Show simple item record

dc.creatorLu, Xiaoming 
dc.creatorZoller, Erin E. 
dc.creatorWeirauch, Matthew T. 
dc.creatorWu, Zhiguo 
dc.creatorNamjou, Bahram 
dc.creatorWilliams, Adrienne H. 
dc.creatorZiegler, Julie T. 
dc.creatorComeau, Mary E. 
dc.creatorMarion, Miranda C. 
dc.creatorGlenn, Stuart B. 
dc.creatorAdler, Adam 
dc.creatorShen, Nan 
dc.creatorNath, Swapan K. 
dc.creatorStevens, Anne M. 
dc.creatorFreedman, Barry I. 
dc.creatorTsao, Betty P. 
dc.creatorJacob, Chaim O. 
dc.creatorKamen, Diane L. 
dc.creatorBrown, Elizabeth E. 
dc.creatorGilkeson, Gary S. 
dc.creatorAlarcón, Graciela S. 
dc.creatorReveille, John D. 
dc.creatorAnaya, Juan-Manuel 
dc.creatorJames, Judith A. 
dc.creatorSivils, Kathy L. 
dc.creatorCriswell, Lindsey A. 
dc.creatorVilá, Luis M. 
dc.creatorAlarcón-Riquelme, Marta E. 
dc.creatorPetri, Michelle 
dc.creatorScofield, R. Hal 
dc.creatorKimberly, Robert P. 
dc.creatorRamsey-Goldman, Rosalind 
dc.creatorBin Joo, Young 
dc.creatorChoi, Jeongim 
dc.creatorBae, Sang-Cheol 
dc.creatorBoackle, Susan A. 
dc.creatorGraham, Deborah Cunninghame 
dc.creatorVyse, Timothy J. 
dc.creatorGuthridge, Joel M. 
dc.creatorGaffney, Patrick M. 
dc.creatorLangefeld, Carl D. 
dc.creatorKelly, Jennifer A. 
dc.creatorGreis, Kenneth D. 
dc.creatorKaufman, Kenneth M. 
dc.creatorHarley, John B. 
dc.creatorKottyan, Leah C. 
dc.date.accessioned2020-05-26T00:09:10Z
dc.date.available2020-05-26T00:09:10Z
dc.date.created2015
dc.identifier.issn15376605
dc.identifier.issn00029297
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/24141
dc.description.abstract"Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been associated with systemic lupus erythematosus (SLE), or lupus, in independent cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a critical driver of immune cell function and differentiation, and mice deficient in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of 14,551 subjects from multi-ancestral cohorts by starting with genotyped variants and imputing to all common variants spanning ETS1. By constructing genetic models via frequentist and Bayesian association methods, we identified 16 variants that are statistically likely to be causal. We functionally assessed each of these variants on the basis of their likelihood of affecting transcription factor binding, miRNA binding, or chromatin state. Of the four variants that we experimentally examined, only rs6590330 differentially binds lysate from B cells. Using mass spectrometry, we found more binding of the transcription factor signal transducer and activator of transcription 1 (STAT1) to DNA near the risk allele of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed that the risk allele increased binding to the active form of STAT1. Analysis with expression quantitative trait loci indicated that the risk allele of rs6590330 is associated with decreased ETS1 expression in Han Chinese, but not other ancestral cohorts. We propose a model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1. © 2015 by The American Society of Human Genetics. All rights reserved."
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.relation.ispartofAmerican Journal of Human Genetics, ISSN:15376605, 00029297, Vol.96, No.5 (2015); pp. 731-739
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84929276935&doi=10.1016%2fj.ajhg.2015.03.002&partnerID=40&md5=0e6648d7e12d56710ee06807ce1fd6bf
dc.sourceinstname:Universidad del Rosario
dc.sourcereponame:Repositorio Institucional EdocUR
dc.titleLupus risk variant increases pSTAT1 binding and decreases ETS1 expression
dc.typearticle
dc.publisherCell Press
dc.subject.keywordDna
dc.subject.keywordsystemic
dc.subject.keywordMicrorna
dc.subject.keywordhuman
dc.subject.keywordStat1 protein
dc.subject.keywordTranscription factor
dc.subject.keywordTranscription factor ets 1
dc.subject.keywordEts1 protein
dc.subject.keywordProtein binding
dc.subject.keywordStat1 protein
dc.subject.keywordTranscription factor ets 1
dc.subject.keywordAllele
dc.subject.keywordArticle
dc.subject.keywordAsian
dc.subject.keywordAutoimmunity
dc.subject.keywordB lymphocyte
dc.subject.keywordBayesian learning
dc.subject.keywordChromatin
dc.subject.keywordChromatin immunoprecipitation
dc.subject.keywordGene locus
dc.subject.keywordGene mapping
dc.subject.keywordGenetic model
dc.subject.keywordGenetic risk
dc.subject.keywordGenetic variability
dc.subject.keywordGenotype
dc.subject.keywordHan chinese
dc.subject.keywordHuman
dc.subject.keywordImmunoblotting
dc.subject.keywordMass spectrometry
dc.subject.keywordModel
dc.subject.keywordPriority journal
dc.subject.keywordProtein binding
dc.subject.keywordSystemic lupus erythematosus
dc.subject.keywordAnimal
dc.subject.keywordAsian continental ancestry group
dc.subject.keywordBayes theorem
dc.subject.keywordGenetic predisposition
dc.subject.keywordGenetics
dc.subject.keywordHaplotype
dc.subject.keywordMetabolism
dc.subject.keywordMouse
dc.subject.keywordSystemic lupus erythematosus
dc.subject.keywordMus
dc.subject.keywordAlleles
dc.subject.keywordAnimals
dc.subject.keywordAsian continental ancestry group
dc.subject.keywordBayes theorem
dc.subject.keywordGenetic predisposition to disease
dc.subject.keywordGenotype
dc.subject.keywordHaplotypes
dc.subject.keywordHumans
dc.subject.keywordLupus erythematosus
dc.subject.keywordMice
dc.subject.keywordProtein binding
dc.subject.keywordProto-oncogene protein c-ets-1
dc.subject.keywordStat1 transcription factor
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.type.spaArtículo
dc.rights.accesoAbierto (Texto Completo)
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doihttps://doi.org/10.1016/j.ajhg.2015.03.002
dc.relation.citationEndPage739
dc.relation.citationIssueNo. 5
dc.relation.citationStartPage731
dc.relation.citationTitleAmerican Journal of Human Genetics
dc.relation.citationVolumeVol. 96


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record