{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:10:31Z","timestamp":1789787431487,"version":"4.0.1"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"2","license":[{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M012212\/1"],"award-info":[{"award-number":["MR\/M012212\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","award":["PDF_003_20151124"],"award-info":[{"award-number":["PDF_003_20151124"]}],"id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Northern Counties Kidney Research UK","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100000098","name":"HHS | NIH | NIH Clinical Center","doi-asserted-by":"publisher","award":["DK1069274"],"award-info":[{"award-number":["DK1069274"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000098","name":"HHS | NIH | NIH Clinical Center","doi-asserted-by":"publisher","award":["DK1069274"],"award-info":[{"award-number":["DK1069274"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000098","name":"HHS | NIH | NIH Clinical Center","doi-asserted-by":"publisher","award":["DK064614"],"award-info":[{"award-number":["DK064614"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["DK064614"],"award-info":[{"award-number":["DK064614"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-A0-IAHU-01"],"award-info":[{"award-number":["ANR-A0-IAHU-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,1,14]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Our current understanding of genetic disease is often inadequate, largely due to genetic background effects that modify disease presentation. This is particularly challenging for rare diseases that lack sufficient numbers of patients for genome-wide association studies. We show in a series of experiments using a murine model of Joubert syndrome, a multisystem ciliopathy, that a single locus is a modifier of cystic kidney disease. We go on to show that the human homolog plays a similar role in disease using a cohort of patients. These findings make a significant contribution to the underplayed (and often ignored) role of genetic background in murine models and how this can be exploited to understand further rare inherited disease.<\/jats:p>","DOI":"10.1073\/pnas.1912602117","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T18:15:19Z","timestamp":1577384119000},"page":"1113-1118","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":31,"title":["Mouse genetics reveals Barttin as a genetic modifier of Joubert syndrome"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8531-1534","authenticated-orcid":false,"given":"Simon A.","family":"Ramsbottom","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne NE1 3BZ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E.","family":"Thelwall","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne NE1 3BZ, United Kingdom;"},{"name":"Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne NE4 5PL, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina M.","family":"Wood","sequence":"additional","affiliation":[{"name":"The Histopathology Department, The Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle upon Tyne NE7 7DN, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin J.","family":"Clowry","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Devlin","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne NE1 3BZ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Silbermann","sequence":"additional","affiliation":[{"name":"Laboratory of Hereditary Kidney Disease, Imagine Institute, INSERM U1163, Universit\u00e9 de Paris, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1039-5520","authenticated-orcid":false,"given":"Helena L.","family":"Spiewak","sequence":"additional","affiliation":[{"name":"Northern Genetics Service, International Centre for Life, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 3BZ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirlee","family":"Shril","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Molinari","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne NE1 3BZ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedhelm","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meral","family":"Gunay-Aygun","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"},{"name":"Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287;"},{"name":"McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Saunier","sequence":"additional","affiliation":[{"name":"Laboratory of Hereditary Kidney Disease, Imagine Institute, INSERM U1163, Universit\u00e9 de Paris, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather J.","family":"Cordell","sequence":"additional","affiliation":[{"name":"Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-3782","authenticated-orcid":false,"given":"John A.","family":"Sayer","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne NE1 3BZ, United Kingdom;"},{"name":"Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom;"},{"name":"National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne NE4 5PL, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin G.","family":"Miles","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne NE1 3BZ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12501"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1400280205"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02983018"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9382"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1513\/pats.201103-025SD"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.284"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1099-5"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12836"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61399"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1786"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1805"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/507318"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/519494"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.97"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21337"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa5370"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.009340"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1322373111"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517732538"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv137"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2380"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv123"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.19.9.813"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1091505"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx347"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.06.045"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1809432115"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng752"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/35107099"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.108.1.e5"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.5414\/CN107687"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfy333"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2019.07.005"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00130.2012"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1912602117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1912602117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T05:33:42Z","timestamp":1649828022000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1912602117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,26]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,1,14]]}},"alternative-id":["10.1073\/pnas.1912602117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1912602117","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737136384.793569417","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.737136384.793570506","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,26]]},"assertion":[{"value":"2019-12-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}