{"entity": "journal", "iuid": "79b409bf19904674a0b1bb64d798b8dc", "timestamp": "2026-07-15T07:35:41.887Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Eur.%20J.%20Hum.%20Genet..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Eur.%20J.%20Hum.%20Genet."}}, "title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "issn-l": "1018-4813", "publications_count": 32, "publications": [{"entity": "publication", "iuid": "abaf1e9bf72441a4a14b06619ce812b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/abaf1e9bf72441a4a14b06619ce812b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/abaf1e9bf72441a4a14b06619ce812b3"}}, "title": "Genome sequencing in a cohort of 32 fetuses with genetic skeletal disorders.", "authors": [{"family": "Lindel\u00f6f", "given": "Hillevi", "initials": "H"}, {"family": "Hammarsj\u00f6", "given": "Anna", "initials": "A"}, {"family": "Voss", "given": "Ulrika", "initials": "U"}, {"family": "Gaetana Piticchio", "given": "Serena", "initials": "S"}, {"family": "Conner", "given": "Peter", "initials": "P"}, {"family": "Papadogiannakis", "given": "Nikos", "initials": "N"}, {"family": "Batkovskyte", "given": "Dominyka", "initials": "D", "orcid": "0000-0002-0492-1259", "researcher": {"href": "https://publications.scilifelab.se/researcher/017749b78ac540a6b2a36303130606f2.json"}}, {"family": "Orellana", "given": "Laura", "initials": "L", "orcid": "0000-0003-1927-555X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c614cf477d9044e28ae901600cc84e7d.json"}}, {"family": "Kvarnung", "given": "Malin", "initials": "M"}, {"family": "Malmgren", "given": "Helena", "initials": "H"}, {"family": "Lagerstedt Robinson", "given": "Kristina", "initials": "K"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Nishimura", "given": "Gen", "initials": "G"}, {"family": "Grigelioniene", "given": "Giedre", "initials": "G", "orcid": "0000-0001-9601-3137", "researcher": {"href": "https://publications.scilifelab.se/researcher/684864357acd490cb627f38fed3b82a4.json"}}], "type": "journal article", "published": "2025-11-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "33", "issue": "11", "pages": "1474-1483", "issn-l": "1018-4813"}, "abstract": "Approximately 200 genetic skeletal disorders can present prenatally, detectable through ultrasound abnormalities during pregnancy. Severe forms are typically identified during the first or second trimester, whereas milder phenotypes are recognized later, in the third trimester. Diagnosing skeletal dysplasia prenatally is challenging due to the large number of disorders and the overlapping clinical findings that can be detected by ultrasound. This study, conducted at Karolinska University Hospital between 2015 and 2022, examines the genetic and radiographic findings in 32 fetuses (14 female and 18 male, from unrelated families) with skeletal abnormalities detected on prenatal ultrasound and confirmed by radiographs at birth or after pregnancy termination. Fetal DNA samples from all 32 fetuses underwent singleton genome sequencing using an in silico skeletal dysplasia gene panel. As a second step, for six fetuses with molecularly unsolved diagnoses, trio genome sequencing analysis involving the fetus and both parents was performed. The diagnostic yield of genome sequencing was 72%, with pathogenic or likely pathogenic variants identified in 23 of the 32 fetuses. Additionally, four variants of uncertain significance, strongly suspected to be causative based on clinical and radiographic features, as well as structural protein analyses, were identified in four fetuses with autosomal recessive conditions. The diagnoses of five fetuses remain molecularly unsolved. In conclusion, by combining detailed phenotypic data with singleton genome sequencing we were able to reach a genetic diagnosis in 72% of 32 fetal genetic skeletal disorder cases investigated at the Karolinska University Hospital.", "doi": "10.1038/s41431-025-01886-x", "pmid": "40500351", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12583725"}, {"db": "pii", "key": "10.1038/s41431-025-01886-x"}], "notes": [], "created": "2025-11-18T20:45:58.654Z", "modified": "2025-11-28T18:04:38.525Z"}, {"entity": "publication", "iuid": "fc2e7d5d9c71484a92eb5a8c6ae44616", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fc2e7d5d9c71484a92eb5a8c6ae44616.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fc2e7d5d9c71484a92eb5a8c6ae44616"}}, "title": "UYSD: a novel data repository accessible via public website for worldwide population frequencies of Y-SNP haplogroups.", "authors": [{"family": "Ralf", "given": "Arwin", "initials": "A", "orcid": "0000-0001-6052-0807", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d150af894044707baff5f5e9b70b556.json"}}, {"family": "Zandstra", "given": "Dion", "initials": "D", "orcid": "0000-0002-2197-6315", "researcher": {"href": "https://publications.scilifelab.se/researcher/f58e22ae5aaf4049a605267f970f7334.json"}}, {"family": "van Wersch", "given": "Bram", "initials": "B"}, {"family": "K\u00f6ksal", "given": "Zehra", "initials": "Z", "orcid": "0000-0002-0914-9384", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb480dc4583d4dd893cc6d9efc1094ed.json"}}, {"family": "Larmuseau", "given": "Maarten H D", "initials": "MHD", "orcid": "0000-0002-5974-7235", "researcher": {"href": "https://publications.scilifelab.se/researcher/98a3deba601b4b31b0cda42fe888e30a.json"}}, {"family": "Rosa", "given": "Alexandra", "initials": "A"}, {"family": "Jobling", "given": "Mark A", "initials": "MA"}, {"family": "D'Amato", "given": "Maria E", "initials": "ME"}, {"family": "Courts", "given": "Cornelius", "initials": "C", "orcid": "0000-0002-9811-8482", "researcher": {"href": "https://publications.scilifelab.se/researcher/066aed6d98534e1b9a4a3cf860c13083.json"}}, {"family": "Gysi", "given": "Mario", "initials": "M"}, {"family": "Haas", "given": "Cordula", "initials": "C", "orcid": "0000-0001-8122-1427", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea35da82d5b143a89ace9e4a2aec1d64.json"}}, {"family": "Flores", "given": "Rodrigo", "initials": "R"}, {"family": "Neis", "given": "Maximilian", "initials": "M", "orcid": "0000-0002-8817-8668", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef17ea28f26d4e788df7d01737be765a.json"}}, {"family": "Wetton", "given": "Jon H", "initials": "JH", "orcid": "0000-0001-8337-4654", "researcher": {"href": "https://publications.scilifelab.se/researcher/877cefdb3bf04df6b0fb80b5f54a0f7a.json"}}, {"family": "Kiesler", "given": "Kevin", "initials": "K"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Azonbakin", "given": "Simon", "initials": "S"}, {"family": "B\u00f4\u017eikov\u00e1", "given": "Alexandra", "initials": "A"}, {"family": "Choma", "given": "Andrej", "initials": "A"}, {"family": "De Ungria", "given": "Maria Corazon", "initials": "MC"}, {"family": "Corradini", "given": "Beatrice", "initials": "B"}, {"family": "Cruz", "given": "Catarina", "initials": "C"}, {"family": "Dunkelmann", "given": "Bettina", "initials": "B"}, {"family": "Ferri", "given": "Gianmarco", "initials": "G"}, {"family": "Fleckhaus", "given": "Jan", "initials": "J"}, {"family": "Fragou", "given": "Domniki", "initials": "D"}, {"family": "Gaens", "given": "Noah", "initials": "N", "orcid": "0009-0006-4871-2287", "researcher": {"href": "https://publications.scilifelab.se/researcher/d2d331932b3b475bb6cce4b090a6fc4b.json"}}, {"family": "Gon\u00e7alves", "given": "Rita", "initials": "R"}, {"family": "Hava\u0161 Augu\u0161tin", "given": "Dubravka", "initials": "D"}, {"family": "Helm", "given": "Katharina", "initials": "K"}, {"family": "H\u00f6lzl-M\u00fcller", "given": "Petra", "initials": "P"}, {"family": "Kaliszan", "given": "Micha\u0142", "initials": "M"}, {"family": "Kasu", "given": "Mohaimin", "initials": "M"}, {"family": "Kovatsi", "given": "Leda", "initials": "L"}, {"family": "Lesaoana", "given": "Mpasi", "initials": "M"}, {"family": "Mizuno", "given": "Natsuko", "initials": "N"}, {"family": "Neuhuber", "given": "Franz", "initials": "F"}, {"family": "Nov\u00e1\u010dkov\u00e1", "given": "Jana", "initials": "J"}, {"family": "\u0147u\u0148ukov\u00e1", "given": "Alena", "initials": "A"}, {"family": "Pamjav", "given": "Horolma", "initials": "H"}, {"family": "Parson", "given": "Walther", "initials": "W", "orcid": "0000-0002-5692-2392", "researcher": {"href": "https://publications.scilifelab.se/researcher/84574a9a6f03419ea3a37a6dd0470082.json"}}, {"family": "Ramankulov", "given": "Yerlan", "initials": "Y"}, {"family": "Rangel Villalobos", "given": "H\u00e9ctor", "initials": "H"}, {"family": "R\u0119ba\u0142a", "given": "Krzysztof", "initials": "K"}, {"family": "Rootsi", "given": "Siiri", "initials": "S"}, {"family": "Salvador", "given": "Jazelyn", "initials": "J", "orcid": "0000-0003-0223-4532", "researcher": {"href": "https://publications.scilifelab.se/researcher/146e5af0a5f7419fab85f5a8cb41c40e.json"}}, {"family": "\u0160arac", "given": "Jelena", "initials": "J"}, {"family": "Steffen", "given": "Carolyn R", "initials": "CR"}, {"family": "Stenzl", "given": "Vlastimil", "initials": "V"}, {"family": "T\u00f6r\u00f6k", "given": "Tibor", "initials": "T"}, {"family": "Villems", "given": "Richard", "initials": "R"}, {"family": "Watahiki", "given": "Haruhiko", "initials": "H"}, {"family": "Zhabagin", "given": "Maxat", "initials": "M", "orcid": "0000-0003-3414-0610", "researcher": {"href": "https://publications.scilifelab.se/researcher/62105b830a024d5487243c2de9221778.json"}}, {"family": "Schneider", "given": "Peter M", "initials": "PM"}, {"family": "Kayser", "given": "Manfred", "initials": "M", "orcid": "0000-0002-4958-847X", "researcher": {"href": "https://publications.scilifelab.se/researcher/17043e6d1c884aaab77836046954459d.json"}}], "type": "journal article", "published": "2025-07-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "33", "issue": "7", "pages": "904-912", "issn-l": "1018-4813"}, "abstract": "For decades, there has been scientific interest in the variation and geographic distribution of paternal lineages associated with the human Y chromosome. However, the relevant data have been dispersed across numerous publications, making it difficult to consolidate. Additionally, understanding the relationships between different variants, and the tools used to analyze them, have evolved over time, further complicating efforts to harmonize this information. The Universal Y-SNP Database (UYSD) marks a substantial advancement by providing a comprehensive and accessible platform for Y-SNP and haplogroup data from populations around the world. UYSD harmonizes diverse datasets into a unified repository, facilitating the exploration of global Y-chromosomal variation. The platform handles data generated with both high- and low-throughput technology and is compatible with the automated analysis software tool, Yleaf v3. Key functionalities include the ability to: i) visualize haplogroup distributions on an interactive world map, ii) estimate haplogroup frequencies in geographic regions with sparse data through interpolation, and iii) display detailed phylogenetic trees of Y-chromosomal haplogroups. Currently, UYSD encompasses data from over 6,600 males across 27 populations. This dataset largely aligns with known global Y-haplogroup patterns, but also reveals unexplored finer-scale geographic variations. While the present dataset is largely European-centered, UYSD is designed for ongoing expansion by the scientific community, aiming to include more global data and higher-resolution population sequencing data. The platform thus offers valuable insights into human genetic diversity and migration patterns, serving several fields of research such as: human population genetics, genetic anthropology, ancient DNA analysis and forensic genetics.", "doi": "10.1038/s41431-025-01854-5", "pmid": "40341774", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12229683"}, {"db": "pii", "key": "10.1038/s41431-025-01854-5"}], "notes": [], "created": "2025-08-19T14:00:52.158Z", "modified": "2025-08-19T14:00:52.819Z"}, {"entity": "publication", "iuid": "721cdb8f88d04033a4d1712ca70be216", "links": {"self": {"href": "https://publications.scilifelab.se/publication/721cdb8f88d04033a4d1712ca70be216.json"}, "display": {"href": "https://publications.scilifelab.se/publication/721cdb8f88d04033a4d1712ca70be216"}}, "title": "EMD missense variant causes X-linked isolated dilated cardiomyopathy with myocardial emerin deficiency.", "authors": [{"family": "Bulmer", "given": "Linda", "initials": "L", "orcid": "0009-0001-5119-1156", "researcher": {"href": "https://publications.scilifelab.se/researcher/147a202ba3f14c4e9063c6a2feaddeb6.json"}}, {"family": "Ljungman", "given": "Charlotta", "initials": "C", "orcid": "0000-0002-2785-1919", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f1722548cf24b6fb76bbfd196c63408.json"}}, {"family": "Hallin", "given": "Johan", "initials": "J"}, {"family": "Dahlberg", "given": "Pia", "initials": "P"}, {"family": "Polte", "given": "Christian L", "initials": "CL", "orcid": "0000-0001-7125-9747", "researcher": {"href": "https://publications.scilifelab.se/researcher/20a7519ac50d4ac8bd4fc7c986eefcd0.json"}}, {"family": "Hedberg-Oldfors", "given": "Carola", "initials": "C", "orcid": "0000-0002-7141-4185", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc67028bf0c04f1b9a73bac5e72f9897.json"}}, {"family": "Oldfors", "given": "Anders", "initials": "A"}, {"family": "Gummesson", "given": "Anders", "initials": "A", "orcid": "0000-0003-0024-960X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb164de27f2846328bb675876922a5fe.json"}}], "type": "journal article", "published": "2025-06-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "33", "issue": "6", "pages": "775-783", "issn-l": "1018-4813"}, "abstract": "Pathogenic variants in the EMD gene cause X-linked Emery-Dreifuss muscular dystrophy type 1 (EDMD1), typically presenting with joint contractures and skeletal muscle atrophy, followed by atrial arrhythmias, cardiac conduction defects, and atrial dilatation. Although an association with isolated dilated cardiomyopathy (DCM) has been suggested, evidence is currently insufficient to verify the gene-disease association. We investigated the causality of a missense variant, c.23C>G, p.Ser8Trp, in EMD in a large family with a history of DCM and suspected sudden cardiac death (SCD) in males. DCM was diagnosed in six hemizygous males aged 36-50 and detailed phenotyping identified end-stage heart failure, cardiac conduction defects, and ventricular arrhythmias as prominent features. Cardiac magnetic resonance imaging showed late gadolinium enhancement with mixed ischemic and non-ischemic patterns. Muscular dystrophy was absent in all six males, of whom five underwent neuromuscular examination including serum-creatine kinase measurement. Immunohistochemical analysis showed greatly reduced levels of emerin in both cardiac and skeletal muscle samples. The EMD variant c.23C>G co-segregated with DCM, with an estimated LOD score of 3.9 and full-likelihood Bayes factor of >2500:1 in favor of causality. Among the 17 heterozygous females, ages 20-87, one developed DCM at age 72. We concluded that the EMD c.23C>G missense variant is associated with DCM in the absence of muscular dystrophy, thereby providing new evidence of isolated DCM as a distinct cardiac EMD-phenotype, separate from EDMD1. The phenotypic similarities with LMNA-DCM, with a high risk of cardiac conduction defects and ventricular arrhythmias, might warrant early interventions to prevent SCD.", "doi": "10.1038/s41431-025-01827-8", "pmid": "40065010", "labels": {"Clinical Genomics": "Service", "Clinical Genomics Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12185710"}, {"db": "pii", "key": "10.1038/s41431-025-01827-8"}], "notes": [], "created": "2025-07-08T13:52:10.967Z", "modified": "2025-11-04T11:32:46.724Z"}, {"entity": "publication", "iuid": "11bfd5f14ab244ff92ef3f20ae9e9e15", "links": {"self": {"href": "https://publications.scilifelab.se/publication/11bfd5f14ab244ff92ef3f20ae9e9e15.json"}, "display": {"href": "https://publications.scilifelab.se/publication/11bfd5f14ab244ff92ef3f20ae9e9e15"}}, "title": "Identification of biallelic POLA2 variants in two families with an autosomal recessive telomere biology disorder.", "authors": [{"family": "Kvarnung", "given": "Malin", "initials": "M"}, {"family": "Pettersson", "given": "Maria", "initials": "M"}, {"family": "Chun-On", "given": "Pattra", "initials": "P"}, {"family": "Rafati", "given": "Maryam", "initials": "M", "orcid": "0000-0001-7118-3412", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c0841d69cd04a5ea7292b73726b408a.json"}}, {"family": "McReynolds", "given": "Lisa J", "initials": "LJ", "orcid": "0000-0002-1018-1453", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf05c99cb8d34fa2ab0f09739da95295.json"}}, {"family": "Norberg", "given": "Anna", "initials": "A"}, {"family": "Moura", "given": "Pedro Luis", "initials": "PL", "orcid": "0000-0002-0493-5394", "researcher": {"href": "https://publications.scilifelab.se/researcher/12216bfd20fa4056b844842908efc829.json"}}, {"family": "Pesonen", "given": "Ida", "initials": "I"}, {"family": "Chaireti", "given": "Roza", "initials": "R"}, {"family": "Gr\u00f6nros S\u00f6derholm", "given": "Boa", "initials": "B"}, {"family": "Burlin", "given": "Julia", "initials": "J"}, {"family": "Ryd\u00e9n", "given": "Jenny", "initials": "J"}, {"family": "Lindberg", "given": "Eva Hellstr\u00f6m", "initials": "EH"}, {"family": "Giri", "given": "Neelam", "initials": "N"}, {"family": "Savage", "given": "Sharon A", "initials": "SA", "orcid": "0000-0001-6006-0740", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ebbcf2fee6945d2b1173ff0e4109674.json"}}, {"family": "Agarwal", "given": "Suneet", "initials": "S"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Tesi", "given": "Bianca", "initials": "B", "orcid": "0000-0002-8253-2507", "researcher": {"href": "https://publications.scilifelab.se/researcher/96a994cd257c4833a4efe79e26b900ff.json"}}], "type": "journal article", "published": "2025-05-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "33", "issue": "5", "pages": "580-587", "issn-l": "1018-4813"}, "abstract": "POLA2 encodes the accessory subunit of DNA polymerase \u03b1 (pol\u03b1)/primase, which is crucial for telomere C-strand fill-in. Incomplete fill-in of the C-rich telomeric strand after DNA replication has been proposed as a mechanism for Coats plus syndrome, a phenotype within the broader spectrum of telomere biology disorders (TBD). Coats plus syndrome has so far been associated with pathogenic variants in POT1, CTC1, and STN1. Here we report the findings of biallelic deleterious rare variants in POLA2 gene detected by whole genome sequencing and segregation analysis in five young adults from two unrelated families. All five individuals displayed abnormally short telomeres and a clinical phenotype suggesting a TBD disorder with Coats plus features including retinal and gastrointestinal telangiectasias. Our results suggest POLA2 as a novel autosomal recessive gene for a TBD with Coats plus features.", "doi": "10.1038/s41431-024-01722-8", "pmid": "39616267", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12048608"}, {"db": "pii", "key": "10.1038/s41431-024-01722-8"}], "notes": [], "created": "2025-11-18T20:43:12.167Z", "modified": "2025-11-18T20:44:44.102Z"}, {"entity": "publication", "iuid": "c301b4d4c3a547c0b128bb82f1379493", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c301b4d4c3a547c0b128bb82f1379493.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c301b4d4c3a547c0b128bb82f1379493"}}, "title": "Gustavson syndrome is caused by an in-frame deletion in RBMX associated with potentially disturbed SH3 domain interactions.", "authors": [{"family": "Johansson", "given": "Josefin", "initials": "J", "orcid": "0000-0002-5152-4096", "researcher": {"href": "https://publications.scilifelab.se/researcher/e568827124304b769a3f336d76b6954e.json"}}, {"family": "Lid\u00e9us", "given": "Sarah", "initials": "S"}, {"family": "Frykholm", "given": "Carina", "initials": "C"}, {"family": "Gunnarsson", "given": "Cecilia", "initials": "C", "orcid": "0000-0001-9474-6820", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed1a42fede5f4f6d87c20d6bb9f694de.json"}}, {"family": "Mihalic", "given": "Filip", "initials": "F", "orcid": "0000-0002-6840-2319", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f57a961e98e4e15b1b96ec8efc95d4f.json"}}, {"family": "Gudmundsson", "given": "Sanna", "initials": "S", "orcid": "0000-0002-2332-074X", "researcher": {"href": "https://publications.scilifelab.se/researcher/adb097c987504b2ca309e5f4e1cea5d2.json"}}, {"family": "Ekvall", "given": "Sara", "initials": "S"}, {"family": "Molin", "given": "Anna-Maja", "initials": "AM"}, {"family": "Pham", "given": "Mai", "initials": "M"}, {"family": "Vihinen", "given": "Mauno", "initials": "M", "orcid": "0000-0002-9614-7976", "researcher": {"href": "https://publications.scilifelab.se/researcher/250999f129ad4b4cb6e7e14c96988db9.json"}}, {"family": "Lagerstedt-Robinson", "given": "Kristina", "initials": "K"}, {"family": "Nordgren", "given": "Ann", "initials": "A"}, {"family": "Jemth", "given": "Per", "initials": "P"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Wilbe", "given": "Maria", "initials": "M"}, {"family": "Bondeson", "given": "Marie-Louise", "initials": "ML", "orcid": "0000-0002-3391-5341", "researcher": {"href": "https://publications.scilifelab.se/researcher/9bcb92e271664d9a83e618d5f3e43200.json"}}], "type": "journal article", "published": "2024-03-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "issn-l": "1018-4813", "volume": "32", "issue": "3", "pages": "333-341"}, "abstract": "RNA binding motif protein X-linked (RBMX) encodes the heterogeneous nuclear ribonucleoprotein G (hnRNP G) that regulates splicing, sister chromatid cohesion and genome stability. RBMX knock down experiments in various model organisms highlight the gene's importance for brain development. Deletion of the RGG/RG motif in hnRNP G has previously been associated with Shashi syndrome, however involvement of other hnRNP G domains in intellectual disability remain unknown. In the current study, we present the underlying genetic and molecular cause of Gustavson syndrome. Gustavson syndrome was first reported in 1993 in a large Swedish five-generation family presented with profound X-linked intellectual disability and an early death. Extensive genomic analyses of the family revealed hemizygosity for a novel in-frame deletion in RBMX in affected individuals (NM_002139.4; c.484_486del, p.(Pro162del)). Carrier females were asymptomatic and presented with skewed X-chromosome inactivation, indicating silencing of the pathogenic allele. Affected individuals presented minor phenotypic overlap with Shashi syndrome, indicating a different disease-causing mechanism. Investigation of the variant effect in a neuronal cell line (SH-SY5Y) revealed differentially expressed genes enriched for transcription factors involved in RNA polymerase II transcription. Prediction tools and a fluorescence polarization assay imply a novel SH3-binding motif of hnRNP G, and potentially a reduced affinity to SH3 domains caused by the deletion. In conclusion, we present a novel in-frame deletion in RBMX segregating with Gustavson syndrome, leading to disturbed RNA polymerase II transcription, and potentially reduced SH3 binding. The results indicate that disruption of different protein domains affects the severity of RBMX-associated intellectual disabilities.", "doi": "10.1038/s41431-023-01392-y", "pmid": "37277488", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Collaborative", "National Genomics Infrastructure": "Service", "Clinical Genomics Stockholm": "Service", "NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10923852"}, {"db": "pii", "key": "10.1038/s41431-023-01392-y"}], "notes": [], "created": "2023-08-15T07:12:40.774Z", "modified": "2024-11-25T10:15:29.202Z"}, {"entity": "publication", "iuid": "a74da9e4e62f4b18b4f94979e78bf749", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a74da9e4e62f4b18b4f94979e78bf749.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a74da9e4e62f4b18b4f94979e78bf749"}}, "title": "Ribonuclease inhibitor 1 (RNH1) deficiency cause congenital cataracts and global developmental delay with infection-induced psychomotor regression and anemia.", "authors": [{"family": "Hedberg-Oldfors", "given": "Carola", "initials": "C", "orcid": "0000-0002-7141-4185", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc67028bf0c04f1b9a73bac5e72f9897.json"}}, {"family": "Mitra", "given": "Sanhita", "initials": "S"}, {"family": "Molinaro", "given": "Angela", "initials": "A"}, {"family": "Visuttijai", "given": "Kittichate", "initials": "K", "orcid": "0000-0002-4800-8533", "researcher": {"href": "https://publications.scilifelab.se/researcher/f41f59ad2b0a4e1c95b0cc9cf109f6fa.json"}}, {"family": "Fogelstrand", "given": "Linda", "initials": "L", "orcid": "0000-0003-3698-8519", "researcher": {"href": "https://publications.scilifelab.se/researcher/f39ff709aa0646b8ad5e520780a0ad49.json"}}, {"family": "Oldfors", "given": "Anders", "initials": "A"}, {"family": "Sterky", "given": "Fredrik H", "initials": "FH"}, {"family": "Darin", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2023-08-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "31", "issue": "8", "pages": "887-894", "issn-l": "1018-4813"}, "abstract": "Ribonuclease inhibitor 1, also known as angiogenin inhibitor 1, encoded by RNH1, is a ubiquitously expressed leucine-rich repeat protein, which is highly conserved in mammalian species. Inactivation of rnh1 in mice causes an embryonically lethal anemia, but the exact biological function of RNH1 in humans remains unknown and no human genetic disease has so far been associated with RNH1. Here, we describe a family with two out of seven siblings affected by a disease characterized by congenital cataract, global developmental delay, myopathy and psychomotor deterioration, seizures and periodic anemia associated with upper respiratory tract infections. A homozygous splice-site variant (c.615-2A > C) in RNH1 segregated with the disease. Sequencing of RNA derived from patient fibroblasts and cDNA analysis of skeletal muscle mRNA showed aberrant splicing with skipping of exon 7. Western blot analysis revealed a total lack of the RNH1 protein. Functional analysis revealed that patient fibroblasts were more sensitive to RNase A exposure, and this phenotype was reversed by transduction with a lentivirus expressing RNH1 to complement patient cells. Our results demonstrate that loss-of-function of RNH1 in humans is associated with a multiorgan developmental disease with recessive inheritance. It may be speculated that the infection-induced deterioration resulted from an increased susceptibility toward extracellular RNases and/or other inflammatory responses normally kept in place by the RNase inhibitor RNH1.", "doi": "10.1038/s41431-023-01327-7", "pmid": "36935417", "labels": {"Clinical Genomics Gothenburg": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10400601"}, {"db": "pii", "key": "10.1038/s41431-023-01327-7"}], "notes": [], "created": "2023-11-30T22:32:46.635Z", "modified": "2023-11-30T22:32:46.676Z"}, {"entity": "publication", "iuid": "cb66d309355e422595b2415e469832ec", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cb66d309355e422595b2415e469832ec.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cb66d309355e422595b2415e469832ec"}}, "title": "Phylogenetic history of patrilineages rare in northern and eastern Europe from large-scale re-sequencing of human Y-chromosomes.", "authors": [{"family": "Ilum\u00e4e", "given": "Anne-Mai", "initials": "AM", "orcid": "0000-0001-6920-1335", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e813084669c4f039d3048a1092b23ea.json"}}, {"family": "Post", "given": "Helen", "initials": "H"}, {"family": "Flores", "given": "Rodrigo", "initials": "R", "orcid": "0000-0002-0965-5973", "researcher": {"href": "https://publications.scilifelab.se/researcher/724ea06ff41841fe8bc229de46e9676f.json"}}, {"family": "Karmin", "given": "Monika", "initials": "M", "orcid": "0000-0001-9827-5579", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ea80a37e01c41fda86a46e82ba1bb0e.json"}}, {"family": "Sahakyan", "given": "Hovhannes", "initials": "H", "orcid": "0000-0003-1596-2838", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e6743fb44d14252ac3b64ff10c022e2.json"}}, {"family": "Mondal", "given": "Mayukh", "initials": "M"}, {"family": "Montinaro", "given": "Francesco", "initials": "F"}, {"family": "Saag", "given": "Lauri", "initials": "L"}, {"family": "Bormans", "given": "Concetta", "initials": "C"}, {"family": "Sanchez", "given": "Luisa Fernanda", "initials": "LF"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Kals", "given": "Mart", "initials": "M"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R"}, {"family": "Pagani", "given": "Luca", "initials": "L", "orcid": "0000-0002-6639-524X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c102d2c5954a406699ec87c204c65440.json"}}, {"family": "Behar", "given": "Doron M", "initials": "DM"}, {"family": "Rootsi", "given": "Siiri", "initials": "S"}, {"family": "Villems", "given": "Richard", "initials": "R"}], "type": "journal article", "published": "2021-10-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "29", "issue": "10", "pages": "1510-1519", "issn-l": "1018-4813"}, "abstract": "The most frequent Y-chromosomal (chrY) haplogroups in northern and eastern Europe (NEE) are well-known and thoroughly characterised. Yet a considerable number of men in every population carry rare paternal lineages with estimated frequencies around 5%. So far, limited sample-sizes and insufficient resolution of genotyping have obstructed a truly comprehensive look into the variety of rare paternal lineages segregating within populations and potential signals of population history that such lineages might convey. Here we harness the power of massive re-sequencing of human Y chromosomes to identify previously unknown population-specific clusters among rare paternal lineages in NEE. We construct dated phylogenies for haplogroups E2-M215, J2-M172, G-M201 and Q-M242 on the basis of 421 (of them 282 novel) high-coverage chrY sequences collected from large-scale databases focusing on populations of NEE. Within these otherwise rare haplogroups we disclose lineages that began to radiate ~1-3 thousand years ago in Estonia and Sweden and reveal male phylogenetic patterns testifying of comparatively recent local demographic expansions. Conversely, haplogroup Q lineages bear evidence of ancient Siberian influence lingering in the modern paternal gene pool of northern Europe. We assess the possible direction of influx of ancestral carriers for some of these male lineages. In addition, we demonstrate the congruency of paternal haplogroup composition of our dataset with two independent population-based cohorts from Estonia and Sweden.", "doi": "10.1038/s41431-021-00897-8", "pmid": "33958743", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-021-00897-8"}, {"db": "pmc", "key": "PMC8484622"}], "notes": [], "created": "2021-06-18T06:29:57.845Z", "modified": "2021-11-10T12:25:00.508Z"}, {"entity": "publication", "iuid": "9c860be452904f5ea6c7c6b8ce7bdacc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9c860be452904f5ea6c7c6b8ce7bdacc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9c860be452904f5ea6c7c6b8ce7bdacc"}}, "title": "A MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis.", "authors": [{"family": "de Boer", "given": "Elke", "initials": "E"}, {"family": "Ockeloen", "given": "Charlotte W", "initials": "CW", "orcid": "0000-0003-0329-1520", "researcher": {"href": "https://publications.scilifelab.se/researcher/b88b912fef124652b0ad4d3df38c9f44.json"}}, {"family": "Matalonga", "given": "Leslie", "initials": "L"}, {"family": "Horvath", "given": "Rita", "initials": "R", "orcid": "0000-0002-9841-170X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1cd1176b50342f7a6c2f78a00c1080e.json"}}, {"family": "Solve-RD SNV-indel working group", "given": "", "initials": ""}, {"family": "Rodenburg", "given": "Richard J", "initials": "RJ", "orcid": "0000-0001-5227-3527", "researcher": {"href": "https://publications.scilifelab.se/researcher/493a079d6d0c4d2a9091fc38543b7d87.json"}}, {"family": "Coenen", "given": "Marieke J H", "initials": "MJH"}, {"family": "Janssen", "given": "Mirian", "initials": "M"}, {"family": "Henssen", "given": "Dylan", "initials": "D"}, {"family": "Gilissen", "given": "Christian", "initials": "C", "orcid": "0000-0003-1693-9699", "researcher": {"href": "https://publications.scilifelab.se/researcher/8facdfb49b114b7b9400dd8d1b93b298.json"}}, {"family": "Steyaert", "given": "Wouter", "initials": "W", "orcid": "0000-0001-8393-0788", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9106598269341509cc35585711351e3.json"}}, {"family": "Paramonov", "given": "Ida", "initials": "I"}, {"family": "Solve-RD-DITF-ITHACA", "given": "", "initials": ""}, {"family": "Trimouille", "given": "Aur\u00e9lien", "initials": "A", "orcid": "0000-0002-3457-5684", "researcher": {"href": "https://publications.scilifelab.se/researcher/11cd0853c4ad49678180c41b97a88850.json"}}, {"family": "Kleefstra", "given": "Tjitske", "initials": "T"}, {"family": "Verloes", "given": "Alain", "initials": "A", "orcid": "0000-0003-4819-0264", "researcher": {"href": "https://publications.scilifelab.se/researcher/1326e4bc6d764442b2fd851888c84f67.json"}}, {"family": "Vissers", "given": "Lisenka E L M", "initials": "LELM", "orcid": "0000-0001-6470-5497", "researcher": {"href": "https://publications.scilifelab.se/researcher/495b4d9a7db144a08ed311aced872c2a.json"}}], "type": "journal article", "published": "2021-09-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "29", "issue": "9", "pages": "1359-1368", "issn-l": "1018-4813"}, "abstract": "The genetic etiology of intellectual disability remains elusive in almost half of all affected individuals. Within the Solve-RD consortium, systematic re-analysis of whole exome sequencing (WES) data from unresolved cases with (syndromic) intellectual disability (n = 1,472 probands) was performed. This re-analysis included variant calling of mitochondrial DNA (mtDNA) variants, although mtDNA is not specifically targeted in WES. We identified a functionally relevant mtDNA variant in MT-TL1 (NC_012920.1:m.3291T > C; NC_012920.1:n.62T > C), at a heteroplasmy level of 22% in whole blood, in a 23-year-old male with severe intellectual disability, epilepsy, episodic headaches with emesis, spastic tetraparesis, brain abnormalities, and feeding difficulties. Targeted validation in blood and urine supported pathogenicity, with heteroplasmy levels of 23% and 58% in index, and 4% and 17% in mother, respectively. Interestingly, not all phenotypic features observed in the index have been previously linked to this MT-TL1 variant, suggesting either broadening of the m.3291T > C-associated phenotype, or presence of a co-occurring disorder. Hence, our case highlights the importance of underappreciated mtDNA variants identifiable from WES data, especially for cases with atypical mitochondrial phenotypes and their relatives in the maternal line.", "doi": "10.1038/s41431-021-00900-2", "pmid": "34075211", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-021-00900-2"}, {"db": "pmc", "key": "PMC8440635"}], "notes": [], "created": "2021-11-20T12:21:11.047Z", "modified": "2021-11-20T12:21:11.328Z"}, {"entity": "publication", "iuid": "b2d627809f54443d921bec29619bcc70", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b2d627809f54443d921bec29619bcc70.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b2d627809f54443d921bec29619bcc70"}}, "title": "Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.", "authors": [{"family": "Matalonga", "given": "Leslie", "initials": "L"}, {"family": "Hern\u00e1ndez-Ferrer", "given": "Carles", "initials": "C", "orcid": "0000-0002-8029-7160", "researcher": {"href": "https://publications.scilifelab.se/researcher/9716a4b2dec6496f93e5ea21b1fde8ed.json"}}, {"family": "Piscia", "given": "Davide", "initials": "D"}, {"family": "Solve-RD SNV-indel working group", "given": "", "initials": ""}, {"family": "Sch\u00fcle", "given": "Rebecca", "initials": "R"}, {"family": "Synofzik", "given": "Matthis", "initials": "M", "orcid": "0000-0002-2280-7273", "researcher": {"href": "https://publications.scilifelab.se/researcher/7005e3844fd34960a2045bb7febeec57.json"}}, {"family": "T\u00f6pf", "given": "Ana", "initials": "A"}, {"family": "Vissers", "given": "Lisenka E L M", "initials": "LELM", "orcid": "0000-0001-6470-5497", "researcher": {"href": "https://publications.scilifelab.se/researcher/495b4d9a7db144a08ed311aced872c2a.json"}}, {"family": "de Voer", "given": "Richarda", "initials": "R", "orcid": "0000-0002-8222-0343", "researcher": {"href": "https://publications.scilifelab.se/researcher/baef9b412cbf4b1783f6a1c64913fb30.json"}}, {"family": "Solve-RD DITF-GENTURIS", "given": "", "initials": ""}, {"family": "Solve-RD DITF-ITHACA", "given": "", "initials": ""}, {"family": "Solve-RD DITF-euroNMD", "given": "", "initials": ""}, {"family": "Solve-RD DITF-RND", "given": "", "initials": ""}, {"family": "Tonda", "given": "Raul", "initials": "R"}, {"family": "Laurie", "given": "Steven", "initials": "S"}, {"family": "Fernandez-Callejo", "given": "Marcos", "initials": "M"}, {"family": "Pic\u00f3", "given": "Daniel", "initials": "D"}, {"family": "Garcia-Linares", "given": "Carles", "initials": "C"}, {"family": "Papakonstantinou", "given": "Anastasios", "initials": "A"}, {"family": "Corv\u00f3", "given": "Alberto", "initials": "A"}, {"family": "Joshi", "given": "Ricky", "initials": "R", "orcid": "0000-0003-4463-0453", "researcher": {"href": "https://publications.scilifelab.se/researcher/00d346b9d3a04ddbaaccd612895f7136.json"}}, {"family": "Diez", "given": "Hector", "initials": "H"}, {"family": "Gut", "given": "Ivo", "initials": "I", "orcid": "0000-0001-7219-632X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c14600c4e0d54a7aae393c728d9af088.json"}}, {"family": "Hoischen", "given": "Alexander", "initials": "A"}, {"family": "Graessner", "given": "Holm", "initials": "H", "orcid": "0000-0001-9803-7183", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb6f274e7f494b8f879a92f2ebc0bf30.json"}}, {"family": "Beltran", "given": "Sergi", "initials": "S", "orcid": "0000-0002-2810-3445", "researcher": {"href": "https://publications.scilifelab.se/researcher/86f06a2de0b14260b5bc42c382a83c88.json"}}, {"family": "Solve-RD Consortia", "given": "", "initials": ""}], "type": "journal article", "published": "2021-09-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "29", "issue": "9", "pages": "1337-1347", "issn-l": "1018-4813"}, "abstract": "Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics.", "doi": "10.1038/s41431-021-00852-7", "pmid": "34075210", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-021-00852-7"}, {"db": "pmc", "key": "PMC8440686"}], "notes": [], "created": "2021-11-20T12:21:00.311Z", "modified": "2021-11-20T12:21:00.575Z"}, {"entity": "publication", "iuid": "627122d3b7f5410f829395df31d053e9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/627122d3b7f5410f829395df31d053e9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/627122d3b7f5410f829395df31d053e9"}}, "title": "Taste perception and lifestyle: insights from phenotype and genome data among Africans and Asians.", "authors": [{"family": "Sj\u00f6strand", "given": "Agn\u00e8s E", "initials": "AE"}, {"family": "Sj\u00f6din", "given": "Per", "initials": "P"}, {"family": "Hegay", "given": "Tatyana", "initials": "T"}, {"family": "Nikolaeva", "given": "Anna", "initials": "A"}, {"family": "Shayimkulov", "given": "Farhad", "initials": "F"}, {"family": "Blum", "given": "Michael G B", "initials": "MGB"}, {"family": "Heyer", "given": "Evelyne", "initials": "E", "orcid": "0000-0002-0266-3196", "researcher": {"href": "https://publications.scilifelab.se/researcher/aaa9ddd4afef4d28aa96f53bad9fc938.json"}}, {"family": "Jakobsson", "given": "Mattias", "initials": "M", "orcid": "0000-0001-7840-7853", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a4abe0fcb20492d9ec849c9fbf58a71.json"}}], "type": "journal article", "published": "2021-02-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "29", "issue": "2", "pages": "325-337", "issn-l": "1018-4813"}, "abstract": "Taste is essential for the interaction of animals with their food and has co-evolved with diet. Humans have peopled a large range of environments and present a wide range of diets, but little is known about the diversity and evolution of human taste perception. We measured taste recognition thresholds across populations differing in lifestyles (hunter gatherers and farmers from Central Africa, nomad herders, and farmers from Central Asia). We also generated genome-wide genotype data and performed association studies and selection scans in order to link the phenotypic variation in taste sensitivity with genetic variation. We found that hunter gatherers have lower overall sensitivity as well as lower sensitivity to quinine and fructose than their farming neighbors. In parallel, there is strong population divergence in genes associated with tongue morphogenesis and genes involved in the transduction pathway of taste signals in the African populations. We find signals of recent selection in bitter taste-receptor genes for all four populations. Enrichment analysis on association scans for the various tastes confirmed already documented associations and revealed novel GO terms that are good candidates for being involved in taste perception. Our framework permitted us to gain insight into the genetic basis of taste sensitivity variation across populations and lifestyles.", "doi": "10.1038/s41431-020-00736-2", "pmid": "33005019", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-020-00736-2"}, {"db": "pmc", "key": "PMC7868368"}], "notes": [], "created": "2020-10-20T06:59:23.977Z", "modified": "2024-01-16T13:48:40.806Z"}, {"entity": "publication", "iuid": "5ea3fa61d27c411cb95d6ae10c2cd99d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5ea3fa61d27c411cb95d6ae10c2cd99d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5ea3fa61d27c411cb95d6ae10c2cd99d"}}, "title": "SweHLA: the high confidence HLA typing bio-resource drawn from 1000 Swedish genomes.", "authors": [{"family": "Nordin", "given": "Jessika", "initials": "J", "orcid": "0000-0002-8414-2190", "researcher": {"href": "https://publications.scilifelab.se/researcher/2603df7f3ff84e6980605b9e8eef4c2f.json"}}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Meadows", "given": "Jennifer R S", "initials": "JRS"}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "issn-l": "1018-4813", "volume": "28", "issue": "5", "pages": "627-635"}, "abstract": "There is a need to accurately call human leukocyte antigen (HLA) genes from existing short-read sequencing data, however there is no single solution that matches the gold standard of Sanger sequenced lab typing. Here we aimed to combine results from available software programs, minimizing the biases of applied algorithm and HLA reference. The result is a robust HLA population resource for the published 1000 Swedish genomes, and a framework for future HLA interrogation. HLA 2nd-field alleles were called using four imputation and inference methods for the classical eight genes (class I: HLA-A, HLA-B, HLA-C; class II: HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1). A high confidence population set (SweHLA) was determined using an n-1 concordance rule for class I (four software) and class II (three software) alleles. Results were compared across populations and individual programs benchmarked to SweHLA. Per gene, 875 to 988 of the 1000 samples were genotyped in SweHLA; 920 samples had at least seven loci called. While a small fraction of reference alleles were common to all software (class I = 1.9% and class II = 4.1%), this did not affect the overall call rate. Gene-level concordance was high compared to European populations (>0.83%), with COX and PGF the dominant SweHLA haplotypes. We noted that 15/18 discordant alleles (delta allele frequency >2) were previously reported as disease-associated. These differences could in part explain across-study genetic replication failures, reinforcing the need to use multiple software solutions. SweHLA demonstrates a way to use existing NGS data to generate a population resource agnostic to individual HLA software biases.", "doi": "10.1038/s41431-019-0559-2", "pmid": "31844174", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-019-0559-2"}, {"db": "pmc", "key": "PMC7170882"}], "notes": [], "created": "2020-02-11T10:04:25.991Z", "modified": "2021-11-10T12:51:33.748Z"}, {"entity": "publication", "iuid": "b5443abd00b749b6ae6e72151a971b87", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5443abd00b749b6ae6e72151a971b87.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5443abd00b749b6ae6e72151a971b87"}}, "title": "Longitudinal changes in the frequency of mosaic chromosome Y loss in peripheral blood cells of aging men varies profoundly between individuals.", "authors": [{"family": "Danielsson", "given": "Marcus", "initials": "M", "orcid": "0000-0003-4418-0165", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6b237ce613e4ef8a6d7ab2654c2c41e.json"}}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Davies", "given": "Hanna", "initials": "H"}, {"family": "Torabi Moghadam", "given": "Behrooz", "initials": "B"}, {"family": "Mattisson", "given": "Jonas", "initials": "J", "orcid": "0000-0002-4456-9667", "researcher": {"href": "https://publications.scilifelab.se/researcher/2672b9fa599b44a395d1a2f8f59a5949.json"}}, {"family": "Rychlicka-Buniowska", "given": "Edyta", "initials": "E"}, {"family": "Jaszczy\u0144ski", "given": "Janusz", "initials": "J"}, {"family": "Heintz", "given": "Julia", "initials": "J"}, {"family": "Lannfelt", "given": "Lars", "initials": "L"}, {"family": "Giedraitis", "given": "Vilmantas", "initials": "V"}, {"family": "Ingelsson", "given": "Martin", "initials": "M"}, {"family": "Dumanski", "given": "Jan P", "initials": "JP"}, {"family": "Forsberg", "given": "Lars A", "initials": "LA", "orcid": "0000-0002-1701-755X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ac2d8e983764a82982118b6db84029e.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "issn-l": "1018-4813", "volume": "28", "issue": "3", "pages": "349-357"}, "abstract": "Mosaic loss of chromosome Y (LOY) is the most common somatic genetic aberration and is associated with increased risk for all-cause mortality, various forms of cancer and Alzheimer's disease, as well as other common human diseases. By tracking LOY frequencies in subjects from which blood samples have been serially collected up to five times during up to 22 years, we observed a pronounced intra-individual variation of changes in the frequency of LOY within individual men over time. We observed that in some individuals the frequency of LOY in blood clearly progressed over time and that in other men, the frequency was constant or showed other types of longitudinal development. The predominant method used for estimating LOY is calculation of the median Log R Ratio of probes located in the male specific part of chromosome Y (mLRRY) from intensity data generated by SNP-arrays, which is difficult to interpret due to its logarithmic and inversed scale. We present here a formula to transform mLRRY-values to percentage of LOY that is a more comprehensible unit. The formula was derived using measurements of LOY from matched samples analysed using SNP-array, whole genome sequencing and a new AMELX/AMELY-based assay for droplet digital PCR. The methods described could be applied for analyses of the vast amount of SNP-array data already generated in the scientific community, allowing further discoveries of LOY associated diseases and outcomes.", "doi": "10.1038/s41431-019-0533-z", "pmid": "31654039", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-019-0533-z"}, {"db": "pmc", "key": "PMC7028735"}], "notes": [], "created": "2019-10-30T13:13:11.626Z", "modified": "2024-01-16T13:48:42.853Z"}, {"entity": "publication", "iuid": "f0b61c7f79764e5b80784ea748d8ef40", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0b61c7f79764e5b80784ea748d8ef40.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0b61c7f79764e5b80784ea748d8ef40"}}, "title": "Linkage analysis revealed risk loci on 6p21 and 18p11.2-q11.2 in familial colon and rectal cancer, respectively.", "authors": [{"family": "von Holst", "given": "Susanna", "initials": "S"}, {"family": "Jiao", "given": "Xiang", "initials": "X"}, {"family": "Liu", "given": "Wen", "initials": "W"}, {"family": "Kontham", "given": "Vinaykumar", "initials": "V"}, {"family": "Thutkawkorapin", "given": "Jessada", "initials": "J"}, {"family": "Ringdahl", "given": "Jenny", "initials": "J"}, {"family": "Bryant", "given": "Patrick", "initials": "P"}, {"family": "Lindblom", "given": "Annika", "initials": "A"}], "type": "journal article", "published": "2019-08-00", "journal": {"volume": "27", "issn": "1476-5438", "issue": "8", "pages": "1286-1295", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Colorectal cancer (CRC) is one of the major cancer types in the western world including Sweden. However, known genetic risk factors could only explain a limited part of heritability of the disease. Moreover, colon and rectal cancers are habitually discussed as one entity, colorectal cancer, although different carcinogenesis has been recognized. A genome-wide linkage scan in 32 colon- and 56 rectal cancer families from Sweden was performed based on 475 non-FAP/HNPCC patients genotyped using SNP arrays. A maximum HLOD of 2.50 at locus 6p21.1-p12.1 and a HLOD of 2.56 at 18p11.2 was obtained for colon and rectal cancer families, respectively. Exome sequencing over the regions of interest in 12 patients from six families identified 22 and 25 candidate risk variants for colon and rectal cancer, respectively. Haplotype association analysis in the two regions was carried out between additional 477 familial CRC cases and 4780 controls and suggested candidate haplotypes possibly associated with CRC risk. This study suggested two new linkage regions for colon cancer and rectal cancer with candidate predisposing variants. Further studies are required to elucidate the pathogenic mechanism of these regions and to pinpoint the causative genes.", "doi": "10.1038/s41431-019-0388-3", "pmid": "30952955", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-019-0388-3"}], "notes": [], "created": "2019-08-13T12:15:30.342Z", "modified": "2024-01-16T13:48:44.038Z"}, {"entity": "publication", "iuid": "231ea4382fec40589e362e641083fa78", "links": {"self": {"href": "https://publications.scilifelab.se/publication/231ea4382fec40589e362e641083fa78.json"}, "display": {"href": "https://publications.scilifelab.se/publication/231ea4382fec40589e362e641083fa78"}}, "title": "A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts.", "authors": [{"family": "Farias", "given": "Fabiana H G", "initials": "FHG"}, {"family": "Dahlqvist", "given": "Johanna", "initials": "J"}, {"family": "Kozyrev", "given": "Sergey V", "initials": "SV"}, {"family": "Leonard", "given": "Dag", "initials": "D"}, {"family": "Wilbe", "given": "Maria", "initials": "M"}, {"family": "Abramov", "given": "Sergei N", "initials": "SN"}, {"family": "Alexsson", "given": "Andrei", "initials": "A"}, {"family": "Pielberg", "given": "Gerli R", "initials": "GR"}, {"family": "Hansson-Hamlin", "given": "Helene", "initials": "H"}, {"family": "Andersson", "given": "G\u00f6ran", "initials": "G"}, {"family": "Tandre", "given": "Karolina", "initials": "K"}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4dd47b8ca1436e8a26fdea33f5e7f6.json"}}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E"}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK"}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}], "type": "journal article", "published": "2019-03-00", "journal": {"volume": "27", "issn": "1476-5438", "issue": "3", "pages": "432-441", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical presentation and complex etiology involving the interplay between genetic, epigenetic, environmental and hormonal factors. Many common SNPs identified by genome wide-association studies (GWAS) explain only a small part of the disease heritability suggesting the contribution from rare genetic variants, undetectable in GWAS, and complex epistatic interactions. Using targeted re-sequencing of coding and conserved regulatory regions within and around 215 candidate genes selected on the basis of their known role in autoimmunity and genes associated with canine immune-mediated diseases, we identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1-10). Fisher's exact test revealed an association between the genetic variant and a triad of disease manifestations including Raynaud, anti-U1-ribonucleoprotein (anti-RNP), and anti-Smith (anti-Sm) antibodies (p = 0.00037) among the patients. The DNA-binding activity of the allele was further studied by EMSA, reporter assays, and minigenes. The region has properties of an active cell-specific enhancer, differentially affected by the alleles of rs200395694:G > T. In addition, the risk allele exerts an inhibitory effect on the splicing of the alternative tissue-specific isoform, and thus may modify the target gene set regulated by this isoform. These findings emphasize the potential of dissecting traits of complex diseases and correlating them with rare risk alleles with strong biological effects.", "doi": "10.1038/s41431-018-0297-x", "pmid": "30459414", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-018-0297-x"}, {"db": "pmc", "key": "PMC6460566"}], "notes": [], "created": "2018-11-28T07:46:41.045Z", "modified": "2024-01-16T13:48:44.647Z"}, {"entity": "publication", "iuid": "7891dd32a0fe42cda198089b6b8552e4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7891dd32a0fe42cda198089b6b8552e4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7891dd32a0fe42cda198089b6b8552e4"}}, "title": "Exploring rare and low-frequency variants in the Saguenay-Lac-Saint-Jean population identified genes associated with asthma and allergy traits.", "authors": [{"family": "Morin", "given": "Andr\u00e9anne", "initials": "A"}, {"family": "Madore", "given": "Anne-Marie", "initials": "AM"}, {"family": "Kwan", "given": "Tony", "initials": "T"}, {"family": "Ban", "given": "Maria", "initials": "M"}, {"family": "Partanen", "given": "Jukka", "initials": "J"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Sawcer", "given": "Stephen", "initials": "S"}, {"family": "Stunnenberg", "given": "Hendrik", "initials": "H"}, {"family": "Lathrop", "given": "Mark", "initials": "M"}, {"family": "Pastinen", "given": "Tomi", "initials": "T"}, {"family": "Laprise", "given": "Catherine", "initials": "C"}], "type": "journal article", "published": "2019-01-00", "journal": {"volume": "27", "issn": "1476-5438", "issue": "1", "pages": "90-101", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "The Saguenay-Lac-Saint-Jean (SLSJ) region is located in northeastern Quebec and is known for its unique demographic history and founder effect. As founder populations are enriched with population-specific variants, we characterized the variants distribution in SLSJ and compared it with four European populations (Finnish, Sweden, United Kingdom and France), of which the Finnish population is another founder population. Targeted sequencing of the coding and non-coding immune regulatory regions of the SLSJ asthma familial cohort and the four European populations were performed. Rare and low-frequency coding and non-coding regulatory variants identified in the SLSJ population were then investigated for variant- and gene-level associations with asthma and allergy-related traits (eosinophil percentage, immunoglobulin (Ig) E levels and lung function). Our data showed that (1) rare or deleterious variants were not enriched in the two founder populations as compared with the three non-founder European populations; (2) a larger proportion of founder population-specific variants occurred with higher frequencies; and (3) low-frequency variants appeared to be more deleterious. Furthermore, a rare variant, rs1386931, located in the 3'-UTR of CXCR6 and intron of FYCO1 was found to be associated with eosinophil percentage. Gene-based analyses identified NRP2, MRPL44 and SERPINE2 to be associated with various asthma and allergy-related traits. Our study demonstrated the usefulness of using a founder population to identify new genes associated with asthma and allergy-related traits; thus better understand the genes and pathways implicated in pathophysiology.", "doi": "10.1038/s41431-018-0266-4", "pmid": "30206357", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-018-0266-4"}, {"db": "pmc", "key": "PMC6303288"}], "notes": [], "created": "2019-04-23T09:51:30.738Z", "modified": "2021-07-07T14:57:19.973Z"}, {"entity": "publication", "iuid": "63a924bcbe104548a3e5ceccc51815f5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/63a924bcbe104548a3e5ceccc51815f5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/63a924bcbe104548a3e5ceccc51815f5"}}, "title": "Stereocilin gene variants associated with episodic vertigo: expansion of the DFNB16 phenotype.", "authors": [{"family": "Frykholm", "given": "Carina", "initials": "C"}, {"family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "researcher": {"href": "https://publications.scilifelab.se/researcher/3310cb2ab70f43d78cc7cd7e36ac8f83.json"}}, {"family": "Tomanovic", "given": "Tatjana", "initials": "T"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "case reports", "published": "2018-12-00", "journal": {"volume": "26", "issn": "1476-5438", "issue": "12", "title": "Eur. J. Hum. Genet.", "pages": "1871-1874", "issn-l": "1018-4813"}, "abstract": "Vestibular disorders comprise a heterogeneous group of diseases with transient or permanent loss of vestibular function. Vestibulopathy is in most cases associated with migraine, M\u00e9ni\u00e8re disease, hereditary ataxias, or sensorineural hearing loss. We identified two brothers and their first cousin affected by hearing loss and episodic vertigo. The brothers were homozygous STRC nonsense variant [c.4027 C > T, p.(Q1343*)], whereas their first cousin was compound heterozygous for the STRC nonsense variant and a 97 kb deletion spanning the entire STRC gene. Clinical investigations confirmed pathological vestibular responses in addition to a characteristic DFNB16 hearing loss. The STRC gene encodes Stereocilin in the cochlea and in the vestibular organ where it ensheathes the kinocilium of the otolithic membranes. Stereocilin is associated with the gel overlaying the vestibular kinocilia, suggesting a role for the protein in sensing balance and spatial orientation. Our findings support such a function for Stereocilin in the vestibular organ and expand the phenotype associated with DFNB16.", "doi": "10.1038/s41431-018-0256-6", "pmid": "30250054", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-018-0256-6"}, {"db": "pmc", "key": "PMC6244415"}], "notes": [], "created": "2018-11-08T13:16:49.023Z", "modified": "2024-01-16T13:48:44.990Z"}, {"entity": "publication", "iuid": "f6f95459ef4840abb63e336cfd3f033d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f6f95459ef4840abb63e336cfd3f033d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f6f95459ef4840abb63e336cfd3f033d"}}, "title": "\u03b3-glutamyl transpeptidase deficiency caused by a large homozygous intragenic deletion in GGT1.", "authors": [{"family": "Darin", "given": "Niklas", "initials": "N"}, {"family": "Leckstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Sikora", "given": "Per", "initials": "P", "orcid": "0000-0002-0049-1562", "researcher": {"href": "https://publications.scilifelab.se/researcher/beeaccd4a7ab4105be077ee778cf0507.json"}}, {"family": "Lindgren", "given": "Julia", "initials": "J"}, {"family": "Alm\u00e9n", "given": "Gabriella", "initials": "G"}, {"family": "Asin-Cayuela", "given": "Jorge", "initials": "J"}], "type": "journal article", "published": "2018-06-00", "journal": {"volume": "26", "issn": "1476-5438", "issue": "6", "pages": "808-817", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "\u03b3-Glutamyl transpeptidase deficiency (glutathionuria, OMIM 231950) is a rare disease, with only six patients reported in the literature, although this condition has probably been underdiagnosed due the difficulty to routinely analyze glutathione in clinical samples and to the fact that no genetic defect has been coupled to the disease so far. We report two siblings with mild psychomotor developmental delay and mild neurological symptoms, who presented a markedly increased excretion of glutathione in urine and a very low \u03b3-glutamyl transpeptidase activity in serum. Whole-genome sequencing revealed the presence of a 16.9 kb homozygous deletion in GGT1, one of the genes encoding enzymes with \u03b3-glutamyl transpeptidase activity in the human genome. Close analysis revealed the presence of a 13 bp insertion at the deletion junction. This is the first report of a genetic variant as the cause of glutathionuria. In addition, genetic characterization of the patients' parents and a healthy sibling has provided direct genetic evidence regarding the autosomal recessive nature of this disease.", "doi": "10.1038/s41431-018-0122-6", "pmid": "29483667", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-018-0122-6"}, {"db": "pmc", "key": "PMC5974402"}], "notes": [], "created": "2018-10-29T09:07:43.842Z", "modified": "2021-07-06T14:53:44.822Z"}, {"entity": "publication", "iuid": "f892ff63669141bc8f46e7fd8d8fde48", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f892ff63669141bc8f46e7fd8d8fde48.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f892ff63669141bc8f46e7fd8d8fde48"}}, "title": "SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population.", "authors": [{"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Dahlberg", "given": "Johan", "initials": "J"}, {"family": "Olason", "given": "Pall", "initials": "P"}, {"family": "Vezzi", "given": "Francesco", "initials": "F"}, {"family": "Karlsson", "given": "Robert", "initials": "R", "orcid": "0000-0002-8949-2587", "researcher": {"href": "https://publications.scilifelab.se/researcher/9df14bf33f3342408d624caa70d45b7c.json"}}, {"family": "Martin", "given": "Marcel", "initials": "M"}, {"family": "Viklund", "given": "Johan", "initials": "J"}, {"family": "K\u00e4h\u00e4ri", "given": "Andreas Kusalananda", "initials": "AK"}, {"family": "Lundin", "given": "P\u00e4r", "initials": "P"}, {"family": "Che", "given": "Huiwen", "initials": "H"}, {"family": "Thutkawkorapin", "given": "Jessada", "initials": "J"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Lampa", "given": "Samuel", "initials": "S"}, {"family": "Dahlberg", "given": "Mats", "initials": "M"}, {"family": "Hagberg", "given": "Jonas", "initials": "J", "orcid": "0000-0003-2370-6025", "researcher": {"href": "https://publications.scilifelab.se/researcher/181649773b3e451981f5ffb2da4c60b9.json"}}, {"family": "Jareborg", "given": "Niclas", "initials": "N", "orcid": "0000-0002-4520-044X", "researcher": {"href": "https://publications.scilifelab.se/researcher/09533c4bd4174ecab9ba866d22a1e585.json"}}, {"family": "Liljedahl", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-1250-392X", "researcher": {"href": "https://publications.scilifelab.se/researcher/241618974ae142b38e5fe84236819f2b.json"}}, {"family": "Jonasson", "given": "Inger", "initials": "I"}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Lundin", "given": "Sverker", "initials": "S"}, {"family": "Nilsson", "given": "Daniel", "initials": "D"}, {"family": "Nystedt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-7809-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0af5a168baa4b00a6fab8d3447ebfb4.json"}}, {"family": "Magnusson", "given": "Patrik Ke", "initials": "PK"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2017-11-00", "journal": {"volume": "25", "issn": "1476-5438", "issue": "11", "pages": "1253-1260", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.", "doi": "10.1038/ejhg.2017.130", "pmid": "28832569", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ejhg2017130"}, {"db": "pmc", "key": "PMC5765326"}], "notes": [], "created": "2017-08-24T14:18:14.989Z", "modified": "2024-01-16T13:48:47.338Z"}, {"entity": "publication", "iuid": "262ac673637b4c72b5b92692a8969ec7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/262ac673637b4c72b5b92692a8969ec7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/262ac673637b4c72b5b92692a8969ec7"}}, "title": "A novel splicing mutation in the IQSEC2 gene that modulates the phenotype severity in a family with intellectual disability.", "authors": [{"family": "Madrigal", "given": "Irene", "initials": "I"}, {"family": "Alvarez-Mora", "given": "Maria Isabel", "initials": "MI"}, {"family": "Rosell", "given": "Jordi", "initials": "J"}, {"family": "Rodr\u00edguez-Revenga", "given": "Laia", "initials": "L"}, {"family": "Karlberg", "given": "Olof", "initials": "O"}, {"family": "Sauer", "given": "Sascha", "initials": "S"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Mila", "given": "Montserrat", "initials": "M"}], "type": "journal article", "published": "2016-08-00", "journal": {"volume": "24", "issn": "1476-5438", "issue": "8", "pages": "1117-1123", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "The IQSEC2 gene is located on chromosome Xp11.22 and encodes a guanine nucleotide exchange factor for the ADP-ribosylation factor family of small GTPases. This gene is known to have a significant role in cytoskeletal organization, dendritic spine morphology and synaptic organization. Variants in IQSEC2 cause moderate to severe intellectual disability in males and a variable phenotype in females because this gene escapes from X-chromosome inactivation. Here we report on the first splicing variant in IQSEC2 (g.88032_88033del; NG_021296.1) that co-segregates in a family diagnosed with an X-linked form of ID. In a percentage of the cells, the variant activates an intraexonic splice acceptor site that abolishes 26 amino acids from the highly conserved PH domain of IQSEC2 and creates a premature stop codon 36 amino acids later in exon 13. Interestingly, the percentage of aberrant splicing seems to correlate with the severity of the disease in each patient. The impact of this variant in the target tissue is unknown, but we can hypothesize that these differences may be related to the amount of abnormal IQSEC2 transcript. To our knowledge, we are reporting a novel mechanism of IQSEC2 involvement in ID. Variants that affect splicing are related to many genetic diseases and the understanding of their role in disease expands potential opportunities for gene therapy. Modulation of aberrant splicing transcripts can become a potent therapeutic approach for many of these diseases.", "doi": "10.1038/ejhg.2015.267", "pmid": "26733290", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ejhg2015267"}, {"db": "pmc", "key": "PMC4970682"}], "notes": [], "created": "2017-05-03T13:01:34.185Z", "modified": "2021-07-07T15:11:02.350Z"}, {"entity": "publication", "iuid": "89c1a3d0dc754a759b2f8370bc029bef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/89c1a3d0dc754a759b2f8370bc029bef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/89c1a3d0dc754a759b2f8370bc029bef"}}, "title": "Association analysis of copy numbers of FC-gamma receptor genes for rheumatoid arthritis and other immune-mediated phenotypes.", "authors": [{"family": "Franke", "given": "Lude", "initials": "L"}, {"family": "el Bannoudi", "given": "Hanane", "initials": "H"}, {"family": "Jansen", "given": "Diahann T S L", "initials": "DT"}, {"family": "Kok", "given": "Klaas", "initials": "K"}, {"family": "Trynka", "given": "Gosia", "initials": "G"}, {"family": "Diogo", "given": "Dorothee", "initials": "D"}, {"family": "Swertz", "given": "Morris", "initials": "M"}, {"family": "Fransen", "given": "Karin", "initials": "K"}, {"family": "Knevel", "given": "Rachel", "initials": "R"}, {"family": "Gutierrez-Achury", "given": "Javier", "initials": "J"}, {"family": "\u00c4rlestig", "given": "Lisbeth", "initials": "L"}, {"family": "Greenberg", "given": "Jeffrey D", "initials": "JD"}, {"family": "Kremer", "given": "Joel", "initials": "J"}, {"family": "Pappas", "given": "Dimitrios A", "initials": "DA"}, {"family": "Kanterakis", "given": "Alexandros", "initials": "A"}, {"family": "Weersma", "given": "Rinse K", "initials": "RK"}, {"family": "van der Helm-van Mil", "given": "Annette H M", "initials": "AH"}, {"family": "Guryev", "given": "Viktor", "initials": "V"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S"}, {"family": "Gregersen", "given": "Peter K", "initials": "PK"}, {"family": "Plenge", "given": "Robert M", "initials": "RM"}, {"family": "Wijmenga", "given": "Cisca", "initials": "C"}, {"family": "Huizinga", "given": "Tom W-J", "initials": "TW"}, {"family": "Ioan-Facsinay", "given": "Andreea", "initials": "A"}, {"family": "Toes", "given": "Rene E M", "initials": "RE"}, {"family": "Zhernakova", "given": "Alexandra", "initials": "A"}], "type": "journal article", "published": "2016-02-00", "journal": {"volume": "24", "issn": "1476-5438", "issue": "2", "pages": "263-270", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Segmental duplications (SDs) comprise about 5% of the human genome and are enriched for immune genes. SD loci often show copy numbers variations (CNV), which are difficult to tag with genotyping methods. CNV in the Fc\u03b3 receptor region (FCGR) has been suggested to be associated with rheumatic diseases. The objective of this study was to delineate association of FCGR-CNV with rheumatoid arthritis (RA), coeliac disease and Inflammatory bowel disease incidence. We developed a method to accurately quantify CNV in SD loci based on the intensity values from the Immunochip platform and applied it to the FCGR locus. We determined the method's validity using three independent assays: segregation analysis in families, arrayCGH, and whole genome sequencing. Our data showed the presence of two separate CNVs in the FCGR locus. The first region encodes FCGR2A, FCGR3A and part of FCGR2C gene, the second encodes another part of FCGR2C, FCGR3B and FCGR2B. Analysis of CNV status in 4578 individuals with RA and 5457 controls indicated association of duplications in the FCGR3B gene in antibody-negative RA (P=0.002, OR=1.43). Deletion in FCGR3B was associated with increased risk of antibody-positive RA, consistently with previous reports (P=0.023, OR=1.23). A clear genotype-phenotype relationship was observed: CNV polymorphisms of the FCGR3A gene correlated to CD16A expression (encoded by FCGR3A) on CD8 T-cells. In conclusion, our method allows determining the CNV status of the FCGR locus, we identified association of CNV in FCGR3B to RA and showed a functional relationship between CNV in the FCGR3A gene and CD16A expression.", "doi": "10.1038/ejhg.2015.95", "pmid": "25966632", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "ejhg201595"}, {"db": "pmc", "key": "PMC4717214"}], "notes": [], "created": "2017-05-02T12:57:01.425Z", "modified": "2020-01-21T13:56:03.502Z"}, {"entity": "publication", "iuid": "75eed86d1a72489e8579fbd105541c14", "links": {"self": {"href": "https://publications.scilifelab.se/publication/75eed86d1a72489e8579fbd105541c14.json"}, "display": {"href": "https://publications.scilifelab.se/publication/75eed86d1a72489e8579fbd105541c14"}}, "title": "Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution.", "authors": [{"family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "researcher": {"href": "https://publications.scilifelab.se/researcher/3310cb2ab70f43d78cc7cd7e36ac8f83.json"}}, {"family": "Raykova", "given": "Doroteya", "initials": "D", "orcid": "0000-0001-6452-2199", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a81c40491e349178167f148f2351875.json"}}, {"family": "Gustafson", "given": "Elisabet", "initials": "E"}, {"family": "T\u00f3thov\u00e1", "given": "Iveta", "initials": "I"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Wanders", "given": "Alkwin", "initials": "A"}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2015-12-00", "journal": {"volume": "23", "issn": "1476-5438", "issue": "12", "pages": "1679-1683", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Familial visceral myopathy (FVM) is a rare heritable and heterogeneous condition due to impaired smooth muscle function. We identified a family segregating 11 individuals with a spectrum of visceral symptoms involving the small intestine, colon, biliary tract, urinary tract and uterus. Whole-exome sequencing revealed a novel heterozygous tandem base substitution c.806_807delinsAA (p.(Gly269Glu)) in ACTG2, encoding smooth muscle actin \u03b3-2, in affected family members. Variants in ACTG2 were recently identified in FVM with intestinal pseudo-obstruction as well as with the congenital megacystics-microcolon-intestinal hypoperistalsis syndrome. In our family, eight affected members presented with severe complications from the biliary and/or the urinary tracts in addition to gastrointestinal pseudo-obstructions. Furthermore, all affected mothers had a history of assisted deliveries owing to poor progress during labor and weak uterine contractions. The variable involvement of multiple smooth muscle-dependent organs in our family, including the biliary tract and the uterus, add to the phenotypic spectrum associated with ACTG2 missense variants.", "doi": "10.1038/ejhg.2015.49", "pmid": "25782675", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg201549"}, {"db": "pmc", "key": "PMC4795199"}], "notes": [], "created": "2017-05-02T12:57:23.795Z", "modified": "2021-07-07T14:37:06.508Z"}, {"entity": "publication", "iuid": "6d59b408a4ad4a77b4fbc7526f93c65e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6d59b408a4ad4a77b4fbc7526f93c65e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6d59b408a4ad4a77b4fbc7526f93c65e"}}, "title": "Exome sequencing followed by genotyping suggests SYPL2 as a susceptibility gene for morbid obesity.", "authors": [{"family": "Jiao", "given": "Hong", "initials": "H"}, {"family": "Arner", "given": "Peter", "initials": "P"}, {"family": "Gerdhem", "given": "Paul", "initials": "P"}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ"}, {"family": "N\u00e4slund", "given": "Erik", "initials": "E"}, {"family": "Thorell", "given": "Anders", "initials": "A"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Kere", "given": "Juha", "initials": "J"}, {"family": "Dahlman", "given": "Ingrid", "initials": "I"}], "type": "journal article", "published": "2015-09-00", "journal": {"volume": "23", "issn": "1476-5438", "issue": "9", "pages": "1216-1222", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Recently developed high-throughput sequencing technology shows power to detect low-frequency disease-causing variants by deep sequencing of all known exons. We used exome sequencing to identify variants associated with morbid obesity. DNA from 100 morbidly obese adult subjects and 100 controls were pooled (n=10/pool), subjected to exome capture, and subsequent sequencing. At least 100 million sequencing reads were obtained from each pool. After several filtering steps and comparisons of observed frequencies of variants between obese and non-obese control pools, we systematically selected 144 obesity-enriched non-synonymous, splicing site or 5' upstream single-nucleotide variants for validation. We first genotyped 494 adult subjects with morbid obesity and 496 controls. Five obesity-associated variants (nominal P-value<0.05) were subsequently genotyped in 1425 morbidly obese and 782 controls. Out of the five variants, only rs62623713:A>G (NM_001040709:c.A296G:p.E99G) was confirmed. rs62623713 showed strong association with body mass index (beta=2.13 (1.09, 3.18), P=6.28 \u00d7 10(-5)) in a joint analysis of all 3197 genotyped subjects and had an odds ratio of 1.32 for obesity association. rs62623713 is a low-frequency (2.9% minor allele frequency) non-synonymous variant (E99G) in exon 4 of the synaptophysin-like 2 (SYPL2) gene. rs62623713 was not covered by Illumina or Affymetrix genotyping arrays used in previous genome-wide association studies. Mice lacking Sypl2 has been reported to display reduced body weight. In conclusion, using exome sequencing we identified a low-frequency coding variant in the SYPL2 gene that was associated with morbid obesity. This gene may be involved in the development of excess body fat.", "doi": "10.1038/ejhg.2014.255", "pmid": "25406998", "labels": {"National Genomics Infrastructure": null, "Mutation Analysis Facility (MAF)": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "ejhg2014255"}, {"db": "pmc", "key": "PMC4538196"}], "notes": [], "created": "2017-05-02T12:57:26.447Z", "modified": "2020-01-21T13:56:02.860Z"}, {"entity": "publication", "iuid": "b459a8665151428aab83bdd1850ff53b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b459a8665151428aab83bdd1850ff53b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b459a8665151428aab83bdd1850ff53b"}}, "title": "Dietary fat quality impacts genome-wide DNA methylation patterns in a cross-sectional study of Greek preadolescents.", "authors": [{"family": "Voisin", "given": "Sarah", "initials": "S"}, {"family": "Alm\u00e9n", "given": "Markus S", "initials": "MS"}, {"family": "Moschonis", "given": "George", "initials": "G"}, {"family": "Chrousos", "given": "George P", "initials": "GP"}, {"family": "Manios", "given": "Yannis", "initials": "Y"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}], "type": "journal article", "published": "2015-05-00", "journal": {"volume": "23", "issn": "1476-5438", "issue": "5", "pages": "654-662", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "The type and the amount of dietary fat have a significant influence on the metabolic pathways involved in the development of obesity, metabolic syndrome, diabetes type 2 and cardiovascular diseases. However, it is unknown to what extent this modulation is achieved through DNA methylation. We assessed the effects of cholesterol intake, the proportion of energy intake derived from fat, the ratio of polyunsaturated fatty acids (PUFA) to saturated fatty acids (SFA), the ratio of monounsaturated fatty acids (MUFA) to SFA, and the ratio of MUFA+PUFA to SFA on genome-wide DNA methylation patterns in normal-weight and obese children. We determined the genome-wide methylation profile in the blood of 69 Greek preadolescents (\u223c10 years old) as well as their dietary intake for two consecutive weekdays and one weekend day. The methylation levels of one CpG island shore and four sites were significantly correlated with total fat intake. The methylation levels of 2 islands, 11 island shores and 16 sites were significantly correlated with PUFA/SFA; of 9 islands, 26 island shores and 158 sites with MUFA/SFA; and of 10 islands, 40 island shores and 130 sites with (MUFA+PUFA)/SFA. We found significant gene enrichment in 34 pathways for PUFA/SFA, including the leptin pathway, and a significant enrichment in 5 pathways for (MUFA+PUFA)/SFA. Our results suggest that specific changes in DNA methylation may have an important role in the mechanisms involved in the physiological responses to different types of dietary fat.", "doi": "10.1038/ejhg.2014.139", "pmid": "25074463", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg2014139"}, {"db": "pmc", "key": "PMC4402618"}], "notes": [], "created": "2017-05-02T12:58:28.199Z", "modified": "2020-01-21T13:56:04.725Z"}, {"entity": "publication", "iuid": "927e069bd7454856acc9583c56bdef60", "links": {"self": {"href": "https://publications.scilifelab.se/publication/927e069bd7454856acc9583c56bdef60.json"}, "display": {"href": "https://publications.scilifelab.se/publication/927e069bd7454856acc9583c56bdef60"}}, "title": "Evidence for autosomal recessive inheritance in SPG3A caused by homozygosity for a novel ATL1 missense mutation.", "authors": [{"family": "Khan", "given": "Tahir Naeem", "initials": "TN"}, {"family": "Klar", "given": "Joakim", "initials": "J"}, {"family": "Tariq", "given": "Muhammad", "initials": "M"}, {"family": "Anjum Baig", "given": "Shehla", "initials": "S"}, {"family": "Malik", "given": "Naveed Altaf", "initials": "NA"}, {"family": "Yousaf", "given": "Raja", "initials": "R"}, {"family": "Baig", "given": "Shahid Mahmood", "initials": "SM"}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2014-10-00", "journal": {"volume": "22", "issn": "1476-5438", "issue": "10", "pages": "1180-1184", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of disorders characterized by progressive spasticity and weakness of the lower limbs. Autosomal dominant and 'pure' forms of HSP account for \u223c80% of cases in Western societies of whom 10% carry atlastin-1 (ATL1) gene mutations. We report on a large consanguineous family segregating six members with early onset HSP. The pedigree was compatible with both autosomal dominant and autosomal recessive inheritance. Whole-exome sequencing and segregation analysis revealed a homozygous novel missense variant c.353G>A, p.(Arg118Gln) in ATL1 in all six affected family members. Seven heterozygous carriers, five females and two males, showed no clinical signs of HSP with the exception of sub-clinically reduced vibration sensation in one adult female. Our combined findings show that homozygosity for the ATL1 missense variant remains the only plausible cause of HSP, whereas heterozygous carriers are asymptomatic. This apparent autosomal recessive inheritance adds to the clinical complexity of spastic paraplegia 3A and calls for caution using directed genetic screening in HSP.", "doi": "10.1038/ejhg.2014.5", "pmid": "24473461", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg20145"}, {"db": "pmc", "key": "PMC4169543"}], "notes": [], "created": "2017-05-04T14:58:32.962Z", "modified": "2020-01-21T13:56:10.394Z"}, {"entity": "publication", "iuid": "22d0bfd4cf7a4bdfaca700da148cbe5d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/22d0bfd4cf7a4bdfaca700da148cbe5d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/22d0bfd4cf7a4bdfaca700da148cbe5d"}}, "title": "Genes identified in Asian SLE GWASs are also associated with SLE in Caucasian populations.", "authors": [{"family": "Wang", "given": "Chuan", "initials": "C"}, {"family": "Ahlford", "given": "Annika", "initials": "A"}, {"family": "J\u00e4rvinen", "given": "Tiina M", "initials": "TM"}, {"family": "Nordmark", "given": "Gunnel", "initials": "G"}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML"}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E"}, {"family": "Padyukov", "given": "Leonid", "initials": "L"}, {"family": "Sturfelt", "given": "Gunnar", "initials": "G"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "Truedsson", "given": "Lennart", "initials": "L"}, {"family": "Eriksson", "given": "Catharina", "initials": "C"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S"}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C"}, {"family": "Julkunen", "given": "Heikki", "initials": "H"}, {"family": "Criswell", "given": "Lindsey A", "initials": "LA"}, {"family": "Graham", "given": "Robert R", "initials": "RR"}, {"family": "Behrens", "given": "Timothy W", "initials": "TW"}, {"family": "Kere", "given": "Juha", "initials": "J"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK"}], "type": "journal article", "published": "2013-09-00", "journal": {"volume": "21", "issn": "1476-5438", "issue": "9", "pages": "994-999", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Recent genome-wide association studies (GWASs) conducted in Asian populations have identified novel risk loci for systemic lupus erythematosus (SLE). Here, we genotyped 10 single-nucleotide polymorphisms (SNPs) in eight such loci and investigated their disease associations in three independent Caucasian SLE case-control cohorts recruited from Sweden, Finland and the United States. The disease associations of the SNPs in ETS1, IKZF1, LRRC18-WDFY4, RASGRP3, SLC15A4, TNIP1 and 16p11.2 were replicated, whereas no solid evidence of association was observed for the 7q11.23 locus in the Caucasian cohorts. SLC15A4 was significantly associated with renal involvement in SLE. The association of TNIP1 was more pronounced in SLE patients with renal and immunological disorder, which is corroborated by two previous studies in Asian cohorts. The effects of all the associated SNPs, either conferring risk for or being protective against SLE, were in the same direction in Caucasians and Asians. The magnitudes of the allelic effects for most of the SNPs were also comparable across different ethnic groups. On the contrary, remarkable differences in allele frequencies between Caucasian and Asian populations were observed for all associated SNPs. In conclusion, most of the novel SLE risk loci identified by GWASs in Asian populations were also associated with SLE in Caucasian populations. We observed both similarities and differences with respect to the effect sizes and risk allele frequencies across ethnicities.", "doi": "10.1038/ejhg.2012.277", "pmid": "23249952", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "ejhg2012277"}, {"db": "pmc", "key": "PMC3746253"}], "notes": [], "created": "2017-05-04T15:01:17.659Z", "modified": "2021-07-07T15:11:02.329Z"}, {"entity": "publication", "iuid": "7a67f7bf9bdb47b2af025f254c8aa4e3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7a67f7bf9bdb47b2af025f254c8aa4e3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7a67f7bf9bdb47b2af025f254c8aa4e3"}}, "title": "Genome-wide analysis shows association of epigenetic changes in regulators of Rab and Rho GTPases with spinal muscular atrophy severity.", "authors": [{"family": "Zheleznyakova", "given": "Galina Y", "initials": "GY"}, {"family": "Voisin", "given": "Sarah", "initials": "S"}, {"family": "Kiselev", "given": "Anton V", "initials": "AV"}, {"family": "S\u00e4llman Alm\u00e9n", "given": "Markus", "initials": "M"}, {"family": "Xavier", "given": "Miguel J", "initials": "MJ"}, {"family": "Maretina", "given": "Marianna A", "initials": "MA"}, {"family": "Tishchenko", "given": "Lyudmila I", "initials": "LI"}, {"family": "Fredriksson", "given": "Robert", "initials": "R"}, {"family": "Baranov", "given": "Vladislav S", "initials": "VS"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}], "type": "journal article", "published": "2013-09-00", "journal": {"volume": "21", "issn": "1476-5438", "issue": "9", "pages": "988-993", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Spinal muscular atrophy (SMA) is a monogenic disorder that is subdivided into four different types and caused by survival motor neuron gene 1 (SMN1) deletion. Discordant cases of SMA suggest that there exist additional severity modifying factors, apart from the SMN2 gene copy number. Here we performed the first genome-wide methylation profiling of SMA patients and healthy individuals to study the association of DNA methylation status with the severity of the SMA phenotype. We identified strong significant differences in methylation level between SMA patients and healthy controls in CpG sites close to the genes CHML, ARHGAP22, CYTSB, CDK2AP1 and SLC23A2. Interestingly, the CHML and ARHGAP22 genes are associated with the activity of Rab and Rho GTPases, which are important regulators of vesicle formation, actin dynamics, axonogenesis, processes that could be critical for SMA development. We suggest that epigenetic modifications may influence the severity of SMA and that these novel genetic positions could prove to be valuable biomarkers for the understanding of SMA pathogenesis.", "doi": "10.1038/ejhg.2012.293", "pmid": "23299920", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg2012293"}, {"db": "pmc", "key": "PMC3746269"}], "notes": [], "created": "2017-05-04T15:02:23.799Z", "modified": "2020-01-21T13:56:03.175Z"}, {"entity": "publication", "iuid": "0ccfa327678647ed926ff8312b803d72", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0ccfa327678647ed926ff8312b803d72.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0ccfa327678647ed926ff8312b803d72"}}, "title": "Association of TMEM18 variants with BMI and waist circumference in children and correlation of mRNA expression in the PFC with body weight in rats.", "authors": [{"family": "Rask-Andersen", "given": "Mathias", "initials": "M"}, {"family": "Jacobsson", "given": "Josefin A", "initials": "JA"}, {"family": "Moschonis", "given": "George", "initials": "G"}, {"family": "Chavan", "given": "Rohit A", "initials": "RA"}, {"family": "Sikder", "given": "Md Abu Noman", "initials": "MA"}, {"family": "Allz\u00e9n", "given": "Elin", "initials": "E"}, {"family": "Alsi\u00f6", "given": "Johan", "initials": "J"}, {"family": "Chrousos", "given": "George P", "initials": "GP"}, {"family": "Manios", "given": "Yannis", "initials": "Y"}, {"family": "Fredriksson", "given": "Robert", "initials": "R"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}], "type": "journal article", "published": "2012-02-00", "journal": {"volume": "20", "issn": "1476-5438", "issue": "2", "pages": "192-197", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Genome-wide association studies have shown a strong association of single-nucleotide polymorphisms (SNPs) in the near vicinity of the TMEM18 gene. The effects of the TMEM18-associated variants are more readily observed in children. TMEM18 encodes a 3TM protein, which locates to the nuclear membrane. The functional context of TMEM18 and the effects of its associated variants are as of yet undetermined. To further explore the effects of near-TMEM18 variants, we have genotyped two TMEM18-associated SNPs, rs6548238 and rs4854344, in a cohort of 2352 Greek children (Healthy Growth Study). Included in this study are data on anthropomorphic traits body weight, BMI z-score and waist circumference. Also included are dietary energy and macronutrient intake as measured via 24-h recall interviews. Major alleles of rs6548238 and rs4854344 were significantly associated with an increased risk of obesity (odds ratio = 1.489 (1.161-1.910) and 1.494 (1.165-1.917), respectively), and positively correlated to body weight (P = 0.017, P = 0.010) and waist circumference (P = 0.003, P = 0.003). An association to energy and macronutrient intake was not observed in this cohort. We also correlated food intake and body weight in a food choice model in rats to Tmem18 expression in central regions involved in feeding behavior. We observed a strong positive correlation between TMEM18 expression and body weight in the prefrontal cortex (PFC) (r = 0.5694, P = 0.0003) indicating a potential role for TMEM18 in higher functions related to feeding involving the PFC.", "doi": "10.1038/ejhg.2011.176", "pmid": "21952719", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg2011176"}, {"db": "pmc", "key": "PMC3262189"}], "notes": [], "created": "2017-05-04T15:01:56.958Z", "modified": "2020-01-21T13:56:00.670Z"}, {"entity": "publication", "iuid": "675ada456452400aabae4ca754bf7f9b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/675ada456452400aabae4ca754bf7f9b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/675ada456452400aabae4ca754bf7f9b"}}, "title": "Sequencing of high-complexity DNA pools for identification of nucleotide and structural variants in regions associated with complex traits.", "authors": [{"family": "Zaboli", "given": "Ghazal", "initials": "G"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Igl", "given": "Wilmar", "initials": "W"}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Hayward", "given": "Caroline", "initials": "C"}, {"family": "Vitart", "given": "Veronique", "initials": "V"}, {"family": "Campbell", "given": "Susan", "initials": "S"}, {"family": "Zgaga", "given": "Lina", "initials": "L"}, {"family": "Polasek", "given": "Ozren", "initials": "O"}, {"family": "Schmitz", "given": "Gerd", "initials": "G"}, {"family": "van Duijn", "given": "Cornelia", "initials": "C"}, {"family": "Oostra", "given": "Ben", "initials": "B"}, {"family": "Pramstaller", "given": "Peter", "initials": "P"}, {"family": "Hicks", "given": "Andrew", "initials": "A"}, {"family": "Meitinger", "given": "Tomas", "initials": "T"}, {"family": "Rudan", "given": "Igor", "initials": "I"}, {"family": "Wright", "given": "Alan", "initials": "A"}, {"family": "Wilson", "given": "James F", "initials": "JF"}, {"family": "Campbell", "given": "Harry", "initials": "H"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "EUROSPAN Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2012-01-00", "journal": {"volume": "20", "issn": "1476-5438", "issue": "1", "pages": "77-83", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "We have used targeted genomic sequencing of high-complexity DNA pools based on long-range PCR and deep DNA sequencing by the SOLiD technology. The method was used for sequencing of 286 kb from four chromosomal regions with quantitative trait loci (QTL) influencing blood plasma lipid and uric acid levels in DNA pools of 500 individuals from each of five European populations. The method shows very good precision in estimating allele frequencies as compared with individual genotyping of SNPs (r(2) = 0.95, P < 10(-16)). Validation shows that the method is able to identify novel SNPs and estimate their frequency in high-complexity DNA pools. In our five populations, 17% of all SNPs and 61% of structural variants are not available in the public databases. A large fraction of the novel variants show a limited geographic distribution, with 62% of the novel SNPs and 59% of novel structural variants being detected in only one of the populations. The large number of population-specific novel SNPs underscores the need for comprehensive sequencing of local populations in order to identify the causal variants of human traits.", "doi": "10.1038/ejhg.2011.138", "pmid": "21811304", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg2011138"}, {"db": "pmc", "key": "PMC3234506"}], "notes": [], "created": "2017-05-04T14:57:33.963Z", "modified": "2021-07-07T14:37:06.488Z"}, {"entity": "publication", "iuid": "28081e743c0d419d98e741189dd798b0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/28081e743c0d419d98e741189dd798b0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/28081e743c0d419d98e741189dd798b0"}}, "title": "Genomic and clinical characteristics of six patients with partially overlapping interstitial deletions at 10p12p11.", "authors": [{"family": "Wentzel", "given": "Christian", "initials": "C"}, {"family": "Rajcan-Separovic", "given": "Evica", "initials": "E"}, {"family": "Ruivenkamp", "given": "Claudia A L", "initials": "CA"}, {"family": "Chantot-Bastaraud", "given": "Sandra", "initials": "S"}, {"family": "Metay", "given": "Corinne", "initials": "C"}, {"family": "Andrieux", "given": "Joris", "initials": "J"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Gijsbers", "given": "Antoinet C J", "initials": "AC"}, {"family": "Druart", "given": "Luc", "initials": "L"}, {"family": "Hyon", "given": "Capucine", "initials": "C"}, {"family": "Portnoi", "given": "Marie-France", "initials": "MF"}, {"family": "Stattin", "given": "Eva-Lena", "initials": "EL"}, {"family": "Vincent-Delorme", "given": "Catherine", "initials": "C"}, {"family": "Kant", "given": "Sarina G", "initials": "SG"}, {"family": "Steinraths", "given": "Michelle", "initials": "M"}, {"family": "Marlin", "given": "Sandrine", "initials": "S"}, {"family": "Giurgea", "given": "Irina", "initials": "I"}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}], "type": "case reports", "published": "2011-09-00", "journal": {"volume": "19", "issn": "1476-5438", "issue": "9", "pages": "959-964", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "With the clinical implementation of genomic microarrays, the detection of cryptic unbalanced rearrangements in patients with syndromic developmental delay has improved considerably. Here we report the molecular karyotyping and phenotypic description of six new unrelated patients with partially overlapping microdeletions at 10p12.31p11.21 ranging from 1.0 to 10.6\u2009Mb. The smallest region of overlap is 306\u2009kb, which includes WAC gene, known to be associated with microtubule function and to have a role in cell division. Another patient has previously been described with a 10\u2009Mb deletion, partially overlapping with our six patients. All seven patients have developmental delay and a majority of the patients have abnormal behaviour and dysmorphic features, including bulbous nasal tip, deep set eyes, synophrys/thick eyebrows and full cheeks, whereas other features varied. All patients also displayed various visual impairments and six out of seven patients had cardiac malformations. Taken together with the previously reported patient, our study suggests that the detected deletions may represent a new contiguous gene syndrome caused by dosage-sensitive genes that predispose to developmental delay.", "doi": "10.1038/ejhg.2011.71", "pmid": "21522184", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg201171"}, {"db": "pmc", "key": "PMC3179368"}], "notes": [], "created": "2017-05-04T15:01:57.258Z", "modified": "2020-01-21T13:56:01.163Z"}, {"entity": "publication", "iuid": "2ac3ea9b6151417fa83ecfd62869be0e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2ac3ea9b6151417fa83ecfd62869be0e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2ac3ea9b6151417fa83ecfd62869be0e"}}, "title": "Genetic architecture of circulating lipid levels.", "authors": [{"family": "Demirkan", "given": "Ay\u015fe", "initials": "A"}, {"family": "Amin", "given": "Najaf", "initials": "N"}, {"family": "Isaacs", "given": "Aaron", "initials": "A"}, {"family": "Jarvelin", "given": "Marjo-Riitta", "initials": "MR"}, {"family": "Whitfield", "given": "John B", "initials": "JB"}, {"family": "Wichmann", "given": "Heinz-Erich", "initials": "HE"}, {"family": "Kyvik", "given": "Kirsten O H M", "initials": "KO"}, {"family": "Rudan", "given": "Igor", "initials": "I"}, {"family": "Gieger", "given": "Christian", "initials": "C"}, {"family": "Hicks", "given": "Andrew A", "initials": "AA"}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Hottenga", "given": "Jouke-Jan", "initials": "JJ"}, {"family": "Smith", "given": "Johannes J", "initials": "JJ"}, {"family": "Wild", "given": "Sarah H", "initials": "SH"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Willemsen", "given": "Gonneke", "initials": "G"}, {"family": "Mangino", "given": "Massimo", "initials": "M"}, {"family": "Hayward", "given": "Caroline", "initials": "C"}, {"family": "Uitterlinden", "given": "Andr\u00e9 G", "initials": "AG"}, {"family": "Hofman", "given": "Albert", "initials": "A"}, {"family": "Witteman", "given": "Jacqueline", "initials": "J"}, {"family": "Montgomery", "given": "Grant W", "initials": "GW"}, {"family": "Pietil\u00e4inen", "given": "Kirsi H", "initials": "KH"}, {"family": "Rantanen", "given": "Taina", "initials": "T"}, {"family": "Kaprio", "given": "Jaakko", "initials": "J"}, {"family": "D\u00f6ring", "given": "Angela", "initials": "A"}, {"family": "Pramstaller", "given": "Peter P", "initials": "PP"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "de Geus", "given": "Eco J C", "initials": "EJ"}, {"family": "Penninx", "given": "Brenda W", "initials": "BW"}, {"family": "Wilson", "given": "James F", "initials": "JF"}, {"family": "Rivadeneria", "given": "Fernando", "initials": "F"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PK"}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI"}, {"family": "Spector", "given": "Tim", "initials": "T"}, {"family": "Campbell", "given": "Harry", "initials": "H"}, {"family": "Hoehne", "given": "Birgit", "initials": "B"}, {"family": "Martin", "given": "Nicholas G", "initials": "NG"}, {"family": "Oostra", "given": "Ben A", "initials": "BA"}, {"family": "McCarthy", "given": "Mark", "initials": "M"}, {"family": "Peltonen-Palotie", "given": "Leena", "initials": "L"}, {"family": "Aulchenko", "given": "Yurii", "initials": "Y"}, {"family": "Visscher", "given": "Peter M", "initials": "PM"}, {"family": "Ripatti", "given": "Samuli", "initials": "S"}, {"family": "Janssens", "given": "A Cecile J W", "initials": "AC"}, {"family": "van Duijn", "given": "Cornelia M", "initials": "CM"}, {"family": "ENGAGE CONSORTIUM", "given": "", "initials": ""}], "type": "journal article", "published": "2011-07-00", "journal": {"volume": "19", "issn": "1476-5438", "issue": "7", "pages": "813-819", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.", "doi": "10.1038/ejhg.2011.21", "pmid": "21448234", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "ejhg201121"}, {"db": "pmc", "key": "PMC3137496"}], "notes": [], "created": "2017-10-30T13:50:23.175Z", "modified": "2020-01-21T13:56:08.456Z"}, {"entity": "publication", "iuid": "3c311d033f2f4e079d7daf1f85bbb354", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c311d033f2f4e079d7daf1f85bbb354.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c311d033f2f4e079d7daf1f85bbb354"}}, "title": "The 12q14 microdeletion syndrome: six new cases confirming the role of HMGA2 in growth.", "authors": [{"family": "Lynch", "given": "Sally Ann", "initials": "SA"}, {"family": "Foulds", "given": "Nicola", "initials": "N"}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Collins", "given": "Amanda L", "initials": "AL"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Hedberg", "given": "Bernt-Oves", "initials": "BO"}, {"family": "Delaney", "given": "Carol A", "initials": "CA"}, {"family": "Iremonger", "given": "James", "initials": "J"}, {"family": "Murray", "given": "Caroline M", "initials": "CM"}, {"family": "Crolla", "given": "John A", "initials": "JA"}, {"family": "Costigan", "given": "Colm", "initials": "C"}, {"family": "Lam", "given": "Wayne", "initials": "W"}, {"family": "Fitzpatrick", "given": "David R", "initials": "DR"}, {"family": "Regan", "given": "Regina", "initials": "R"}, {"family": "Ennis", "given": "Sean", "initials": "S"}, {"family": "Sharkey", "given": "Freddie", "initials": "F"}], "type": "journal article", "published": "2011-05-00", "journal": {"volume": "19", "issn": "1476-5438", "issue": "5", "pages": "534-539", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and dysmorphism in three diagnostic testing centres, six positive cases yielded a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study, we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions that included HMGA2, and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects, including two with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism.", "doi": "10.1038/ejhg.2010.215", "pmid": "21267005", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg2010215"}, {"db": "pmc", "key": "PMC3083609"}], "notes": [], "created": "2017-05-04T15:01:56.658Z", "modified": "2020-01-21T13:56:01.699Z"}, {"entity": "publication", "iuid": "748a3d45ec0e4674b8121c28a2cb233f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/748a3d45ec0e4674b8121c28a2cb233f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/748a3d45ec0e4674b8121c28a2cb233f"}}, "title": "A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE.", "authors": [{"family": "Sandling", "given": "Johanna K", "initials": "JK"}, {"family": "Garnier", "given": "Sophie", "initials": "S"}, {"family": "Sigurdsson", "given": "Snaevar", "initials": "S"}, {"family": "Wang", "given": "Chuan", "initials": "C"}, {"family": "Nordmark", "given": "Gunnel", "initials": "G"}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E"}, {"family": "Padyukov", "given": "Leonid", "initials": "L"}, {"family": "Sturfelt", "given": "Gunnar", "initials": "G"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "Truedsson", "given": "Lennart", "initials": "L"}, {"family": "Eriksson", "given": "Catharina", "initials": "C"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S"}, {"family": "M\u00e4larstig", "given": "Anders", "initials": "A"}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Criswell", "given": "Lindsey A", "initials": "LA"}, {"family": "Graham", "given": "Robert R", "initials": "RR"}, {"family": "Behrens", "given": "Timothy W", "initials": "TW"}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML"}, {"family": "Alm", "given": "Gunnar", "initials": "G"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}], "type": "journal article", "published": "2011-04-00", "journal": {"volume": "19", "issn": "1476-5438", "issue": "4", "pages": "479-484", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (P(meta)=0.00010 and P(meta)=0.00040, respectively). STAT1 was also associated with SLE in this cohort (P(meta)=3.3 \u00d7 10\u207b\u2075), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis.", "doi": "10.1038/ejhg.2010.197", "pmid": "21179067", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "ejhg2010197"}, {"db": "pmc", "key": "PMC3060320"}], "notes": [], "created": "2017-05-04T15:00:43.036Z", "modified": "2021-07-07T15:11:02.525Z"}], "created": "2017-05-09T09:12:27.445Z", "modified": "2020-11-27T13:14:03.986Z"}