{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:45:18Z","timestamp":1790401518970,"version":"4.1.0"},"reference-count":90,"publisher":"National Academy of Sciences","issue":"24","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-IAHU-01"],"award-info":[{"award-number":["ANR-10-IAHU-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Christian Dior Couture, Dior","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["Equipe FRM EQU201903007798"],"award-info":[{"award-number":["Equipe FRM EQU201903007798"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002350","name":"St. Giles Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002350","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012007","name":"Rockefeller University","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100012007","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10- LABX-62-IBEID"],"award-info":[{"award-number":["ANR-10- LABX-62-IBEID"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-LABX-69-22701"],"award-info":[{"award-number":["ANR-10-LABX-69-22701"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["Equipe FRM DEQ20180339214"],"award-info":[{"award-number":["Equipe FRM DEQ20180339214"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Qiagen Inc","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,6,16]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Human genes homozygous for apparent loss of function (LoF) variants are increasingly reported in a sizeable proportion of individuals without overt clinical phenotypes. Here, we found 166 genes with 179 predicted LoF variants for which the frequency of homozygous individuals exceeds 1% in at least one of the populations present in databases ExAC and gnomAD. These putatively dispensable genes showed relaxation of selective constraints, suggesting that a considerable proportion of these genes may be undergoing pseudogenization. Eight of these LoF variants displayed robust signals of positive selection, including two variants in genes involved in resistance to infectious diseases. The identification of dispensable genes will facilitate the identification of functions that are now redundant, or possibly even advantageous, for human survival.<\/jats:p>","DOI":"10.1073\/pnas.1917993117","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T16:07:04Z","timestamp":1591114024000},"page":"13626-13636","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["Common homozygosity for predicted loss-of-function variants reveals both redundant and advantageous effects of dispensable human genes"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4832-6101","authenticated-orcid":false,"given":"Antonio","family":"Rausell","sequence":"first","affiliation":[{"name":"Clinical Bioinformatics Laboratory, INSERM UMR1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Luo","sequence":"additional","affiliation":[{"name":"Clinical Bioinformatics Laboratory, INSERM UMR1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Lopez","sequence":"additional","affiliation":[{"name":"Human Evolutionary Genetics Unit, Institut Pasteur, UMR2000, CNRS, Paris 75015, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoann","family":"Seeleuthner","sequence":"additional","affiliation":[{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"},{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Necker Hospital for Sick Children, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Rapaport","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Favier","sequence":"additional","affiliation":[{"name":"Clinical Bioinformatics Laboratory, INSERM UMR1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Stenson","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, School of Medicine, Cardiff University, CF14 4XN Cardiff, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8943-8484","authenticated-orcid":false,"given":"David N.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, School of Medicine, Cardiff University, CF14 4XN Cardiff, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9911-4459","authenticated-orcid":false,"given":"Etienne","family":"Patin","sequence":"additional","affiliation":[{"name":"Human Evolutionary Genetics Unit, Institut Pasteur, UMR2000, CNRS, Paris 75015, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Laurent","family":"Casanova","sequence":"additional","affiliation":[{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"},{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065;"},{"name":"Howard Hughes Medical Institute, New York, NY 10065;"},{"name":"Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2429-6320","authenticated-orcid":false,"given":"Lluis","family":"Quintana-Murci","sequence":"additional","affiliation":[{"name":"Human Evolutionary Genetics Unit, Institut Pasteur, UMR2000, CNRS, Paris 75015, France;"},{"name":"Human Genomics and Evolution, Coll\u00e8ge de France, Paris 75005, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Abel","sequence":"additional","affiliation":[{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"},{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2014.11.003"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2016.02.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2017.12.008"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18714"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003757"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1464793106007068"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1779-6"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-017-0464-9"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-019-00737-x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1215040"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004494"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3243"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac8624"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature22034"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/40618"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/302219"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2698"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3421"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197608052950602"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0695-224"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/382722a0"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80110-5"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5283.1856"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm860"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.24.15351-15355.2005"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baw093"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1058"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1534\/g3.114.015784"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.1.308"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1120"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380040103"},{"key":"e_1_3_3_33_2","unstructured":"McKusick-Nathans Institute of Genetic Medicine Johns Hopkins University Online Mendelian Inheritance in Man OMIM. https:\/\/omim.org\/. Accessed 6 October 2019."},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2017.75"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1291872"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1222"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.594"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.227"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518646112"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msg013"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ympev.2012.07.032"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.007"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101335"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000562"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-017-0034-1"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21347"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003709"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.11.014"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002806"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1001025"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2611"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040072"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233321"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.800755"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111680"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep36468"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu633"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2015.2002"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01461"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23978-z"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004030"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2480"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msn049"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.009"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040052"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2010.0004"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt335"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0901053"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12293"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky587"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq248"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3786"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2006.07.009"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.09.010"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msp108"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193032"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfw451"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1098"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn828"},{"key":"e_1_3_3_81_2","unstructured":"K. J. Karczewski . Variation across 141 456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes. bioArxiv:10.1101\/531210 (30 January 2019)."},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(98)01208-0"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp215"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3664"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.01.062"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1013"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.06.009"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1917993117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1917993117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T05:32:07Z","timestamp":1649827927000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1917993117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,2]]},"references-count":90,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2020,6,16]]}},"alternative-id":["10.1073\/pnas.1917993117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1917993117","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/819615","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,2]]},"assertion":[{"value":"2020-06-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}