2021
Direct characterization of cis-regulatory elements and functional dissection of complex genetic associations using HCR–FlowFISH
Reilly SK, Gosai SJ, Gutierrez A, Mackay-Smith A, Ulirsch JC, Kanai M, Mouri K, Berenzy D, Kales S, Butler GM, Gladden-Young A, Bhuiyan RM, Stitzel ML, Finucane HK, Sabeti PC, Tewhey R. Direct characterization of cis-regulatory elements and functional dissection of complex genetic associations using HCR–FlowFISH. Nature Genetics 2021, 53: 1166-1176. PMID: 34326544, PMCID: PMC8925018, DOI: 10.1038/s41588-021-00900-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingBayes TheoremClustered Regularly Interspaced Short Palindromic RepeatsDelta-5 Fatty Acid DesaturaseDeoxyribonuclease IFatty Acid DesaturasesFlow CytometryGATA1 Transcription FactorHumansIn Situ Hybridization, FluorescenceK562 CellsLIM Domain ProteinsModels, GeneticPolymorphism, Single NucleotideProto-Oncogene ProteinsQuantitative Trait LociRegulatory Sequences, Nucleic AcidRNA, Guide, CRISPR-Cas SystemsConceptsCis-regulatory elementsGenome-wide association signalsGenome functionEpigenetic mappingComplex genetic associationsFunctional dissectionNearest geneGenetic variationAssociation signalsNative transcriptsTarget genesCausal variantsMultiple genesEndogenous functionsReporter assaysGenesCre activitySitu hybridizationGenetic associationFlow cytometryLociTranscriptsHierarchical Bayesian modelReaction fluorescenceHybridization
2020
Massively parallel discovery of human-specific substitutions that alter enhancer activity
Uebbing S, Gockley J, Reilly SK, Kocher AA, Geller E, Gandotra N, Scharfe C, Cotney J, Noonan JP. Massively parallel discovery of human-specific substitutions that alter enhancer activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 118: e2007049118. PMID: 33372131, PMCID: PMC7812811, DOI: 10.1073/pnas.2007049118.Peer-Reviewed Original ResearchConceptsHuman-specific substitutionsHuman-gained enhancersGenetic changesEnhancer functionEnhancer activityHuman-specific genetic changesHuman evolutionGene regulatory elementsBackground genetic variationAncestral functionRegulatory evolutionEnhancer assaysGenetic variationRegulatory elementsNeural stem cellsHuman traitsNovel activityNonadditive wayRegulatory activityStem cellsFunctional impactDifferential activityParallel discoveryEnhancerEvolutionPrioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features
Ray JP, de Boer CG, Fulco CP, Lareau CA, Kanai M, Ulirsch JC, Tewhey R, Ludwig LS, Reilly SK, Bergman DT, Engreitz JM, Issner R, Finucane HK, Lander ES, Regev A, Hacohen N. Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features. Nature Communications 2020, 11: 1237. PMID: 32144282, PMCID: PMC7060350, DOI: 10.1038/s41467-020-15022-4.Peer-Reviewed Original ResearchConceptsChromatin accessible regionsGenome-wide association studiesDisease-associated lociGenetic variantsCausal genetic variantsDisease-associated variantsComplex traitsGenetic variationRegulatory regionsGenomic featuresCausal variantsRegulatory potentialAssociation studiesReporter activityDisease-associated haplotypeLinkage disequilibriumCommon variantsTight linkage disequilibriumExperimental assaysCell linesImmune cell linesLociAccessible regionsTNFAIP3TNFAIP3 locus