defectsGenetic scansBeckwith-Wiedemann syndromeGenesDisease phenotypeUniparental disomyDe novoEpigeneticsPhenotypeGenetic disordersExpressionChromatinEpimutationsTraitsMutations