{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:41:02Z","timestamp":1791189662608,"version":"4.1.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2015,2,11]],"date-time":"2015-02-11T00:00:00Z","timestamp":1423612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"DOI":"10.1371\/journal.pgen.1004955","type":"journal-article","created":{"date-parts":[[2015,2,11]],"date-time":"2015-02-11T13:51:49Z","timestamp":1423662709000},"page":"e1004955","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":58,"title":["Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes"],"prefix":"10.1371","volume":"11","author":[{"given":"Natalie J.","family":"Prescott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Lehne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstin","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efterpi","family":"Papouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muddassar M.","family":"Mirza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Spain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Fraternali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzannah J.","family":"Bumpstead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariella","family":"Amar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Bye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Chung-Faye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bu\u2019Hussain","family":"Hayee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Pollok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Satsangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles","family":"Parkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Mansfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Sanderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathryn M.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Weale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Schlitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"UK IBD Genetics Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,2,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1053\/j.gastro.2011.10.001","article-title":"Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review","volume":"142","author":"NA Molodecky","year":"2012","journal-title":"Gastroenterology"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1056\/NEJMra020831","article-title":"Inflammatory bowel disease","volume":"347","author":"DK Podolsky","year":"2002","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nature10209","article-title":"Genetics and pathogenesis of inflammatory bowel disease","volume":"474","author":"B Khor","year":"2011","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nature11582","article-title":"Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease","volume":"491","author":"L Jostins","year":"2012","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/ng.f.136","article-title":"Common and rare variants in multifactorial susceptibility to common diseases","volume":"40","author":"W Bodmer","year":"2008","journal-title":"Nat Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/nature08494","article-title":"Finding the missing heritability of complex diseases","volume":"461","author":"TA Manolio","year":"2009","journal-title":"Nature"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/35079107","article-title":"Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn\u2019s disease","volume":"411","author":"JP Hugot","year":"2001","journal-title":"Nature"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/35079114","article-title":"A frameshift mutation in NOD2 associated with susceptibility to Crohn\u2019s disease","volume":"411","author":"Y Ogura","year":"2001","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1016\/S0140-6736(00)05063-7","article-title":"Association between insertion mutation in NOD2 gene and Crohn\u2019s disease in German and British populations","volume":"357","author":"J Hampe","year":"2001","journal-title":"Lancet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/ng.733","article-title":"Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease","volume":"43","author":"Y Momozawa","year":"2011","journal-title":"Nat Genet"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/ng.952","article-title":"Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease","volume":"43","author":"MA Rivas","year":"2011","journal-title":"Nat Genet"},{"key":"ref12","article-title":"Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis","author":"M Beaudoin","year":"2013","journal-title":"PLoS Genet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature12170","article-title":"Negligible impact of rare autoimmune-locus coding-region variants on missing heritability","volume":"498","author":"KA Hunt","year":"2013","journal-title":"Nature"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature05911","article-title":"Genome-wide Association Studies of 14,000 cases of Seven Common Human Diseases and 3,000 shared controls","volume":"447","year":"2007","journal-title":"Nature"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/gepi.20379","article-title":"A critical evaluation of genomic control methods for genetic association studies","volume":"33","author":"T Dadd","year":"2009","journal-title":"Genet Epidemiol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1093\/bioinformatics\/bts553","article-title":"Extra-binomial variation approach for analysis of pooled DNA sequencing data","volume":"28","author":"X Yang","year":"2012","journal-title":"Bioinformatics"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/humu.20264","article-title":"Mutation, selection, and evolution of the Crohn disease susceptibility gene CARD15","volume":"27","author":"K King","year":"2006","journal-title":"Hum Mutat"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"IA Adzhubei","year":"2010","journal-title":"Nat Methods"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm","volume":"4","author":"P Kumar","year":"2009","journal-title":"Nat Protoc"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/bioinformatics\/btt691","article-title":"mCSM: predicting the effects of mutations in proteins using graph-based signatures","volume":"30","author":"DE Pires","year":"2014","journal-title":"Bioinformatics"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.1093\/emboj\/19.14.3530","article-title":"Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12","volume":"19","author":"C Yoon","year":"2000","journal-title":"EMBO J"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.it.2011.09.007","article-title":"Butyrophilins: an emerging family of immune regulators","volume":"33","author":"L Abeler-Dorner","year":"2012","journal-title":"Trends Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.4049\/jimmunol.178.3.1523","article-title":"BTNL2, a butyrophilin\/B7-like molecule, is a negative costimulatory molecule modulated in intestinal inflammation","volume":"178","author":"HA Arnett","year":"2007","journal-title":"J Immunol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.4049\/jimmunol.1201760","article-title":"Butyrophilin-like 2 modulates B7 costimulation to induce Foxp3 expression and regulatory T cell development in mature T cells","volume":"190","author":"RM Swanson","year":"2013","journal-title":"J Immunol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/j.1399-0039.2009.01314.x","article-title":"Confirmation of the novel association at the BTNL2 locus with ulcerative colitis","volume":"74","author":"S Pathan","year":"2009","journal-title":"Tissue Antigens"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e43907","DOI":"10.1371\/journal.pone.0043907","article-title":"Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility","volume":"7","author":"I Adrianto","year":"2012","journal-title":"PLoS One"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/ng1519","article-title":"Sarcoidosis is associated with a truncating splice site mutation in BTNL2","volume":"37","author":"R Valentonyte","year":"2005","journal-title":"Nat Genet"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/jhg.2013.2","article-title":"Exome sequencing identifies novel rheumatoid arthritis-susceptible variants in the BTNL2","volume":"58","author":"S Mitsunaga","year":"2013","journal-title":"J Hum Genet"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1089\/cmb.1997.4.311","article-title":"Improved splice site detection in Genie","volume":"4","author":"MG Reese","year":"1997","journal-title":"J Comput Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"5240","DOI":"10.1046\/j.1432-1033.2002.03232.x","article-title":"Cloning and characterization of the mammalian-specific nicolin 1 gene (NICN1) encoding a nuclear 24 kDa protein","volume":"269","author":"B Backofen","year":"2002","journal-title":"Eur J Biochem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1126\/science.1167728","article-title":"Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes","volume":"324","author":"S Nejentsev","year":"2009","journal-title":"Science"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/ng.628","article-title":"Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia","volume":"42","author":"CT Johansen","year":"2010","journal-title":"Nat Genet"},{"key":"ref33","first-page":"369","article-title":"Genetic variation and activity of mouse Nod2, a susceptibility gene for Crohn\u2019s disease","volume":"81","author":"Y Ogura","year":"2003","journal-title":"Genomics"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/ng.2303","article-title":"Exome sequencing and the genetic basis of complex traits","volume":"44","author":"A Kiezun","year":"2012","journal-title":"Nat Genet"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"D32","DOI":"10.1093\/nar\/gkn721","article-title":"NCBI Reference Sequences: current status, policy and new initiatives","volume":"37","author":"KD Pruitt","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"D800","DOI":"10.1093\/nar\/gkq1064","article-title":"Ensembl 2011","volume":"39","author":"P Flicek","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1053\/j.gastro.2007.03.034","article-title":"A Nonsynonymous SNP in ATG16L1 Predisposes to Ileal Crohn\u2019s Disease and Is Independent of CARD15 and IBD5","volume":"132","author":"NJ Prescott","year":"2007","journal-title":"Gastroenterology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1093\/ije\/dyi183","article-title":"Cohort profile: 1958 British birth cohort (National Child Development Study)","volume":"35","author":"C Power","year":"2006","journal-title":"Int J Epidemiol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref40","unstructured":"Wysoker A, Tibbetts K, Fennell T, and Weisburd B, Picard Tools, 2009."},{"key":"ref41","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"K Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses","volume":"81","author":"S Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/gepi.10252","article-title":"Pedigree disequilibrium tests for multilocus haplotypes","volume":"25","author":"F Dudbridge","year":"2003","journal-title":"Genet Epidemiol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"HM Berman","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1006\/jmbi.2000.4042","article-title":"T-Coffee: A novel method for fast and accurate multiple sequence alignment","volume":"302","author":"C Notredame","year":"2000","journal-title":"J Mol Biol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-1-60327-058-8_8","article-title":"Protein structure modeling with MODELLER","volume":"426","author":"N Eswar","year":"2008","journal-title":"Methods Mol Biol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature05911","article-title":"Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls","volume":"447","year":"2007","journal-title":"Nature"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1005172","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T00:00:00Z","timestamp":1429228800000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pgen.1004955","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T17:21:36Z","timestamp":1566321696000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1004955"}},"subtitle":[],"editor":[{"given":"Mark I.","family":"McCarthy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,2,11]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,2,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1004955","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pgen.1005172","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,11]]}}}