{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T12:04:34Z","timestamp":1769947474808,"version":"3.49.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"D1","license":[{"start":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T00:00:00Z","timestamp":1479168000000},"content-version":"vor","delay-in-days":393,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>DIDA (DIgenic diseases DAtabase) is a novel database that provides for the first time detailed information on genes and associated genetic variants involved in digenic diseases, the simplest form of oligogenic inheritance. The database is accessible via http:\/\/dida.ibsquare.be and currently includes 213 digenic combinations involved in 44 different digenic diseases. These combinations are composed of 364 distinct variants, which are distributed over 136 distinct genes. The web interface provides browsing and search functionalities, as well as documentation and help pages, general database statistics and references to the original publications from which the data have been collected. The possibility to submit novel digenic data to DIDA is also provided. Creating this new repository was essential as current databases do not allow one to retrieve detailed records regarding digenic combinations. Genes, variants, diseases and digenic combinations in DIDA are annotated with manually curated information and information mined from other online resources. Next to providing a unique resource for the development of new analysis methods, DIDA gives clinical and molecular geneticists a tool to find the most comprehensive information on the digenic nature of their diseases of interest.<\/jats:p>","DOI":"10.1093\/nar\/gkv1068","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T12:16:26Z","timestamp":1445343386000},"page":"D900-D907","source":"Crossref","is-referenced-by-count":96,"title":["DIDA: A curated and annotated digenic diseases database"],"prefix":"10.1093","volume":"44","author":[{"given":"Andrea M.","family":"Gazzo","sequence":"first","affiliation":[{"name":"Interuniversity Institute of Bioinformatics in Brussels, Boulevard du Triomphe CP 263, 1050 Brussels, Belgium"},{"name":"MLG, D\u00e9partement d'Informatique, Universit\u00e9 Libre de Bruxelles, Boulevard du Triomphe, CP 212, 1050 Brussels, Belgium"},{"name":"Center for Medical Genetics, Reproduction and Genetics, Reproduction Genetics and Regenerative Medicine, Vrije Universiteit Brussel, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"}]},{"given":"Dorien","family":"Daneels","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Bioinformatics in Brussels, Boulevard du Triomphe CP 263, 1050 Brussels, Belgium"},{"name":"Center for Medical Genetics, Reproduction and Genetics, Reproduction Genetics and Regenerative Medicine, Vrije Universiteit Brussel, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"}]},{"given":"Elisa","family":"Cilia","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Bioinformatics in Brussels, Boulevard du Triomphe CP 263, 1050 Brussels, Belgium"},{"name":"MLG, D\u00e9partement d'Informatique, Universit\u00e9 Libre de Bruxelles, Boulevard du Triomphe, CP 212, 1050 Brussels, Belgium"}]},{"given":"Maryse","family":"Bonduelle","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Reproduction and Genetics, Reproduction Genetics and Regenerative Medicine, Vrije Universiteit Brussel, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"}]},{"given":"Marc","family":"Abramowicz","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Bioinformatics in Brussels, Boulevard du Triomphe CP 263, 1050 Brussels, Belgium"},{"name":"Center for Medical Genetics, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"}]},{"given":"Sonia","family":"Van\u00a0Dooren","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Bioinformatics in Brussels, Boulevard du Triomphe CP 263, 1050 Brussels, Belgium"},{"name":"Center for Medical Genetics, Reproduction and Genetics, Reproduction Genetics and Regenerative Medicine, Vrije Universiteit Brussel, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"}]},{"given":"Guillaume","family":"Smits","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Bioinformatics in Brussels, Boulevard du Triomphe CP 263, 1050 Brussels, Belgium"},{"name":"Center for Medical Genetics, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"},{"name":"Genetics, H\u00f4pital Universitaire des Enfants Reine Fabiola, Universit\u00e9 Libre de Bruxelles, Avenue JJ Crocq 15, 1020 Brussels, Belgium"}]},{"given":"Tom","family":"Lenaerts","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Bioinformatics in Brussels, Boulevard du Triomphe CP 263, 1050 Brussels, Belgium"},{"name":"MLG, D\u00e9partement d'Informatique, Universit\u00e9 Libre de Bruxelles, Boulevard du Triomphe, CP 212, 1050 Brussels, Belgium"},{"name":"AI lab, Vakgroep Computerwetenschappen, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium"}]}],"member":"286","published-online":{"date-parts":[[2015,10,19]]},"reference":[{"key":"2021041108135811000_B1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/ejhg.2011.258","article-title":"Disease gene identification strategies for exome sequencing","volume":"20","author":"Gilissen","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"2021041108135811000_B2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/gm359","article-title":"Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress","volume":"4","author":"Lyon","year":"2012","journal-title":"Genome Med"},{"key":"2021041108135811000_B3","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nature13127","article-title":"Guidelines for investigating causality of sequence variants in human disease","volume":"508","author":"MacArthur","year":"2014","journal-title":"Nature"},{"key":"2021041108135811000_B4","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ajhg.2015.06.009","article-title":"The genetic basis of Mendelian phenotypes: discoveries, challenges, and opportunities","volume":"97","author":"Chong","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"2021041108135811000_B5","doi-asserted-by":"crossref","first-page":"D789","DOI":"10.1093\/nar\/gku1205","article-title":"OMIM.org: Online Mendelian Inheritance in Man (OMIM\u00ae), an online catalog of human genes and genetic disorders","volume":"43","author":"Amberger","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B6","doi-asserted-by":"crossref","first-page":"D6","DOI":"10.1093\/nar\/gku1130","article-title":"Database resources of the national center for biotechnology information","volume":"43","author":"NCBI, Resource Coordinators","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B7","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/humu.21438","article-title":"LOVD v.2.0: the next generation in gene variant databases","volume":"32","author":"Fokkema","year":"2011","journal-title":"Hum. Mutat."},{"key":"2021041108135811000_B8","doi-asserted-by":"crossref","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","article-title":"ClinVar: public archive of relationships among sequence variation and human phenotype","volume":"42","author":"Landrum","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B9","doi-asserted-by":"crossref","first-page":"D993","DOI":"10.1093\/nar\/gkt937","article-title":"DECIPHER: database for the interpretation of phenotype-linked plausibly pathogenic sequence and copy-number variation","volume":"42","author":"Bragin","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00439-013-1358-4","article-title":"The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine","volume":"133","author":"Stenson","year":"2014","journal-title":"Hum. Genet."},{"key":"2021041108135811000_B11","doi-asserted-by":"crossref","first-page":"R27","DOI":"10.1093\/hmg\/ddt384","article-title":"Databases of genomic variation and phenotypes: existing resources and future needs","volume":"22","author":"Johnston","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"2021041108135811000_B12","volume-title":"Vogel and Motulsky's Human Genetics: Problems and Approaches","author":"Vogel","year":"2010"},{"key":"2021041108135811000_B13","doi-asserted-by":"crossref","first-page":"R65","DOI":"10.1093\/hmg\/ddh092","article-title":"The oligogenic properties of Bardet\u2013Biedl syndrome","volume":"13","author":"Katsanis","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"2021041108135811000_B14","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1399-0004.2006.00671.x","article-title":"Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome","volume":"70","author":"Millat","year":"2006","journal-title":"Clin. Genet."},{"key":"2021041108135811000_B15","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1172\/JCI29884","article-title":"Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism","volume":"117","author":"Pitteloud","year":"2007","journal-title":"J. Clin. Invest."},{"key":"2021041108135811000_B16","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/ejhg.2008.206","article-title":"Kallmann syndrome","volume":"17","author":"Dod\u00e9","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"2021041108135811000_B17","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00383-009-2402-2","article-title":"Genetic basis of Hirschsprung's disease","volume":"25","author":"Tam","year":"2009","journal-title":"Pediatr. Surg. Int."},{"key":"2021041108135811000_B18","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1016\/j.fertnstert.2011.09.046","article-title":"The prevalence of digenic mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome","volume":"96","author":"Quaynor","year":"2011","journal-title":"Fertil. Steril."},{"key":"2021041108135811000_B19","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/jmedgenet-2013-101713","article-title":"Digenic inheritance in medical genetics","volume":"50","author":"Sch\u00e4ffer","year":"2013","journal-title":"J. Med. Genet."},{"key":"2021041108135811000_B20","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/humu.22745","article-title":"Recessive inheritance of population-specific intronic LINE-1 insertion causes a rotor syndrome phenotype","volume":"36","author":"Kagawa","year":"2015","journal-title":"Hum. Mutat."},{"key":"2021041108135811000_B21","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.ajhg.2015.03.007","article-title":"Copy-number variation of the glucose transporter gene SLC2A3 and congenital heart defects in the 22q11.2 deletion syndrome","volume":"96","author":"Mlynarski","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"2021041108135811000_B22","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1038\/ng.2479","article-title":"Digenic inheritance and Mendelian disease","volume":"44","author":"Lupski","year":"2012","journal-title":"Nat. Genet."},{"key":"2021041108135811000_B23","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ajhg.2009.12.001","article-title":"Missense mutations in TCF8 cause late-onset Fuchs corneal dystrophy and interact with FCD4 on chromosome 9p","volume":"86","author":"Riazuddin","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"2021041108135811000_B24","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N","article-title":"Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion","volume":"15","author":"den\u00a0Dunnen","year":"2000","journal-title":"Hum. Mutat."},{"key":"2021041108135811000_B25","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.ajhg.2009.09.003","article-title":"Clinical diagnostics in human genetics with semantic similarity searches in ontologies","volume":"85","author":"K\u00f6hler","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"2021041108135811000_B26","doi-asserted-by":"crossref","first-page":"D966","DOI":"10.1093\/nar\/gkt1026","article-title":"The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data","volume":"42","author":"K\u00f6hler","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B27","volume-title":"The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines","author":"World Health Organization","year":"1992"},{"key":"2021041108135811000_B28"},{"key":"2021041108135811000_B29","doi-asserted-by":"crossref","first-page":"D1079","DOI":"10.1093\/nar\/gku1071","article-title":"Genenames.org: the HGNC resources in 2015","volume":"43","author":"Gray","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B30","doi-asserted-by":"crossref","first-page":"D199","DOI":"10.1093\/nar\/gkt1076","article-title":"Data, information, knowledge and principle: back to metabolism in KEGG","volume":"42","author":"Kanehisa","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B31","doi-asserted-by":"crossref","first-page":"D472","DOI":"10.1093\/nar\/gkt1102","article-title":"The Reactome pathway knowledgebase","volume":"42","author":"Croft","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B32","doi-asserted-by":"crossref","first-page":"D222","DOI":"10.1093\/nar\/gkt1223","article-title":"Pfam: the protein families database","volume":"42","author":"Finn","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B33","doi-asserted-by":"crossref","first-page":"D213","DOI":"10.1093\/nar\/gku1243","article-title":"The InterPro protein families database: the classification resource after 15 years","volume":"43","author":"Mitchell","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B34","doi-asserted-by":"crossref","first-page":"D190","DOI":"10.1093\/nar\/gkm895","article-title":"The universal protein resource (UniProt)","volume":"36","author":"UniProtConsortium","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B35","doi-asserted-by":"crossref","first-page":"D358","DOI":"10.1093\/nar\/gkt1115","article-title":"The MIntAct project\u2013IntAct as a common curation platform for 11 molecular interaction databases","volume":"42","author":"Orchard","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B36","doi-asserted-by":"crossref","first-page":"D816","DOI":"10.1093\/nar\/gks1158","article-title":"The BioGRID interaction database: 2013 update","volume":"41","author":"Chatr-Aryamontri","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B37","doi-asserted-by":"crossref","first-page":"D793","DOI":"10.1093\/nar\/gks1055","article-title":"The ConsensusPathDB interaction database: 2013 update","volume":"41","author":"Kamburov","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2021041108135811000_B38","doi-asserted-by":"crossref","first-page":"6062","DOI":"10.1073\/pnas.0400782101","article-title":"A gene atlas of the mouse and human protein-encoding transcriptomes","volume":"101","author":"Su","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021041108135811000_B39","doi-asserted-by":"crossref","first-page":"e1001154","DOI":"10.1371\/journal.pgen.1001154","article-title":"Characterising and predicting haploinsufficiency in the human genome","volume":"6","author":"Huang","year":"2010","journal-title":"PLoS Genet."},{"key":"2021041108135811000_B40","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.1215040","article-title":"A systematic survey of loss-of-function variants in human protein-coding genes","volume":"335","author":"MacArthur","year":"2012","journal-title":"Science"},{"key":"2021041108135811000_B41","doi-asserted-by":"crossref","first-page":"e1003484","DOI":"10.1371\/journal.pgen.1003484","article-title":"From mouse to human: evolutionary genomics analysis of human orthologs of essential genes","volume":"9","author":"Georgi","year":"2013","journal-title":"PLoS Genet."},{"key":"2021041108135811000_B42","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":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"2021041108135811000_B43","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":"Kumar","year":"2009","journal-title":"Nat. Protoc."},{"key":"2021041108135811000_B44","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature11632","article-title":"An integrated map of genetic variation from 1,092 human genomes","volume":"491","author":"1000 Genomes Project Consortium","year":"2012","journal-title":"Nature"},{"key":"2021041108135811000_B45","volume-title":"Exome Variant Server"},{"key":"2021041108135811000_B46","doi-asserted-by":"crossref","first-page":"E2393","DOI":"10.1002\/humu.22376","article-title":"dbNSFP v2.0: a database of human non-synonymous SNVs and their functional predictions and annotations","volume":"34","author":"Liu","year":"2013","journal-title":"Hum. Mutat."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/44\/D1\/D900\/37018985\/gkv1068.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/44\/D1\/D900\/37018985\/gkv1068.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,11]],"date-time":"2021-04-11T08:15:35Z","timestamp":1618128935000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/44\/D1\/D900\/2502599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,19]]},"references-count":46,"journal-issue":{"issue":"D1","published-online":{"date-parts":[[2015,10,19]]},"published-print":{"date-parts":[[2016,1,4]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkv1068","relation":{},"ISSN":["1362-4962","0305-1048"],"issn-type":[{"value":"1362-4962","type":"electronic"},{"value":"0305-1048","type":"print"}],"subject":[],"published-other":{"date-parts":[[2016,1,4]]},"published":{"date-parts":[[2015,10,19]]}}}