{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T07:02:43Z","timestamp":1777100563564,"version":"3.51.4"},"reference-count":76,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T00:00:00Z","timestamp":1676246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inherited retinal diseases (IRDs) are a group of ocular conditions characterized by an elevated genetic and clinical heterogeneity. They are transmitted almost invariantly as monogenic traits. However, with more than 280 disease genes identified so far, association of clinical phenotypes with genotypes can be very challenging, and molecular diagnosis is essential for genetic counseling and correct management of the disease. In addition, the prevalence and the assortment of IRD mutations are often population-specific. In this work, we examined 230 families from Portugal, with individuals suffering from a variety of IRD diagnostic classes (270 subjects in total). Overall, we identified 157 unique mutations (34 previously unreported) in 57 distinct genes, with a diagnostic rate of 76%. The IRD mutational landscape was, to some extent, different from those reported in other European populations, including Spanish cohorts. For instance, the EYS gene appeared to be the most frequently mutated, with a prevalence of 10% among all IRD cases. This was, in part, due to the presence of a recurrent and seemingly founder mutation involving the deletion of exons 13 and 14 of this gene. Moreover, our analysis highlighted that as many as 51% of our cases had mutations in a homozygous state. To our knowledge, this is the first study assessing a cross-sectional genotype\u2013phenotype landscape of IRDs in Portugal. Our data reveal a rather unique distribution of mutations, possibly shaped by a small number of rare ancestral events that have now become prevalent alleles in patients.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgad043","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T18:09:23Z","timestamp":1676311763000},"source":"Crossref","is-referenced-by-count":44,"title":["The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8157-9568","authenticated-orcid":false,"given":"Virginie G","family":"Peter","sequence":"first","affiliation":[{"name":"Institute of Molecular and Clinical Ophthalmology Basel (IOB) , Basel 4031 , Switzerland"},{"name":"Department of Ophthalmology, University of Basel , Basel 4031 , Switzerland"},{"name":"Department of Ophthalmology, Inselspital, Bern University Hospital , Bern 3010 , Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4720-5527","authenticated-orcid":false,"given":"Karolina","family":"Kaminska","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Ophthalmology Basel (IOB) , Basel 4031 , Switzerland"},{"name":"Department of Ophthalmology, University of Basel , Basel 4031 , Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-2180","authenticated-orcid":false,"given":"Cristina","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Instituto de Oftalmologia Dr Gama Pinto (IOGP) , Lisbon 1169-019 , Portugal"},{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa , Lisbon 1169-056 , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9841-4433","authenticated-orcid":false,"given":"Mathieu","family":"Quinodoz","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Ophthalmology Basel (IOB) , Basel 4031 , Switzerland"},{"name":"Department of Ophthalmology, University of Basel , Basel 4031 , Switzerland"},{"name":"Department of Genetics and Genome Biology, University of Leicester , Leicester LE1 7RH , UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8476-5366","authenticated-orcid":false,"given":"Francesca","family":"Cancellieri","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Ophthalmology Basel (IOB) , Basel 4031 , Switzerland"},{"name":"Department of Ophthalmology, University of Basel , Basel 4031 , Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2711-0480","authenticated-orcid":false,"given":"Katarina","family":"Cisarova","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, University of Lausanne , Lausanne 1015 , Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2434-7530","authenticated-orcid":false,"given":"Rosanna","family":"Pescini Gobert","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, University of Lausanne , Lausanne 1015 , Switzerland"}]},{"given":"Raquel","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hospital Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte (CHULN) , Lisbon 1649-035 , Portugal"}]},{"given":"S\u00f3nia","family":"Cust\u00f3dio","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hospital Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte (CHULN) , Lisbon 1649-035 , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9312-9924","authenticated-orcid":false,"given":"Liliana P","family":"Paris","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Instituto de Oftalmologia Dr Gama Pinto (IOGP) , Lisbon 1169-019 , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5889-2492","authenticated-orcid":false,"given":"Ana Berta","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hospital Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte (CHULN) , Lisbon 1649-035 , Portugal"},{"name":"Laboratory of Basic Immunology, Faculty of Medicine, University of Lisbon , Lisbon 1649-028 , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6181-4505","authenticated-orcid":false,"given":"Luisa","family":"Coutinho Santos","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Instituto de Oftalmologia Dr Gama Pinto (IOGP) , Lisbon 1169-019 , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0733-9950","authenticated-orcid":false,"given":"Carlo","family":"Rivolta","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Ophthalmology Basel (IOB) , Basel 4031 , Switzerland"},{"name":"Department of Ophthalmology, University of Basel , Basel 4031 , Switzerland"},{"name":"Department of Genetics and Genome Biology, University of Leicester , Leicester LE1 7RH , UK"}]}],"member":"286","published-online":{"date-parts":[[2023,2,13]]},"reference":[{"key":"2023072621120332600_pgad043-B1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/gm155","article-title":"Retinitis pigmentosa and allied conditions today: a paradigm of translational research","volume":"2","author":"Ayuso","year":"2010","journal-title":"Genome Med"},{"key":"2023072621120332600_pgad043-B2","article-title":"Clinical characteristics and current therapies for inherited retinal degenerations","volume":"5","author":"Sahel","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2023072621120332600_pgad043-B3"},{"key":"2023072621120332600_pgad043-B4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1167\/tvst.7.4.6","article-title":"Inherited retinal degenerations: current landscape and knowledge gaps","volume":"7","author":"Duncan","year":"2018","journal-title":"Transl Vis Sci Technol"},{"key":"2023072621120332600_pgad043-B5","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/ajmg.c.31842","article-title":"The new landscape of retinal gene therapy","volume":"184","author":"Ku","year":"2020","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2023072621120332600_pgad043-B6","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1055\/a-1384-0818","article-title":"Gene therapy for inherited retinal disorders: update on clinical trials","volume":"238","author":"Michalakis","year":"2021","journal-title":"Klin Monbl Augenheilkd"},{"key":"2023072621120332600_pgad043-B7","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1016\/j.ophtha.2017.04.008","article-title":"Clinically focused molecular investigation of 1000 consecutive families with inherited retinal disease","volume":"124","author":"Stone","year":"2017","journal-title":"Ophthalmology"},{"key":"2023072621120332600_pgad043-B8","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1038\/s41598-021-81093-y","article-title":"Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications","volume":"11","author":"Perea-Romero","year":"2021","journal-title":"Sci Rep"},{"key":"2023072621120332600_pgad043-B9","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1186\/s13023-021-01841-1","article-title":"Target 5000: a standardized all-Ireland pathway for the diagnosis and management of inherited retinal degenerations","volume":"16","author":"Stephenson","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"2023072621120332600_pgad043-B10","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12920-021-00874-6","article-title":"Whole-exome sequencing in 168 Korean patients with inherited retinal degeneration","volume":"14","author":"Ma","year":"2021","journal-title":"BMC Med Genomics"},{"key":"2023072621120332600_pgad043-B11","first-page":"457","article-title":"Non-syndromic inherited retinal diseases in Poland: genes, mutations, and phenotypes","volume":"27","author":"Tracewska","year":"2021","journal-title":"Mol Vis"},{"key":"2023072621120332600_pgad043-B12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ajhg.2016.12.003","article-title":"Comprehensive rare variant analysis via whole-genome sequencing to determine the molecular pathology of inherited retinal disease","volume":"100","author":"Carss","year":"2017","journal-title":"Am J Hum Genet"},{"key":"2023072621120332600_pgad043-B13","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1136\/jmedgenet-2018-105691","article-title":"Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients","volume":"56","author":"Koyanagi","year":"2019","journal-title":"J Med Genet"},{"key":"2023072621120332600_pgad043-B14","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3390\/genes5010176","article-title":"The molecular basis of retinal dystrophies in Pakistan","volume":"5","author":"Khan","year":"2014","journal-title":"Genes (Basel)"},{"key":"2023072621120332600_pgad043-B15","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1002\/humu.24064","article-title":"Genetic architecture of inherited retinal degeneration in Germany: a large cohort study from a single diagnostic center over a 9-year period","volume":"41","author":"Weisschuh","year":"2020","journal-title":"Hum Mutat"},{"key":"2023072621120332600_pgad043-B16","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ydbio.2011.09.001","article-title":"Mutations in Traf3ip1 reveal defects in ciliogenesis, embryonic development, and altered cell size regulation","volume":"360","author":"Berbari","year":"2011","journal-title":"Dev Biol"},{"key":"2023072621120332600_pgad043-B17","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1002\/humu.23294","article-title":"Leveraging splice-affecting variant predictors and a minigene validation system to identify Mendelian disease-causing variants among exon-captured variants of uncertain significance","volume":"38","author":"Soens","year":"2017","journal-title":"Hum Mutat"},{"key":"2023072621120332600_pgad043-B18","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/ejhg.2017.9","article-title":"Diagnostic exome sequencing in 266 Dutch patients with visual impairment","volume":"25","author":"Haer-Wigman","year":"2017","journal-title":"Eur J Hum Genet"},{"key":"2023072621120332600_pgad043-B19","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/j.ophtha.2020.04.008","article-title":"Genetic basis of inherited retinal disease in a molecularly characterized cohort of more than 3000 families from the United Kingdom","volume":"127","author":"Pontikos","year":"2020","journal-title":"Ophthalmology"},{"key":"2023072621120332600_pgad043-B20","doi-asserted-by":"crossref","first-page":"643","DOI":"10.3390\/genes9120643","article-title":"Exploring the variable phenotypes of RPGR carrier females in assessing their potential for retinal gene therapy","volume":"9","author":"Nanda","year":"2018","journal-title":"Genes (Basel)"},{"key":"2023072621120332600_pgad043-B21","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.oret.2019.11.010","article-title":"X-chromosome inactivation is a biomarker of clinical severity in female carriers of RPGR-associated X-linked retinitis pigmentosa","volume":"4","author":"Fahim","year":"2020","journal-title":"Ophthalmol Retina"},{"key":"2023072621120332600_pgad043-B22","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1167\/tvst.11.1.6","article-title":"Prevalence of RPGR-mediated retinal dystrophy in an unselected cohort of over 5000 patients","volume":"11","author":"Tuupanen","year":"2022","journal-title":"Transl Vis Sci Technol"},{"key":"2023072621120332600_pgad043-B23","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3390\/ijms22010381","article-title":"Expanding the clinical and genetic spectrum of RAB28-related cone-rod dystrophy: pathogenicity of novel variants in Italian families","volume":"22","author":"Iarossi","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2023072621120332600_pgad043-B24","doi-asserted-by":"crossref","first-page":"7398","DOI":"10.3390\/ijms23137398","article-title":"The clinical spectrum and disease course of DRAM2 retinopathy","volume":"23","author":"Krasovec","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2023072621120332600_pgad043-B25","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.3390\/genes12111824","article-title":"The genetic landscape of inherited retinal diseases in a Mexican cohort: genes","volume":"12","author":"Villanueva-Mendoza","year":"2021","journal-title":"Mutations and Phenotypes. Genes (Basel)"},{"key":"2023072621120332600_pgad043-B26","doi-asserted-by":"crossref","first-page":"995","DOI":"10.3390\/ijms23020995","article-title":"Clinical and genetic re-evaluation of inherited retinal degeneration pedigrees following initial negative findings on panel-based next generation sequencing","volume":"23","author":"Stephenson","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2023072621120332600_pgad043-B27","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/0092-8674(95)90274-0","article-title":"Isolation of a novel gene underlying Batten disease, CLN3","volume":"82","author":"Consortium","year":"1995","journal-title":"Cell"},{"key":"2023072621120332600_pgad043-B28","doi-asserted-by":"crossref","first-page":"5625","DOI":"10.1167\/iovs.11-7292","article-title":"Copy-number variations in EYS: a significant event in the appearance of arRP","volume":"52","author":"Pieras","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2023072621120332600_pgad043-B29","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.ophtha.2019.03.018","article-title":"Genomic landscape of sporadic retinitis Pigmentosa: findings from 877 Spanish cases","volume":"126","author":"Martin-Merida","year":"2019","journal-title":"Ophthalmology"},{"key":"2023072621120332600_pgad043-B30","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1167\/iovs.62.2.13","article-title":"Molecular epidemiology in 591 Italian probands with nonsyndromic retinitis pigmentosa and usher syndrome","volume":"62","author":"Colombo","year":"2021","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2023072621120332600_pgad043-B31","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1007\/s00417-021-05411-w","article-title":"EYS-associated sector retinitis pigmentosa","volume":"260","author":"Marques","year":"2022","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"2023072621120332600_pgad043-B32","first-page":"584","article-title":"ABCA4 mutations in Portuguese stargardt patients: identification of new mutations and their phenotypic analysis","volume":"15","author":"Maia-Lopes","year":"2009","journal-title":"Mol Vis"},{"key":"2023072621120332600_pgad043-B33","doi-asserted-by":"crossref","first-page":"332","DOI":"10.20344\/amp.15802","article-title":"Inherited retinal degenerations in Portugal: addressing the unmet needs","volume":"34","author":"Marques","year":"2021","journal-title":"Acta Med Port"},{"key":"2023072621120332600_pgad043-B34","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/s13023-020-01591-6","article-title":"Design, development and deployment of a web-based interoperable registry for inherited retinal dystrophies in Portugal: the IRD-PT","volume":"15","author":"Marques","year":"2020","journal-title":"Orphanet J Rare Dis"},{"key":"2023072621120332600_pgad043-B35","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(17)31868-8","article-title":"Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial","volume":"390","author":"Russell","year":"2017","journal-title":"Lancet"},{"key":"2023072621120332600_pgad043-B36","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1008315","article-title":"Mutations in ARL2BP, a protein required for ciliary microtubule structure, cause syndromic male infertility in humans and mice","volume":"15","author":"Moye","year":"2019","journal-title":"PLoS Genet"},{"key":"2023072621120332600_pgad043-B37","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/humu.24150","article-title":"New clinical and molecular evidence linking mutations in ARSG to Usher syndrome type IV","volume":"42","author":"Peter","year":"2021","journal-title":"Hum Mutat"},{"key":"2023072621120332600_pgad043-B38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41525-021-00214-8","article-title":"Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD","volume":"6","author":"Sangermano","year":"2021","journal-title":"NPJ Genom Med"},{"key":"2023072621120332600_pgad043-B39","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1080\/13816810.2022.2103834","article-title":"Anisometropia and asymmetric ABCA4-related cone-rod dystrophy","volume":"43","author":"Santos","year":"2022","journal-title":"Ophthalmic Genet"},{"key":"2023072621120332600_pgad043-B40","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2023072621120332600_pgad043-B41"},{"key":"2023072621120332600_pgad043-B42","doi-asserted-by":"crossref","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"Gigascience"},{"key":"2023072621120332600_pgad043-B43","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res"},{"key":"2023072621120332600_pgad043-B44","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat Genet"},{"key":"2023072621120332600_pgad043-B45","doi-asserted-by":"crossref","first-page":"11.10.1","DOI":"10.1002\/0471250953.bi1110s43","article-title":"From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline","volume":"43","author":"Van der Auwera","year":"2013","journal-title":"Curr Protoc Bioinformatics"},{"key":"2023072621120332600_pgad043-B46","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2023072621120332600_pgad043-B47","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"2023072621120332600_pgad043-B48","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature11690","article-title":"Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants","volume":"493","author":"Fu","year":"2013","journal-title":"Nature"},{"key":"2023072621120332600_pgad043-B49","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/humu.23220","article-title":"Exomic variants of an elderly cohort of Brazilians in the ABraOM database","volume":"38","author":"Naslavsky","year":"2017","journal-title":"Hum Mutat"},{"key":"2023072621120332600_pgad043-B50","doi-asserted-by":"crossref","first-page":"8018","DOI":"10.1038\/ncomms9018","article-title":"Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals","volume":"6","author":"Nagasaki","year":"2015","journal-title":"Nat Commun"},{"key":"2023072621120332600_pgad043-B51","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/ng.3592","article-title":"Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery","volume":"48","author":"Scott","year":"2016","journal-title":"Nat Genet"},{"key":"2023072621120332600_pgad043-B52","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13073-020-00803-9","article-title":"dbNSFP v4: a comprehensive database of transcript-specific functional predictions and annotations for human nonsynonymous and splice-site SNVs","volume":"12","author":"Liu","year":"2020","journal-title":"Genome Med"},{"key":"2023072621120332600_pgad043-B53","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.ajhg.2022.01.006","article-title":"Analysis of missense variants in the human genome reveals widespread gene-specific clustering and improves prediction of pathogenicity","volume":"109","author":"Quinodoz","year":"2022","journal-title":"Am J Hum Genet"},{"key":"2023072621120332600_pgad043-B54","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<57::AID-HUMU12>3.0.CO;2-G","article-title":"Online Mendelian Inheritance in Man (OMIM)","volume":"15","author":"Hamosh","year":"2000","journal-title":"Hum Mutat"},{"key":"2023072621120332600_pgad043-B55","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-4939-7737-6_7","article-title":"Mouse genome informatics (MGI) is the international resource for information on the laboratory mouse","volume":"1757","author":"Law","year":"2018","journal-title":"Methods Mol Biol"},{"key":"2023072621120332600_pgad043-B56","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ajhg.2017.09.001","article-title":"DOMINO: using machine learning to predict genes associated with dominant disorders","volume":"101","author":"Quinodoz","year":"2017","journal-title":"Am J Hum Genet"},{"key":"2023072621120332600_pgad043-B57","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1089\/1066527041410418","article-title":"Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals","volume":"11","author":"Yeo","year":"2004","journal-title":"J Comput Biol"},{"key":"2023072621120332600_pgad043-B58","doi-asserted-by":"crossref","first-page":"13534","DOI":"10.1093\/nar\/gku1206","article-title":"In silico prediction of splice-altering single nucleotide variants in the human genome","volume":"42","author":"Jian","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023072621120332600_pgad043-B59","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2018.12.015","article-title":"Predicting splicing from primary sequence with deep learning","volume":"176","author":"Jaganathan","year":"2019","journal-title":"Cell"},{"key":"2023072621120332600_pgad043-B60","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s41436-020-0749-x","article-title":"Mobile element insertion detection in 89,874 clinical exomes","volume":"22","author":"Torene","year":"2020","journal-title":"Genet Med"},{"key":"2023072621120332600_pgad043-B61","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1101\/gr.218032.116","article-title":"The Mobile Element Locator Tool (MELT): population-scale mobile element discovery and biology","volume":"27","author":"Gardner","year":"2017","journal-title":"Genome Res"},{"key":"2023072621120332600_pgad043-B62","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1093\/bioinformatics\/bts526","article-title":"A robust model for read count data in exome sequencing experiments and implications for copy number variant calling","volume":"28","author":"Plagnol","year":"2012","journal-title":"Bioinformatics"},{"key":"2023072621120332600_pgad043-B63","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1093\/bioinformatics\/btx699","article-title":"Mosdepth: quick coverage calculation for genomes and exomes","volume":"34","author":"Pedersen","year":"2018","journal-title":"Bioinformatics"},{"key":"2023072621120332600_pgad043-B64"},{"key":"2023072621120332600_pgad043-B65","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1101\/gr.6861907","article-title":"PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data","volume":"17","author":"Wang","year":"2007","journal-title":"Genome Res"},{"key":"2023072621120332600_pgad043-B66","doi-asserted-by":"crossref","first-page":"e138","DOI":"10.1093\/nar\/gkn641","article-title":"Modeling genetic inheritance of copy number variations","volume":"36","author":"Wang","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"2023072621120332600_pgad043-B67"},{"key":"2023072621120332600_pgad043-B68","doi-asserted-by":"crossref","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","article-title":"Clinvar: public archive of interpretations of clinically relevant variants","volume":"44","author":"Landrum","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023072621120332600_pgad043-B69","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"2023072621120332600_pgad043-B70","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1001025","article-title":"Identifying a high fraction of the human genome to be under selective constraint using GERP++","volume":"6","author":"Davydov","year":"2010","journal-title":"PLoS Comput Biol"},{"key":"2023072621120332600_pgad043-B71","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/humu.23348","article-title":"Variantvalidator: accurate validation, mapping, and formatting of sequence variation descriptions","volume":"39","author":"Freeman","year":"2018","journal-title":"Hum Mutat"},{"key":"2023072621120332600_pgad043-B72","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/humu.22981","article-title":"HGVS recommendations for the description of sequence variants: 2016 update","volume":"37","author":"den Dunnen","year":"2016","journal-title":"Hum Mutat"},{"key":"2023072621120332600_pgad043-B73","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"2023072621120332600_pgad043-B74","doi-asserted-by":"crossref","first-page":"W71","DOI":"10.1093\/nar\/gkm306","article-title":"Primer3Plus, an enhanced web interface to Primer3","volume":"35","author":"Untergasser","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2023072621120332600_pgad043-B75","doi-asserted-by":"crossref","DOI":"10.1093\/database\/bay119","article-title":"Ensembl variation resources","volume":"2018","author":"Hunt","year":"2018","journal-title":"Database (Oxford)"},{"key":"2023072621120332600_pgad043-B76","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/s41467-020-20584-4","article-title":"Automap is a high performance homozygosity mapping tool using next-generation sequencing data","volume":"12","author":"Quinodoz","year":"2021","journal-title":"Nat Commun"}],"container-title":["PNAS Nexus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pnasnexus\/advance-article-pdf\/doi\/10.1093\/pnasnexus\/pgad043\/49171360\/pgad043.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/2\/3\/pgad043\/50969447\/pgad043.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/2\/3\/pgad043\/50969447\/pgad043.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T21:27:44Z","timestamp":1690406864000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article\/doi\/10.1093\/pnasnexus\/pgad043\/7035493"}},"subtitle":[],"editor":[{"given":"Amalio","family":"Telenti","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2023,2,13]]},"references-count":76,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3,3]]}},"URL":"https:\/\/doi.org\/10.1093\/pnasnexus\/pgad043","relation":{},"ISSN":["2752-6542"],"issn-type":[{"value":"2752-6542","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,3,1]]},"published":{"date-parts":[[2023,2,13]]},"article-number":"pgad043"}}