{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:25:16Z","timestamp":1789424716380,"version":"build-2803163510"},"reference-count":20,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,9,25]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>del22q11<\/jats:italic>\n                    syndrome is associated with a highly\n variable phenotype despite the uniformity of the chromosomal deletion\n that causes the disease in most patients.\n                    <jats:italic>Df1<\/jats:italic>\n                    \/+ mice,\n which model\n                    <jats:italic>del22q11<\/jats:italic>\n                    , present with reduced penetrance of\n cardiovascular defects similar to those seen in deleted patients but\n not with other\n                    <jats:italic>del22q11<\/jats:italic>\n                    -like findings. The reduced\n penetrance of cardiovascular defects is caused by the ability of mutant\n embryos to recover from a fourth pharyngeal arch artery growth\n abnormality that is fully penetrant in early embryos. Here we show that\n genetic background has a major effect on penetrance of cardiovascular\n defects by affecting this embryonic recovery process. This effect could\n not be explained by allelic variation at the haploid locus, and it is\n likely to be caused by genetic modifiers elsewhere in the genome. We\n also show that genetic factors control extension of the\n                    <jats:italic>Df1<\/jats:italic>\n                    \/+ phenotype to include thymic and parathyroid\n anomalies, establishing the\n                    <jats:italic>Df1<\/jats:italic>\n                    mouse as a model for the\n genetic analysis of three major features of human\n                    <jats:italic>del22q11<\/jats:italic>\n                    syndrome. We found that in\n                    <jats:italic>Df1<\/jats:italic>\n                    \/+ mice, as in human patients, expression of the\n heart and thymic phenotypes are essentially independent from each\n other, suggesting that they may be controlled by different genetic\n modifiers. These data provide a framework for our understanding of\n phenotypic variability in patients with\n                    <jats:italic>del22q11<\/jats:italic>\n                    syndrome and the tools for its genetic dissection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.201127298","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"11428-11431","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":93,"title":["Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge\/\n                    <i>del22q11<\/i>\n                    syndromes"],"prefix":"10.1073","volume":"98","author":[{"given":"Ilaria","family":"Taddei","sequence":"first","affiliation":[{"name":"Department of Pediatrics (Cardiology), Baylor College of Medicine,\r 1 Baylor Plaza, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masae","family":"Morishima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Cardiology), Baylor College of Medicine,\r 1 Baylor Plaza, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuong","family":"Huynh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Cardiology), Baylor College of Medicine,\r 1 Baylor Plaza, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Lindsay","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Cardiology), Baylor College of Medicine,\r 1 Baylor Plaza, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,9,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.16.2421"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/302343"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.4.489"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320570339"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.7.1157"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320560216"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.10.798"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/515508"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/43900"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14608"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5414"},{"key":"e_1_3_3_12_2","first-page":"23","volume-title":"Molecular 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Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.201127298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T06:54:58Z","timestamp":1649832898000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.201127298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,9,18]]},"references-count":20,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2001,9,25]]}},"alternative-id":["10.1073\/pnas.201127298"],"URL":"https:\/\/doi.org\/10.1073\/pnas.201127298","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,9,18]]},"assertion":[{"value":"2001-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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