2019
DNA 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 ResearchMeSH KeywordsAutism Spectrum DisorderDNA MethylationEpigenesis, GeneticFemaleGenetic Predisposition to DiseaseHumansIncidenceMalePrognosisRisk AssessmentSequence Analysis, DNAConceptsDNA methylationAbnormal DNA methylationDNA methylation reprogrammingGenome-wide changesMethylation-dependent regulationMethylation reprogrammingEpigenetic machineryNext-generation sequencingEmbryonic developmentMolecular basisDNA modificationsMethylationASD etiologyGenetic mutationsAttractive hypothesisRecent advancesReprogrammingEpimutationsTranscriptionASD casesMultiple levelsMachinerySequencingTechnical advancesMutations
2018
Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing
Wu J, Yu P, Jin X, Xu X, Li J, Li Z, Wang M, Wang T, Wu X, Jiang Y, Cai W, Mei J, Min Q, Xu Q, Zhou B, Guo H, Wang P, Zhou W, Hu Z, Li Y, Cai T, Wang Y, Xia K, Jiang YH, Sun ZS. Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing. Journal Of Genetics And Genomics 2018, 45: 527-538. PMID: 30392784, DOI: 10.1016/j.jgg.2018.09.002.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdolescentAdultAsian PeopleAutism Spectrum DisorderCell Cycle ProteinsChildChild, PreschoolChinaDNA Copy Number VariationsDNA-Binding ProteinsFemaleGenetic Predisposition to DiseaseHumansMaleMutationNerve Tissue ProteinsTranscription FactorsWhole Genome SequencingYoung AdultConceptsChromosomal rearrangement eventsDe novo chromosomal translocationsGenomic structural variantsNovo chromosomal translocationWhole genome sequencing datasetsFull genetic spectrumRare deleterious variantsChromosomal structure analysisHigh mutation rateSporadic autism spectrum disordersWhole-genome sequencingChromatin remodelingCentrosomal functionWhole genomeRare inherited mutationsDe novo mutationsRearrangement eventsSequencing datasetsDeleterious variantsGenomic variantsMutation rateStructural variantsGenomic landscapeNovo CNVsRisk genesA comprehensive iterative approach is highly effective in diagnosing individuals who are exome negative
Shashi V, Schoch K, Spillmann R, Cope H, Tan Q, Walley N, Pena L, McConkie-Rosell A, Jiang YH, Stong N, Need AC, Goldstein DB. A comprehensive iterative approach is highly effective in diagnosing individuals who are exome negative. Genetics In Medicine 2018, 21: 161-172. PMID: 29907797, PMCID: PMC6295275, DOI: 10.1038/s41436-018-0044-2.Peer-Reviewed Original ResearchEpigenetics 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 ResearchMeSH KeywordsAutism Spectrum DisorderAutistic DisorderChildEpigenesis, GeneticEpigenomicsExome SequencingGenetic Predisposition to DiseaseHistonesHumansMaleMutationConceptsLinker 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
Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases
Pena LDM, Jiang YH, Schoch K, Spillmann RC, Walley N, Stong N, Rapisardo Horn S, Sullivan JA, McConkie-Rosell A, Kansagra S, Smith EC, El-Dairi M, Bellet J, Keels MA, Jasien J, Kranz PG, Noel R, Nagaraj SK, Lark RK, Wechsler DSG, del Gaudio D, Leung ML, Hendon LG, Parker CC, Jones KL, Goldstein D, Shashi V. Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases. Genetics In Medicine 2017, 20: 464-469. PMID: 28914269, PMCID: PMC5851806, DOI: 10.1038/gim.2017.128.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMagnetic resonance image changesPathogenic variantsSanger sequencingPhenotype-first approachFurther diagnostic testingNew clinical findingsInfantile neuroaxonal dystrophyHeterozygous pathogenic variantsInfantile systemic hyalinosisSingle-gene testingClinical suspicionClinical findingsConclusionThese casesCerebellar atrophyWhite matter leukoencephalopathyNeuroaxonal dystrophyProgressive ataxiaMolecular testingSystemic hyalinosisNGS testingNovel homozygous deletionUndiagnosed diseaseClinical diagnosisDiagnostic testingGenetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing
Wang Y, Du X, Bin R, Yu S, Xia Z, Zheng G, Zhong J, Zhang Y, Jiang YH, Wang Y. Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing. Scientific Reports 2017, 7: 40319. PMID: 28074849, PMCID: PMC5225856, DOI: 10.1038/srep40319.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceChildEpilepsyExome SequencingFemaleGenetic Predisposition to DiseaseGenetic VariationHumansInfantMaleMutationPedigreePolymorphism, Single NucleotideReproducibility of ResultsConceptsNGS panelCaucasian childrenEtiology of epilepsyLikely pathogenic variantsTargeted exome sequencingGenetic variantsSingle nucleotide variantsUnknown etiologyEpilepsy patientsSpecific treatmentEpilepsyEpilepsy disordersPathogenic variantsPathologic variantsGenetic susceptibilityEpilepsy genesExome sequencingEtiologyGenetic factorsEpilepsy familiesChinese childrenCandidate genesClinicNovel candidate genesChildren
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 ResearchMeSH KeywordsAdolescentAnimalsAspartate-Ammonia LigaseAtrophyBrainChildFemaleGenetic Predisposition to DiseaseHumansInfantInfant, NewbornIntellectual DisabilityMaleMiceMice, TransgenicMicrocephalyMutation, MissensePedigreeSyndromeConceptsCongenital 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 ResearchMeSH KeywordsAdultChildChild Development Disorders, PervasiveFemaleGenetic HeterogeneityGenetic Predisposition to DiseaseGenomeHigh-Throughput Nucleotide SequencingHumansMaleMutationPedigreeConceptsWhole-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
Human disorders of ubiquitination and proteasomal degradation
Jiang YH, Beaudet AL. Human disorders of ubiquitination and proteasomal degradation. Current Opinion In Pediatrics 2004, 16: 419-426. PMID: 15273504, DOI: 10.1097/01.mop.0000133634.79661.cd.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAngelman SyndromeAnimalsFanconi AnemiaGenetic Diseases, InbornGenetic Predisposition to DiseaseHumansNF-kappa BPolyendocrinopathies, AutoimmuneProteasome Endopeptidase ComplexUbiquitin-Activating EnzymesUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesUbiquitinsVon Hippel-Lindau DiseaseConceptsProteasomal degradationProteasomal subunitsAdditional functional classesUbiquitin E3 ligaseAutosomal recessive juvenile Parkinson's diseaseUbiquitin signalingE3 ligasesUbiquitin pathwayGenetic inborn errorsUbiquitin genesE3 ligaseSubcellular localizationUbiquitinationRelated proteinsMultiple functional defectsRelevant genesHuman disordersCongenital polycythemiaRegulatory signalingFanconi anemiaGenetic classesOvarian cancer susceptibilityFunctional classificationProteolytic degradationUbiquitin