2024
Resolving the 22q11.2 deletion using CTLR-Seq reveals chromosomal rearrangement mechanisms and individual variance in breakpoints
Zhou B, Purmann C, Guo H, Shin G, Huang Y, Pattni R, Meng Q, Greer S, Roychowdhury T, Wood R, Ho M, Dohna H, Abyzov A, Hallmayer J, Wong W, Ji H, Urban A. Resolving the 22q11.2 deletion using CTLR-Seq reveals chromosomal rearrangement mechanisms and individual variance in breakpoints. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2322834121. PMID: 39042694, PMCID: PMC11295037, DOI: 10.1073/pnas.2322834121.Peer-Reviewed Original ResearchConceptsLong-read sequencingPulse-field gel electrophoresisBase-pair resolutionDNA methylation patternsCell-type specific analysisCell type-specificChromosomal interactionsSequence assemblySegmental duplicationsGenome sequenceGenomic rearrangementsGenomic regionsChromosomal breakpointsHuman genomeGenomic recombinationMethylation patternsSequence analysisHaplotype-specificDeletion haplotypesGel electrophoresisGenomeAmplification-freeBreakpoint locationsMicrodeletion disorderType-specific
2021
Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm
Roychowdhury T, Lu H, Hornsby WE, Crone B, Wang GT, Guo DC, Sendamarai AK, Devineni P, Lin M, Zhou W, Graham SE, Wolford BN, Surakka I, Wang Z, Chang L, Zhang J, Mathis M, Brummett CM, Melendez TL, Shea MJ, Kim KM, Deeb GM, Patel HJ, Eliason J, Eagle KA, Yang B, Ganesh SK, Brumpton B, Åsvold BO, Skogholt AH, Hveem K, Program V, Pyarajan S, Klarin D, Tsao PS, Damrauer SM, Leal SM, Milewicz DM, Chen YE, Garcia-Barrio MT, Willer CJ. Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm. American Journal Of Human Genetics 2021, 108: 1578-1589. PMID: 34265237, PMCID: PMC8456156, DOI: 10.1016/j.ajhg.2021.06.016.Peer-Reviewed Original ResearchMeSH KeywordsAortaAortic Aneurysm, ThoracicBcl-2-Associated X ProteinCase-Control StudiesCaspase 3Diabetes Mellitus, Type 2Endothelial CellsGene Expression RegulationGenome, HumanGenome-Wide Association StudyHumansIntronsMichiganMuscle, Smooth, VascularMutationProto-Oncogene Proteins c-bcl-2Quantitative Trait LociTranscription Factor 7-Like 2 ProteinConceptsGenome-wide significant associationDifferent causal variantsGenome-wide scanCommon variantsVascular smooth muscle cell apoptosisSmooth muscle cell apoptosisMuscle cell apoptosisRegulatory variantsGenomics initiativesSingle geneThird intronCausal variantsMichigan Genomics InitiativeHeritable diseaseType 2 diabetesCell apoptosisGenetic associationAdditional independent cohortsTCF7L2Aortic aneurysmLociHigh expressionTAAGenetic risk factorsFunctional relationship
2020
Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease
Nielsen JB, Rom O, Surakka I, Graham SE, Zhou W, Roychowdhury T, Fritsche LG, Gagliano Taliun SA, Sidore C, Liu Y, Gabrielsen ME, Skogholt AH, Wolford B, Overton W, Zhao Y, Chen J, Zhang H, Hornsby WE, Acheampong A, Grooms A, Schaefer A, Zajac GJM, Villacorta L, Zhang J, Brumpton B, Løset M, Rai V, Lundegaard PR, Olesen MS, Taylor KD, Palmer ND, Chen YD, Choi SH, Lubitz SA, Ellinor PT, Barnes KC, Daya M, Rafaels N, Weiss ST, Lasky-Su J, Tracy RP, Vasan RS, Cupples LA, Mathias RA, Yanek LR, Becker LC, Peyser PA, Bielak LF, Smith JA, Aslibekyan S, Hidalgo BA, Arnett DK, Irvin MR, Wilson JG, Musani SK, Correa A, Rich SS, Guo X, Rotter JI, Konkle BA, Johnsen JM, Ashley-Koch AE, Telen MJ, Sheehan VA, Blangero J, Curran JE, Peralta JM, Montgomery C, Sheu WH, Chung RH, Schwander K, Nouraie SM, Gordeuk VR, Zhang Y, Kooperberg C, Reiner AP, Jackson RD, Bleecker ER, Meyers DA, Li X, Das S, Yu K, LeFaive J, Smith A, Blackwell T, Taliun D, Zollner S, Forer L, Schoenherr S, Fuchsberger C, Pandit A, Zawistowski M, Kheterpal S, Brummett CM, Natarajan P, Schlessinger D, Lee S, Kang HM, Cucca F, Holmen OL, Åsvold BO, Boehnke M, Kathiresan S, Abecasis GR, Chen YE, Willer CJ, Hveem K. Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease. Nature Communications 2020, 11: 6417. PMID: 33339817, PMCID: PMC7749177, DOI: 10.1038/s41467-020-20086-3.Peer-Reviewed Original ResearchConceptsCardiovascular diseaseProtein-altering variantsNon-fasting blood glucoseFatty liver diseaseMore cardiovascular diseasesPotential therapeutic targetNovel candidate drug targetsDrug targetsLipoprotein cholesterolLiver diseaseLiver functionHUNT StudyBlood glucoseLiver enzymesMetabolic disordersCandidate drug targetsTherapeutic targetLDL uptakeLDL receptorDiseaseHepatoma cells resultsAdverse effectsBlood traitsDyslipidemiaBeneficial impact
2019
Chromatin organization modulates the origin of heritable structural variations in human genome
Roychowdhury T, Abyzov A. Chromatin organization modulates the origin of heritable structural variations in human genome. Nucleic Acids Research 2019, 47: 2766-2777. PMID: 30773596, PMCID: PMC6451188, DOI: 10.1093/nar/gkz103.Peer-Reviewed Original Research
2017
Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis
Bae T, Tomasini L, Mariani J, Zhou B, Roychowdhury T, Franjic D, Pletikos M, Pattni R, Chen BJ, Venturini E, Riley-Gillis B, Sestan N, Urban AE, Abyzov A, Vaccarino FM. Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science 2017, 359: 550-555. PMID: 29217587, PMCID: PMC6311130, DOI: 10.1126/science.aan8690.Peer-Reviewed Original ResearchConceptsSingle nucleotide variationsMutation rateCancer cell genomeClonal cell populationsCell genomeCell lineagesBackground mutagenesisHuman cellsMutational rateSomatic mosaicismSingle cellsOxidative damageGenomeMutagenesisCell populationsMutation spectrumNeurogenesisCellsHuman fetusesIndividual neuronsLineagesPregastrulationHuman brainBrainMutations