2024
Massively parallel approaches for characterizing noncoding functional variation in human evolution
Rong S, Root E, Reilly S. Massively parallel approaches for characterizing noncoding functional variation in human evolution. Current Opinion In Genetics & Development 2024, 88: 102256. PMID: 39217658, PMCID: PMC11648527, DOI: 10.1016/j.gde.2024.102256.Peer-Reviewed Original ResearchCis-regulatory elementsFunction of cis-regulatory elementsImpact of sequence variantsHigh-throughput approachNoncoding variationGenome functionNoncoding regionsSequence variantsPhenotypic consequencesCRISPR screensGenetic basisGenetic variantsGenetic differencesDiverse phenotypesGene expressionRegulatory functionsHuman evolutionFunctional variationGenomeUnique phenotypePhenotypeRegulatory impactModel systemVariantsGenes
2023
Evolutionary constraint and innovation across hundreds of placental mammals
Christmas M, Kaplow I, Genereux D, Dong M, Hughes G, Li X, Sullivan P, Hindle A, Andrews G, Armstrong J, Bianchi M, Breit A, Diekhans M, Fanter C, Foley N, Goodman D, Goodman L, Keough K, Kirilenko B, Kowalczyk A, Lawless C, Lind A, Meadows J, Moreira L, Redlich R, Ryan L, Swofford R, Valenzuela A, Wagner F, Wallerman O, Brown A, Damas J, Fan K, Gatesy J, Grimshaw J, Johnson J, Kozyrev S, Lawler A, Marinescu V, Morrill K, Osmanski A, Paulat N, Phan B, Reilly S, Schäffer D, Steiner C, Supple M, Wilder A, Wirthlin M, Xue J, Birren B, Gazal S, Hubley R, Koepfli K, Marques-Bonet T, Meyer W, Nweeia M, Sabeti P, Shapiro B, Smit A, Springer M, Teeling E, Weng Z, Hiller M, Levesque D, Lewin H, Murphy W, Navarro A, Paten B, Pollard K, Ray D, Ruf I, Ryder O, Pfenning A, Lindblad-Toh K, Karlsson E, Andrews G, Armstrong J, Bianchi M, Birren B, Bredemeyer K, Breit A, Christmas M, Clawson H, Damas J, Di Palma F, Diekhans M, Dong M, Eizirik E, Fan K, Fanter C, Foley N, Forsberg-Nilsson K, Garcia C, Gatesy J, Gazal S, Genereux D, Goodman L, Grimshaw J, Halsey M, Harris A, Hickey G, Hiller M, Hindle A, Hubley R, Hughes G, Johnson J, Juan D, Kaplow I, Karlsson E, Keough K, Kirilenko B, Koepfli K, Korstian J, Kowalczyk A, Kozyrev S, Lawler A, Lawless C, Lehmann T, Levesque D, Lewin H, Li X, Lind A, Lindblad-Toh K, Mackay-Smith A, Marinescu V, Marques-Bonet T, Mason V, Meadows J, Meyer W, Moore J, Moreira L, Moreno-Santillan D, Morrill K, Muntané G, Murphy W, Navarro A, Nweeia M, Ortmann S, Osmanski A, Paten B, Paulat N, Pfenning A, Phan B, Pollard K, Pratt H, Ray D, Reilly S, Rosen J, Ruf I, Ryan L, Ryder O, Sabeti P, Schäffer D, Serres A, Shapiro B, Smit A, Springer M, Srinivasan C, Steiner C, Storer J, Sullivan K, Sullivan P, Sundström E, Supple M, Swofford R, Talbot J, Teeling E, Turner-Maier J, Valenzuela A, Wagner F, Wallerman O, Wang C, Wang J, Weng Z, Wilder A, Wirthlin M, Xue J, Zhang X. Evolutionary constraint and innovation across hundreds of placental mammals. Science 2023, 380: eabn3943. PMID: 37104599, PMCID: PMC10250106, DOI: 10.1126/science.abn3943.Peer-Reviewed Original ResearchConceptsEncyclopedia of DNA ElementsProtein-coding exonsUltraconserved elementsGenome functionGenomic resourcesOrganismal phenotypesDNA elementsFunctional annotationEvolutionary constraintsHuman genomeRegulatory elementsMammalian traitsGenomeGenetic variantsPlacental mammalsTherapeutic developmentMammalsSpeciesDisease riskExonGenesBiodiversityPhenotypeTraitsRepeats
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