{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:52:37Z","timestamp":1791215557331,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2008,8,7]],"date-time":"2008-08-07T00:00:00Z","timestamp":1218067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2008,8,7]],"date-time":"2008-08-07T00:00:00Z","timestamp":1218067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genes Immun"],"published-print":{"date-parts":[[2008,12]]},"DOI":"10.1038\/gene.2008.63","type":"journal-article","created":{"date-parts":[[2008,8,7]],"date-time":"2008-08-07T11:17:54Z","timestamp":1218107874000},"page":"689-696","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Expression levels of FAS are regulated through an evolutionary conserved element in intron 2, which modulates cystic fibrosis disease severity"],"prefix":"10.1038","volume":"9","author":[{"given":"V","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"van Barneveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Boztug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"W\u00f6lfl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"T\u00fcmmler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Stanke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2008,8,7]]},"reference":[{"key":"BFgene200863_CR1","volume-title":"Cystic Fibrosis in the 21st Century","author":"A Bush","year":"2006","unstructured":"Bush A, Alton EWFW, Davies JC, Groesenbach U, Jaffe A . Cystic Fibrosis in the 21st Century 2006 Karger: Basel."},{"key":"BFgene200863_CR2","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1007\/BF02428304","volume":"85","author":"European Working Group on Cystic Fibrosis Genetics","year":"1990","unstructured":"European Working Group on Cystic Fibrosis Genetics. Gradient of distribution in Europe of the major CF mutation and of its associated haplotype. Hum Genet 1990; 85: 436\u2013445.","journal-title":"Hum Genet"},{"key":"BFgene200863_CR3","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/0140-6736(91)92449-C","volume":"337","author":"HK Johannsen","year":"1991","unstructured":"Johannsen HK, Nir M, Hoiby N, Koch C, Schwartz M . Severity of cystic fibrosis in patients homozygous and heterozygous for the deltaF508 mutation. Lancet 1991; 337: 631\u2013634.","journal-title":"Lancet"},{"key":"BFgene200863_CR4","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1375\/136905200320565256","volume":"3","author":"F Mekus","year":"2000","unstructured":"Mekus F, Ballmann M, Bronsveld I, Bijman J, Veeze H, T\u00fcmmler B . Categories of deltaF508 homozygous cystic fibrosis twin and sibling pairs with distinct phenotypic characteristics. Twin Res 2000; 3: 277\u2013293.","journal-title":"Twin Res"},{"key":"BFgene200863_CR5","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1378\/chest.07-1631","volume":"133","author":"A Elizur","year":"2008","unstructured":"Elizur A, Cannon CL, Ferkol TW . Airway inflammation in cystic fibrosis. Chest 2008; 133: 489\u2013495.","journal-title":"Chest"},{"key":"BFgene200863_CR6","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.molmed.2007.05.001","volume":"13","author":"RC Boucher","year":"2007","unstructured":"Boucher RC . Cystic fibrosis: a disease of vulnerability to airway surface dehydration. Trends Mol Med 2007; 13: 231\u2013240.","journal-title":"Trends Mol Med"},{"issue":"Suppl 1","key":"BFgene200863_CR7","doi-asserted-by":"publisher","first-page":"S40","DOI":"10.1007\/s004240100642","volume":"443","author":"O Tabary","year":"2001","unstructured":"Tabary O, Escotte S, Couetil JP, Hubert D, Dusser D, Puchelle E et al. Relationship between IkappaBa deficiency, NFkappaB activity and interleukin-8 production in CF human airway epithelial cells. Pfl\u00fcgers Arch 2001; 443 (Suppl 1): S40\u2013S44.","journal-title":"Pfl\u00fcgers Arch"},{"key":"BFgene200863_CR8","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/j.jaci.2006.01.052","volume":"117","author":"A Saadane","year":"2006","unstructured":"Saadane A, Soltys J, Berger M . Acute Pseudomonas challenge in cystic fibrosis mice causes prolonged nuclear factor-kappa B activation, cytokine secretion, and persistent lung inflammation. J Allergy Clin Immunol 2006; 117: 1163\u20131169.","journal-title":"J Allergy Clin Immunol"},{"key":"BFgene200863_CR9","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/nm1748","volume":"14","author":"V Teichgr\u00e4ber","year":"2008","unstructured":"Teichgr\u00e4ber V, Ulrich M, Endlich N, Riethm\u00fcller J, Wilker B, De Oliveira-Munding CC et al. Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat Med 2008; 14: 382\u2013391.","journal-title":"Nat Med"},{"key":"BFgene200863_CR10","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/S0014-5793(97)00347-5","volume":"408","author":"L Maiuri","year":"1997","unstructured":"Maiuri L, Raia V, De Marco G, Coletta S, de Ritis G, Londei M et al. DNA fragmentation is a feature of cystic fibrosis epithelial cells: a disease with inappropriate apoptosis? FEBS Lett 1997; 408: 225\u2013231.","journal-title":"FEBS Lett"},{"key":"BFgene200863_CR11","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1165\/rcmb.4898","volume":"29","author":"CL Cannon","year":"2003","unstructured":"Cannon CL, Kowalski MP, Stopak KS, Pier GB . Pseudomonas aeruginosa\u2014induced apoptosis is defective in respiratory epithelial cells expressing mutatnt cystic fibrosis transmembrane conductance regulator. Am J Respir Cell Mol Biol 2003; 29: 188\u2013197.","journal-title":"Am J Respir Cell Mol Biol"},{"key":"BFgene200863_CR12","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1146\/annurev.genet.33.1.29","volume":"33","author":"S Nagata","year":"1999","unstructured":"Nagata S . FAS-ligand induced apoptosis. Annu Rev Genet 1999; 33: 29\u201355.","journal-title":"Annu Rev Genet"},{"key":"BFgene200863_CR13","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1126\/science.290.5491.527","volume":"290","author":"H Grassme","year":"2000","unstructured":"Grassme H, Kirschnek S, Riethmueller J, Riehle A, von K\u00fcrthy G, Lang F et al. CD95\/CD95 ligand interactions on epithelial cells in host defense to Pseudomonas aeruginosa. Science 2000; 290: 527\u2013530.","journal-title":"Science"},{"key":"BFgene200863_CR14","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s00439-006-0140-2","volume":"119","author":"F Stanke","year":"2006","unstructured":"Stanke F, Becker T, Cuppens H, Kumar V, Cassiman JJ, Jansen S et al. The TNFalpha receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis. Hum Genet 2006; 119: 331\u2013343.","journal-title":"Hum Genet"},{"issue":"Web Server issu","key":"BFgene200863_CR15","doi-asserted-by":"publisher","first-page":"W273","DOI":"10.1093\/nar\/gkh458","volume":"32","author":"KA Frazer","year":"2004","unstructured":"Frazer KA, Pachter L, Poliakov A, Rubin EM, Dubchak I . VISTA: computational tools for comparative genomics. Nucleic Acids Res 2004; 32 (Web Server issue): W273\u2013W279.","journal-title":"Nucleic Acids Res"},{"key":"BFgene200863_CR16","doi-asserted-by":"publisher","first-page":"3819","DOI":"10.1093\/nar\/gkg562","volume":"31","author":"Y Huang","year":"2003","unstructured":"Huang Y, Kowalski D . WEB-THERMODYN: sequence analysis software for profiling DNA helical stability. Nucleic Acids Res 2003; 31: 3819\u20133821.","journal-title":"Nucleic Acids Res"},{"key":"BFgene200863_CR17","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/0092-8674(88)90090-6","volume":"53","author":"K Araki","year":"1988","unstructured":"Araki K, Maeda H, Wang J, Kitamura D, Watanabe T . Purification of a nuclear trans-acting factor involved in the regulated transcription of a human immunoglobulin heavy chain gene. Cell 1988; 53: 723\u2013730.","journal-title":"Cell"},{"key":"BFgene200863_CR18","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1128\/MCB.01168-07","volume":"28","author":"W Feng","year":"2008","unstructured":"Feng W, Huang J, Zhang J, Williams T . Identification and analysis of a conserved Tcfap2a intronic enhancer element required for expression in facial and limb bud mesenchyme. Mol Cell Biol 2008; 28: 315\u2013325.","journal-title":"Mol Cell Biol"},{"key":"BFgene200863_CR19","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.ydbio.2007.08.036","volume":"311","author":"D Adams","year":"2007","unstructured":"Adams D, Karolak M, Robertson E, Oxburgh L . Control of kidney, eye and limb expression of Bmp7 by an enhancer element highly conserved between species. Dev Biol 2007; 311: 679\u2013690.","journal-title":"Dev Biol"},{"key":"BFgene200863_CR20","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.bbrc.2007.02.076","volume":"336","author":"P Flodby","year":"2007","unstructured":"Flodby P, Zhou B, Ann KD, Kim KJ, Minoo P, Cranddall ED et al. Conserved elements within first intron of aquaporin 5 (Aqp5) function as trabscritptional enhancers. Biochem Biophys Res Commun 2007; 336: 26\u201331.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFgene200863_CR21","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1093\/hmg\/ddn130","volume":"17","author":"CS Weickert","year":"2008","unstructured":"Weickert CS, Miranda-Angulo AL, Wong J, Perlman WR, Ward SE, Radhakrishna V et al. Variants in the estrogen receptor alpha gene and its mRNA contribute to risk for schizophrenia. Hum Mol Genet 2008; 17: 2293\u20132309.","journal-title":"Hum Mol Genet"},{"key":"BFgene200863_CR22","doi-asserted-by":"publisher","first-page":"e115","DOI":"10.1371\/journal.pgen.0030115","volume":"3","author":"A Scuteri","year":"2007","unstructured":"Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007; 3: e115.","journal-title":"PLoS Genet"},{"key":"BFgene200863_CR23","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/j.gde.2005.09.004","volume":"15","author":"MD Adams","year":"2005","unstructured":"Adams MD . Conserved sequences and the evolution of gene regulatory signals. Curr Opin Genet Dev 2005; 15: 628\u2013633.","journal-title":"Curr Opin Genet Dev"},{"key":"BFgene200863_CR24","first-page":"453","volume":"13","author":"R Gordan","year":"2008","unstructured":"Gordan R, Hartemink AJ . Using DNA duplex stability information for transcription factor binding site discovery. Pac Symp Biocomput 2008; 13: 453\u2013464.","journal-title":"Pac Symp Biocomput"},{"issue":"Suppl 1","key":"BFgene200863_CR25","doi-asserted-by":"publisher","first-page":"S126","DOI":"10.1186\/1753-6561-1-s1-s126","volume":"1","author":"W Liu-Mares","year":"2007","unstructured":"Liu-Mares W, Sun Z, Bamlet WR, Atkinson EJ, Fridley BL, Slager SL et al. Analysis of variation in NF-kappaB genes and expression levels of NF-kappaB-regulated molecules. BMC Proc 2007; 1 (Suppl 1): S126.","journal-title":"BMC Proc"},{"key":"BFgene200863_CR26","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/0167-5699(93)90182-K","volume":"14","author":"JD Mountz","year":"1993","unstructured":"Mountz JD, Talal N . Retroviruses, apoptosis and autogenes. Immun Today 1993; 14: 532\u2013536.","journal-title":"Immun Today"},{"key":"BFgene200863_CR27","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1146\/annurev.immunol.24.021605.090513","volume":"24","author":"N Bidere","year":"2006","unstructured":"Bidere N, Su HC, Lenardo MJ . Genetic disorders of programmed cell death in the immune system. Annu Rev Immunol 2006; 24: 321\u2013352.","journal-title":"Annu Rev Immunol"},{"key":"BFgene200863_CR28","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1002\/cncr.20270","volume":"100","author":"R Kim","year":"2004","unstructured":"Kim R, Emi M, Tanabe K, Uchida Y, Toge T . The role of Fas ligand and transforming growth factor beta in tumor progression: molecular mechanisms of immune privilege via Fas-mediated apoptosis and potential targets for cancer therapy. Cancer 2004; 100: 2281\u20132291.","journal-title":"Cancer"},{"key":"BFgene200863_CR29","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1093\/rheumatology\/kei113","volume":"45","author":"SL Peng","year":"2006","unstructured":"Peng SL . FAS(CD95)-related apoptosis and rheumatroid arthritis. Rheumatology 2006; 45: 26\u201330.","journal-title":"Rheumatology"},{"key":"BFgene200863_CR30","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1177\/1352458506070826","volume":"12","author":"L Lopatinskaya","year":"2006","unstructured":"Lopatinskaya L, Zwemmer J, Uitdehaag B, Lucas K, Polman C, Nagelkerken L . Mediators of apoptosis Fas and FasL predict disability progression in multiple sclerosis over a period of 10 years. Mult Scler 2006; 12: 704\u2013709.","journal-title":"Mult Scler"},{"key":"BFgene200863_CR31","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1046\/j.1469-0691.2003.00669.x","volume":"9","author":"DH Dockrell","year":"2003","unstructured":"Dockrell DH . The multiple roles of Fas ligand in the pathogenesis of infectious diseases. Clin Microbiol Infect 2003; 9: 766\u2013779.","journal-title":"Clin Microbiol Infect"},{"key":"BFgene200863_CR32","first-page":"97","volume":"28","author":"PI Hsu","year":"2008","unstructured":"Hsu PI, Lu PJ, Wang EM, Ger LP, Lo GH, Tsay FW et al. Polymorphisms of death pathway genes FAS and FASL and risk of premalignant gastric lesions. Anticancer Res 2008; 28: 97\u2013103.","journal-title":"Anticancer Res"},{"key":"BFgene200863_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00439-002-0839-7","volume":"112","author":"F Mekus","year":"2003","unstructured":"Mekus F, Laabs U, Veeze H, T\u00fcmmler B . Genes in the vicinity of CFTR modulate the cystic fibrosis phenotype in highly concordant or discordant F508del homozygous sib pairs. Hum Genet 2003; 112: 1\u201311.","journal-title":"Hum Genet"},{"key":"BFgene200863_CR34","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1038\/sj.ejhg.5201825","volume":"15","author":"T Becker","year":"2007","unstructured":"Becker T, Jansen S, Tamm S, Wienker TF, T\u00fcmmler B, Stanke F . Transmission ratio distortion and maternal effects confound the analysis of modulators of cystic fibrosis disease severity on 19q13. Eur J Hum Genet 2007; 15: 774\u2013778.","journal-title":"Eur J Hum Genet"},{"key":"BFgene200863_CR35","doi-asserted-by":"publisher","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","volume":"23","author":"MA Larkin","year":"2007","unstructured":"Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H et al. Clustal W and Clustal X version 2.0. Bioinformatics 2007; 23: 2947\u20132948.","journal-title":"Bioinformatics"},{"key":"BFgene200863_CR36","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1093\/bioinformatics\/btg430","volume":"20","author":"M Clamp","year":"2004","unstructured":"Clamp M, Cuff J, Searle SM, Barton GJ . The Jalview Java alignment editor. Bioinformatics 2004; 20: 426\u2013427.","journal-title":"Bioinformatics"},{"issue":"Web Server issu","key":"BFgene200863_CR37","doi-asserted-by":"publisher","first-page":"W432","DOI":"10.1093\/nar\/gki441","volume":"33","author":"DS Chekmenev","year":"2005","unstructured":"Chekmenev DS, Haid C, Kel AE . P-Match: transcription factor binding site search by combining patterns and weight matrices. Nucleic Acids Res 2005; 33 (Web Server issue): W432\u2013W437.","journal-title":"Nucleic Acids Res"},{"key":"BFgene200863_CR38","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1159\/000073727","volume":"56","author":"M Knapp","year":"2003","unstructured":"Knapp M, Becker T . Family-based association analysis with tightly linked markers. Hum Hered 2003; 56: 2\u20139.","journal-title":"Hum Hered"},{"key":"BFgene200863_CR39","first-page":"506","volume":"52","author":"RS Spielman","year":"1993","unstructured":"Spielman RS, McGinnis RE, Ewens WJ . Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993; 52: 506\u2013516.","journal-title":"Am J Hum Genet"},{"key":"BFgene200863_CR40","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1093\/bioinformatics\/16.2.182","volume":"16","author":"GR Abecasis","year":"2000","unstructured":"Abecasis GR, Cookson WO . GOLD-graphical overview of linkage disequilibrium. Bioinformatics 2000; 16: 182\u2013183.","journal-title":"Bioinformatics"}],"container-title":["Genes &amp; Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/gene200863.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gene200863","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gene200863.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T16:09:39Z","timestamp":1647965379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/gene200863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,7]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["BFgene200863"],"URL":"https:\/\/doi.org\/10.1038\/gene.2008.63","relation":{},"ISSN":["1466-4879","1476-5470"],"issn-type":[{"value":"1466-4879","type":"print"},{"value":"1476-5470","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8,7]]},"assertion":[{"value":"26 June 2008","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2008","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2008","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2008","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}