2022
Epigenome-wide association study of acute lymphoblastic leukemia in children with Down syndrome
Li S, Sok P, Xu K, Muskens IS, Elliott N, Myint SS, Pandey P, Hansen HM, Morimoto LM, Kang AY, Metayer C, Ma X, Mueller BA, Roy A, Roberts I, Rabin KR, Brown AL, Lupo PJ, Wiemels JL, de Smith AJ. Epigenome-wide association study of acute lymphoblastic leukemia in children with Down syndrome. Blood Advances 2022, 6: 4132-4136. PMID: 35588500, PMCID: PMC9327551, DOI: 10.1182/bloodadvances.2022007098.Peer-Reviewed Original ResearchAccelerated epigenetic aging in newborns with Down syndrome
Xu K, Li S, Muskens IS, Elliott N, Myint SS, Pandey P, Hansen HM, Morimoto LM, Kang AY, Ma X, Metayer C, Mueller BA, Roberts I, Walsh KM, Horvath S, Wiemels JL, de Smith A. Accelerated epigenetic aging in newborns with Down syndrome. Aging Cell 2022, 21: e13652. PMID: 35661546, PMCID: PMC9282838, DOI: 10.1111/acel.13652.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgingAging, PrematureDNA MethylationDown SyndromeEpigenesis, GeneticEpigenomicsHumansInfant, NewbornConceptsDown syndromeAge accelerationEpigenetic age accelerationGestational age accelerationEarly-onset Alzheimer's diseaseTransient abnormal myelopoiesisPotential confounding factorsEpigenetic agingPremature agingSomatic GATA1 mutationsDS patientsAbnormal myelopoiesisBlood cell proportionsNewbornsAlzheimer's diseaseConfounding factorsBrain tissueCell proportionGATA1 mutationsEndocrine systemBloodTargeted sequencingSomatic mutationsSyndromeDisease
2021
The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis
Muskens IS, Li S, Jackson T, Elliot N, Hansen HM, Myint SS, Pandey P, Schraw JM, Roy R, Anguiano J, Goudevenou K, Siegmund KD, Lupo PJ, de Bruijn MFTR, Walsh KM, Vyas P, Ma X, Roy A, Roberts I, Wiemels JL, de Smith AJ. The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis. Nature Communications 2021, 12: 821. PMID: 33547282, PMCID: PMC7865055, DOI: 10.1038/s41467-021-21064-z.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesCore Binding Factor Alpha 2 SubunitCpG IslandsDNA MethylationDown SyndromeEpigenesis, GeneticFemaleFetusGATA1 Transcription FactorGenome, HumanGenome-Wide Association StudyHematopoiesisHematopoietic Stem CellsHumansInfant, NewbornLiverMalePromoter Regions, GeneticProto-Oncogene Protein c-fli-1ConceptsDNA methylationGenome-wide impactGenome-wide effectsGenome-wide perturbationsPromoter/enhancer regionEpigenome-wide association studiesAssociation study resultsGene expression changesHematopoietic stem/progenitor cellsCell-type heterogeneityStem/progenitor cellsEpigenome-wide significant CpGsHematopoietic developmentDifferential methylationEpigenetic changesGene expressionPromoter regionEnhancer regionExpression changesAssociation studiesSignificant CpGsImportant regulatorSignificant hypermethylationHematopoietic cellsMethylation
2019
Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome
Brown AL, de Smith AJ, Gant VU, Yang W, Scheurer ME, Walsh KM, Chernus JM, Kallsen NA, Peyton SA, Davies GE, Ehli EA, Winick N, Heerema NA, Carroll AJ, Borowitz MJ, Wood BL, Carroll WL, Raetz EA, Feingold E, Devidas M, Barcellos LF, Hansen HM, Morimoto L, Kang AY, Smirnov I, Healy J, Laverdière C, Sinnett D, Taub JW, Birch JM, Thompson P, Spector LG, Pombo-de-Oliveira MS, DeWan AT, Mullighan CG, Hunger SP, Pui CH, Loh ML, Zwick ME, Metayer C, Ma X, Mueller BA, Sherman SL, Wiemels JL, Relling MV, Yang JJ, Lupo PJ, Rabin KR. Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome. Blood 2019, 134: 1227-1237. PMID: 31350265, PMCID: PMC6788009, DOI: 10.1182/blood.2018890764.Peer-Reviewed Original ResearchMeSH KeywordsChildCyclin-Dependent Kinase Inhibitor p16DNA-Binding ProteinsDown SyndromeGATA3 Transcription FactorGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIkaros Transcription FactorPolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaTranscription FactorsConceptsFirst genome-wide association studySusceptibility lociGenome-wide association studiesGenome-wide significanceFurther biological insightsGenetic variationEnhancer activityRisk lociBiological insightsLymphoblastoid cell linesAssociation studiesDifferential protein bindingFunctional significanceLociRisk allele frequenciesCell linesAllele frequenciesHigh penetranceRisk allelesProtein bindingCDKN2AGenetic susceptibilityHigher proliferationPenetranceAllele associationsHeritable variation at the chromosome 21 gene ERG is associated with acute lymphoblastic leukemia risk in children with and without Down syndrome
de Smith AJ, Walsh KM, Morimoto LM, Francis SS, Hansen HM, Jeon S, Gonseth S, Chen M, Sun H, Luna-Fineman S, Antillón F, Girón V, Kang AY, Smirnov I, Shao X, Whitehead TP, Barcellos LF, Jolly KW, Healy J, Laverdière C, Sinnett D, Taub JW, Birch JM, Thompson PD, Pombo-de-Oliveira MS, Spector LG, DeWan AT, Mueller BA, Chiang C, Metayer C, Ma X, Wiemels JL. Heritable variation at the chromosome 21 gene ERG is associated with acute lymphoblastic leukemia risk in children with and without Down syndrome. Leukemia 2019, 33: 2746-2751. PMID: 31296947, PMCID: PMC6858994, DOI: 10.1038/s41375-019-0514-9.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentCaliforniaCase-Control StudiesChildChild, PreschoolChromosomes, Human, Pair 21Down SyndromeFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGuatemalaHaplotypesHispanic or LatinoHumansInfantInfant, NewbornMalePolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaPrincipal Component AnalysisRisk FactorsTranscriptional Regulator ERG