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, 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
2021
Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate Reporter Gene Expression in Human Immune Cells
Jagoda E, Xue JR, Reilly SK, Dannemann M, Racimo F, Huerta-Sanchez E, Sankararaman S, Kelso J, Pagani L, Sabeti PC, Capellini TD. Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate Reporter Gene Expression in Human Immune Cells. Molecular Biology And Evolution 2021, 39: msab304. PMID: 34662402, PMCID: PMC8760939, DOI: 10.1093/molbev/msab304.Peer-Reviewed Original ResearchConceptsCis-regulatory elementsGene expressionPutative cis-regulatory elementsParallel reporter assaysImmune transcription factorsReporter gene expressionExpression of genesGenic targetsSelective sweepsMPRA dataInnate immune pathwaysPositive selectionTranscription factorsEndogenous sequencesReporter assaysAntiviral defenseDriver variantsGenetic variantsFunctional significanceImmune pathwaysWhite blood cell countGenesModern humansPotential immune responseBlood cell countGenome-wide functional screen of 3′UTR variants uncovers causal variants for human disease and evolution
Griesemer D, Xue JR, Reilly SK, Ulirsch JC, Kukreja K, Davis JR, Kanai M, Yang DK, Butts JC, Guney MH, Luban J, Montgomery SB, Finucane HK, Novina CD, Tewhey R, Sabeti PC. Genome-wide functional screen of 3′UTR variants uncovers causal variants for human disease and evolution. Cell 2021, 184: 5247-5260.e19. PMID: 34534445, PMCID: PMC8487971, DOI: 10.1016/j.cell.2021.08.025.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesCausal variantsEvolutionary adaptationGenome-wide functional screenDiverse molecular mechanismsHuman evolutionary adaptationBase-pair resolutionParallel reporterHuman cell linesMiRNA sitesTranscriptional changesFunctional screenAllelic replacementSimple sequenceMolecular mechanismsAssociation studiesRich elementsPair resolutionHuman diseasesPhenotype associationsHuman traitsUntranslated region variantsGenetic variantsRegulatory activityCell lines
2020
Prioritizing 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