{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:59:49Z","timestamp":1789639189768,"version":"4.0.0"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T00:00:00Z","timestamp":1600560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI125581, AI100627"],"award-info":[{"award-number":["AI125581, AI100627"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007423","name":"Lyda Hill Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We screened mice carrying homozygous and heterozygous <jats:italic>N<\/jats:italic>\u2010ethyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (ENU)\u2013induced germline mutations for aberrant antigen\u2010specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain\u2010specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B\u2010cell receptor signaling. The precise roles of the five remaining genes (<jats:italic>Flcn, Map1<\/jats:italic><jats:italic>lc3b, Me2<\/jats:italic>, <jats:italic>Prkd2,<\/jats:italic> and <jats:italic>Scarb2<\/jats:italic>) remain to be determined. Loss\u2010of\u2010function mutations in nine of the 12 genes limiting the IgE response were dominant or semi\u2010dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.14564","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T09:54:41Z","timestamp":1598608481000},"page":"1095-1108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Dominant atopy risk mutations identified by mouse forward genetic analysis"],"prefix":"10.1111","volume":"76","author":[{"given":"Jeffrey A.","family":"SoRelle","sequence":"first","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"},{"name":"Department of Pathology University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yue","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Huk","family":"Choi","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"},{"name":"Department of Immunology University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan\u2010wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhong","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Russell","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Scott","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darui","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Zhan","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Hui","family":"Bu","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"},{"name":"Department of Population and Data Sciences Quantitative Biomedical Research Center University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihwa","family":"Choi","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Tang","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Zhan","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Li","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Marie Y.","family":"Moresco","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3639-246X","authenticated-orcid":false,"given":"Bruce","family":"Beutler","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,20]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"21","article-title":"Molecular mechanisms of IgE class switch recombination","volume":"388","author":"Tong P","year":"2015","journal-title":"Curr Top Microbiol 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