{"entity": "researcher", "timestamp": "2026-07-11T14:55:20.831Z", "family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "affiliations": ["Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, 171 76, Stockholm, Sweden.", "Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.", "Science for Life Laboratory, Karolinska Institutet Science Park, Solna, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6"}}, "publications": [{"entity": "publication", "iuid": "17b67b829187422d82a983585d29be8e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/17b67b829187422d82a983585d29be8e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/17b67b829187422d82a983585d29be8e"}}, "title": "Transposable element insertions in 1000 Swedish individuals.", "authors": [{"family": "Bilgrav Saether", "given": "Kristine", "initials": "K"}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Thonberg", "given": "H\u00e5kan", "initials": "H"}, {"family": "Tham", "given": "Emma", "initials": "E"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications.scilifelab.se/researcher/32a701ee07674785b48b047665e18ee6.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}], "type": "journal article", "published": "2023-07-28", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "18", "issue": "7", "pages": "e0289346", "issn-l": "1932-6203"}, "abstract": "The majority of rare diseases are genetic, and regardless of advanced high-throughput genomics-based investigations, 60% of patients remain undiagnosed. A major factor limiting our ability to identify disease-causing alterations is a poor understanding of the morbid and normal human genome. A major genomic contributor of which function and distribution remain largely unstudied are the transposable elements (TE), which constitute 50% of our genome. Here we aim to resolve this knowledge gap and increase the diagnostic yield of rare disease patients investigated with clinical genome sequencing. To this end we characterized TE insertions in 1000 Swedish individuals from the SweGen dataset and 2504 individuals from the 1000 Genomes Project (1KGP), creating seven population-specific TE insertion databases. Of note, 66% of TE insertions in SweGen were present at >1% in the 1KGP databases, proving that most insertions are common across populations. Focusing on the rare TE insertions, we show that even though ~0.7% of those insertions affect protein coding genes, they rarely affect known disease casing genes (<0.1%). Finally, we applied a TE insertion identification workflow on two clinical cases where disease causing TE insertions were suspected and could verify the presence of pathogenic TE insertions in both. Altogether we demonstrate the importance of TE insertion detection and highlight possible clinical implications in rare disease diagnostics.", "doi": "10.1371/journal.pone.0289346", "pmid": "37506127", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Collaborative", "National Genomics Infrastructure": "Collaborative", "Clinical Genomics Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10381067"}, {"db": "pii", "key": "PONE-D-23-00875"}], "notes": [], "created": "2023-08-15T07:11:25.159Z", "modified": "2024-01-16T13:48:32.834Z"}, {"entity": "publication", "iuid": "e517cf24bfc8442fb1064e821c3b8acf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e517cf24bfc8442fb1064e821c3b8acf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e517cf24bfc8442fb1064e821c3b8acf"}}, "title": "PatientMatcher: A customizable Python-based open-source tool for matching undiagnosed rare disease patients via the Matchmaker Exchange network.", "authors": [{"family": "Rasi", "given": "Chiara", "initials": "C", "orcid": "0000-0002-7001-3988", "researcher": {"href": "https://publications.scilifelab.se/researcher/26beb44f045a442092980ff77b7125e6.json"}}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Magnusson", "given": "M\u00e5ns", "initials": "M", "orcid": "0000-0002-0001-1047", "researcher": {"href": "https://publications.scilifelab.se/researcher/8e75a676a1bf4bfb80cf5ea579b44df0.json"}}, {"family": "Lesko", "given": "Nicole", "initials": "N"}, {"family": "Lagerstedt-Robinson", "given": "Kristina", "initials": "K", "orcid": "0000-0001-9848-0468", "researcher": {"href": "https://publications.scilifelab.se/researcher/63d275105d9b4253944abaa311c986ee.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A", "orcid": "0000-0002-2612-6301", "researcher": {"href": "https://publications.scilifelab.se/researcher/15f660ec95994b6a83d540e48c9b7610.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2022-06-00", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "issn-l": "1059-7794", "volume": "43", "issue": "6", "pages": "708-716"}, "abstract": "The amount of data available from genomic medicine has revolutionized the approach to identify the determinants underlying many rare diseases. The task of confirming a genotype-phenotype causality for a patient affected with a rare genetic disease is often challenging. In this context, the establishment of the Matchmaker Exchange (MME) network has assumed a pivotal role in bridging heterogeneous patient information stored on different medical and research servers. MME has made it possible to solve rare disease cases by \"matching\" the genotypic and phenotypic characteristics of a patient of interest with patient data available at other clinical facilities participating in the network. Here, we present PatientMatcher (https://github.com/Clinical-Genomics/patientMatcher), an open-source Python and MongoDB-based software solution developed by Clinical Genomics facility at the Science for Life Laboratory in Stockholm. PatientMatcher is designed as a standalone MME server, but can easily communicate via REST API with external applications managing genetic analyses and patient data. The MME node is being implemented in clinical routine in collaboration with the Genomic Medicine Center Karolinska at the Karolinska University Hospital. PatientMatcher is written to implement the MME API and provides several customizable settings, including a custom-fit similarity score algorithm and adjustable matching results notifications.", "doi": "10.1002/humu.24358", "pmid": "35192731", "labels": {"Clinical Genomics Stockholm": "Technology development", "Clinical Genomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC9311682"}], "notes": [], "created": "2022-03-07T20:42:34.677Z", "modified": "2022-11-22T07:34:24.825Z"}, {"entity": "publication", "iuid": "87bf78d535ce41dbbf344f9db435066f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/87bf78d535ce41dbbf344f9db435066f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/87bf78d535ce41dbbf344f9db435066f"}}, "title": "Massive parallel sequencing in individuals with multiple primary tumours reveals the benefit of re-analysis.", "authors": [{"family": "Wallander", "given": "Karin", "initials": "K"}, {"family": "Thonberg", "given": "H\u00e5kan", "initials": "H", "orcid": "0000-0003-4503-4717", "researcher": {"href": "https://publications.scilifelab.se/researcher/481958db26a2433ea8d5cc786c3b2bca.json"}}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}], "type": "journal article", "published": "2021-10-28", "journal": {"title": "Hered Cancer Clin Pract", "issn": "1731-2302", "volume": "19", "issue": "1", "pages": "46", "issn-l": null}, "abstract": "Multiple primary cancers, defined as three or more primary tumours, are rare, and there are few genetic studies concerning them. There is a need for increased knowledge on the heritability of multiple primary cancers and genotype-phenotype correlations. We have performed whole-genome/exome sequencing (WGS/WES) in ten individuals with three or more primary tumours, with no previous findings on standard clinical genetic investigations. In one individual with a clinical diagnosis of MEN1, a likely pathogenic cryptic splice site variant was detected in the MEN1 gene. The variant (c.654C > A) is synonymous but we showed in a cDNA analysis that it affects splicing and leads to a frameshift, with the theoretical new amino acid sequence p.(Gly219Glufs*13). In one individual with metachronous colorectal cancers, ovarian cancer, endometrial cancer and chronic lymphocytic leukaemia, we found a likely pathogenic variant in the MLH1 gene (c.27G > A), and two risk factor variants in the genes CHEK2 and HOXB13. The MLH1 variant is synonymous but has previously been shown to be associated to constitutional low-grade hypermethylation of the MLH1 promoter, and segregates with disease in families with colorectal and endometrial cancer. No pathogenic single nucleotide or structural variants were detected in the remaining eight individuals in the study. The pathogenic variants found by WGS/WES were in genes already sequenced by Sanger sequencing and WES in the clinic, without any findings. We conclude that, in individuals with an unequivocal clinical diagnosis of a specific hereditary cancer syndrome, where standard clinical testing failed to detect a causative variant, re-analysis may lead to a diagnosis.", "doi": "10.1186/s13053-021-00203-z", "pmid": "34711244", "labels": {"Clinical Genomics Stockholm": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13053-021-00203-z"}, {"db": "pmc", "key": "PMC8555269"}], "notes": [], "created": "2021-11-20T12:31:14.384Z", "modified": "2024-01-16T13:48:38.170Z"}, {"entity": "publication", "iuid": "3ae89e2aba6e4057b948605c5db0ef47", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3ae89e2aba6e4057b948605c5db0ef47.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3ae89e2aba6e4057b948605c5db0ef47"}}, "title": "Hybrid sequencing resolves two germline ultra-complex chromosomal rearrangements consisting of 137 breakpoint junctions in a single carrier.", "authors": [{"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications.scilifelab.se/researcher/32a701ee07674785b48b047665e18ee6.json"}}, {"family": "Pettersson", "given": "Maria", "initials": "M"}, {"family": "Petri", "given": "Anna", "initials": "A"}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}], "type": "case reports", "published": "2021-05-00", "journal": {"title": "Hum. Genet.", "issn": "1432-1203", "issn-l": "0340-6717", "volume": "140", "issue": "5", "pages": "775-790"}, "abstract": "Chromoanagenesis is a genomic event responsible for the formation of complex structural chromosomal rearrangements (CCRs). Germline chromoanagenesis is rare and the majority of reported cases are associated with an affected phenotype. Here, we report a healthy female carrying two de novo CCRs involving chromosomes 4, 19, 21 and X and chromosomes 7 and 11, respectively, with a total of 137 breakpoint junctions (BPJs). We characterized the CCRs using a hybrid-sequencing approach, combining short-read sequencing, nanopore sequencing, and optical mapping. The results were validated using multiple cytogenetic methods, including fluorescence in situ hybridization, spectral karyotyping, and Sanger sequencing. We identified 137 BPJs, which to our knowledge is the highest number of reported breakpoint junctions in germline chromoanagenesis. We also performed a statistical assessment of the positioning of the breakpoints, revealing a significant enrichment of BPJ-affecting genes (96 intragenic BPJs, 26 genes, p < 0.0001), indicating that the CCRs formed during active transcription of these genes. In addition, we find that the DNA fragments are unevenly and non-randomly distributed across the derivative chromosomes indicating a multistep process of scattering and re-joining of DNA fragments. In summary, we report a new maximum number of BPJs (137) in germline chromoanagenesis. We also show that a hybrid sequencing approach is necessary for the correct characterization of complex CCRs. Through in-depth statistical assessment, it was found that the CCRs most likely was formed through an event resembling chromoplexy-a catastrophic event caused by erroneous transcription factor binding.", "doi": "10.1007/s00439-020-02242-3", "pmid": "33315133", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Long read": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s00439-020-02242-3"}, {"db": "pmc", "key": "PMC8052244"}], "notes": [], "created": "2021-01-08T16:30:24.743Z", "modified": "2024-01-16T13:48:39.901Z"}, {"entity": "publication", "iuid": "804fe367d4ba45b59d3d3ed95177e766", "links": {"self": {"href": "https://publications.scilifelab.se/publication/804fe367d4ba45b59d3d3ed95177e766.json"}, "display": {"href": "https://publications.scilifelab.se/publication/804fe367d4ba45b59d3d3ed95177e766"}}, "title": "Overexpression of chromatin remodeling and tyrosine kinase genes in iAMP21-positive acute lymphoblastic leukemia.", "authors": [{"family": "Ivanov \u00d6fverholm", "given": "Ingegerd", "initials": "I", "orcid": "0000-0002-6907-8004", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ba94eeea4d24e9c8c354fe1256fd0ce.json"}}, {"family": "Zachariadis", "given": "Vasilios", "initials": "V", "orcid": "0000-0001-9360-9859", "researcher": {"href": "https://publications.scilifelab.se/researcher/0607f2b65c12492cb30fb7a445d37937.json"}}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Marincevic-Zuniga", "given": "Yanara", "initials": "Y", "orcid": "0000-0001-5576-2115", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb045b70f16140b6b6e69476d701012c.json"}}, {"family": "Tran", "given": "Anh Nhi", "initials": "AN"}, {"family": "Saft", "given": "Leonie", "initials": "L"}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "L\u00f6nnerholm", "given": "Gudmar", "initials": "G"}, {"family": "Harila-Saari", "given": "Arja", "initials": "A"}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M", "orcid": "0000-0002-4974-425X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9f9dec008f1b42868dd133e9a396c968.json"}}, {"family": "Heyman", "given": "Mats", "initials": "M"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Barbany", "given": "Gisela", "initials": "G"}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Leuk. Lymphoma", "issn": "1029-2403", "issn-l": "1026-8022", "volume": "61", "issue": "3", "pages": "604-613"}, "abstract": "Intrachromosomal amplification of chromosome 21 (iAMP21) is a cytogenetic subtype associated with relapse and poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). The biology behind the high relapse risk is unknown and the aim of this study was to further characterize the genomic and transcriptional landscape of iAMP21. Using DNA arrays and sequencing, we could identify rearrangements and aberrations characteristic for iAMP21. RNA sequencing revealed that only half of the genes in the minimal region of amplification (20/45) were differentially expressed in iAMP21. Among them were the top overexpressed genes (p < 0.001) in iAMP21 vs. BCP ALL without iAMP21 and three candidate genes could be identified, the tyrosine kinase gene DYRK1A and chromatin remodeling genes CHAF1B and SON. While overexpression of DYRK1A and CHAF1B is associated with poor prognosis in malignant diseases including myeloid leukemia, this is the first study to show significant correlation with iAMP21-positive ALL.", "doi": "10.1080/10428194.2019.1678153", "pmid": "31640433", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2019-12-03T10:45:21.445Z", "modified": "2024-01-16T13:48:42.841Z"}, {"entity": "publication", "iuid": "b113002942174b6b8c2f67907d1d2182", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b113002942174b6b8c2f67907d1d2182.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b113002942174b6b8c2f67907d1d2182"}}, "title": "Discovery of Novel Sequences in 1,000 Swedish Genomes.", "authors": [{"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications.scilifelab.se/researcher/32a701ee07674785b48b047665e18ee6.json"}}, {"family": "M\u00e5rtensson", "given": "Gustaf", "initials": "G"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}], "type": "journal article", "published": "2020-01-01", "journal": {"volume": "37", "issn": "1537-1719", "issue": "1", "pages": "18-30", "title": "Mol. Biol. Evol.", "issn-l": "0737-4038"}, "abstract": "Novel sequences (NSs), not present in the human reference genome, are abundant and remain largely unexplored. Here, we utilize de novo assembly to study NS in 1,000 Swedish individuals first sequenced as part of the SweGen project revealing a total of 46 Mb in 61,044 distinct contigs of sequences not present in GRCh38. The contigs were aligned to recently published catalogs of Icelandic and Pan-African NSs, as well as the chimpanzee genome, revealing a great diversity of shared sequences. Analyzing the positioning of NS across the chimpanzee genome, we find that 2,807 NS align confidently within 143 chimpanzee orthologs of human genes. Aligning the whole genome sequencing data to the chimpanzee genome, we discover ancestral NS common throughout the Swedish population. The NSs were searched for repeats and repeat elements: revealing a majority of repetitive sequence (56%), and enrichment of simple repeats (28%) and satellites (15%). Lastly, we align the unmappable reads of a subset of the thousand genomes data to our collection of NS, as well as the previously published Pan-African NS: revealing that both the Swedish and Pan-African NS are widespread, and that the Swedish NSs are largely a subset of the Pan-African NS. Overall, these results highlight the importance of creating a more diverse reference genome and illustrate that significant amounts of the NS may be of ancestral origin.", "doi": "10.1093/molbev/msz176", "pmid": "31560401", "labels": {"NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5555682"}, {"db": "pmc", "key": "PMC6984370"}], "notes": [], "created": "2019-10-30T08:45:30.942Z", "modified": "2024-01-16T13:48:43.107Z"}, {"entity": "publication", "iuid": "f754205bb071486683b1bde1528c6303", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f754205bb071486683b1bde1528c6303.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f754205bb071486683b1bde1528c6303"}}, "title": "Comprehensive structural variation genome map of individuals carrying complex chromosomal rearrangements.", "authors": [{"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Pettersson", "given": "Maria", "initials": "M", "orcid": "0000-0003-3120-1625", "researcher": {"href": "https://publications.scilifelab.se/researcher/bfdfac2208ce4d1a877fa4957e2f4ea4.json"}}, {"family": "Vezzi", "given": "Francesco", "initials": "F", "orcid": "0000-0002-0243-0018", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e630602a0a449e899701c781ee59fb6.json"}}, {"family": "Wincent", "given": "Josephine", "initials": "J"}, {"family": "K\u00e4ller", "given": "Max", "initials": "M", "orcid": "0000-0001-6813-3051", "researcher": {"href": "https://publications.scilifelab.se/researcher/536ad902a272482aba853c078557e240.json"}}, {"family": "Gruselius", "given": "Joel", "initials": "J"}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Syk Lundberg", "given": "Elisabeth", "initials": "E"}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB", "orcid": "0000-0002-2090-298X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a1a6b6936aa442384c5aef0eff0715a.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}], "type": "journal article", "published": "2019-02-00", "journal": {"volume": "15", "issn": "1553-7404", "issue": "2", "pages": "e1007858", "title": "PLoS Genet.", "issn-l": "1553-7390"}, "abstract": "Complex chromosomal rearrangements (CCRs) are rearrangements involving more than two chromosomes or more than two breakpoints. Whole genome sequencing (WGS) allows for outstanding high resolution characterization on the nucleotide level in unique sequences of such rearrangements, but problems remain for mapping breakpoints in repetitive regions of the genome, which are known to be prone to rearrangements. Hence, multiple complementary WGS experiments are sometimes needed to solve the structures of CCRs. We have studied three individuals with CCRs: Case 1 and Case 2 presented with de novo karyotypically balanced, complex interchromosomal rearrangements (46,XX,t(2;8;15)(q35;q24.1;q22) and 46,XY,t(1;10;5)(q32;p12;q31)), and Case 3 presented with a de novo, extremely complex intrachromosomal rearrangement on chromosome 1. Molecular cytogenetic investigation revealed cryptic deletions in the breakpoints of chromosome 2 and 8 in Case 1, and on chromosome 10 in Case 2, explaining their clinical symptoms. In Case 3, 26 breakpoints were identified using WGS, disrupting five known disease genes. All rearrangements were subsequently analyzed using optical maps, linked-read WGS, and short-read WGS. In conclusion, we present a case series of three unique de novo CCRs where we by combining the results from the different technologies fully solved the structure of each rearrangement. The power in combining short-read WGS with long-molecule sequencing or optical mapping in these unique de novo CCRs in a clinical setting is demonstrated.", "doi": "10.1371/journal.pgen.1007858", "pmid": "30735495", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Clinical Genomics Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-18-00854"}, {"db": "pmc", "key": "PMC6368290"}], "notes": [], "created": "2019-11-25T10:49:59.013Z", "modified": "2024-01-16T13:48:44.771Z"}, {"entity": "publication", "iuid": "51df1c5fe3f94631a980b3a69ab8490c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/51df1c5fe3f94631a980b3a69ab8490c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/51df1c5fe3f94631a980b3a69ab8490c"}}, "title": "Replicative and non-replicative mechanisms in the formation of clustered CNVs are indicated by whole genome characterization.", "authors": [{"family": "Nazaryan-Petersen", "given": "Lusine", "initials": "L"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications.scilifelab.se/researcher/32a701ee07674785b48b047665e18ee6.json"}}, {"family": "Pettersson", "given": "Maria", "initials": "M", "orcid": "0000-0003-3120-1625", "researcher": {"href": "https://publications.scilifelab.se/researcher/bfdfac2208ce4d1a877fa4957e2f4ea4.json"}}, {"family": "Lundin", "given": "Johanna", "initials": "J"}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Wincent", "given": "Josephine", "initials": "J"}, {"family": "Lieden", "given": "Agne", "initials": "A"}, {"family": "Lovmar", "given": "Lovisa", "initials": "L"}, {"family": "Ottosson", "given": "Jesper", "initials": "J"}, {"family": "Gacic", "given": "Jelena", "initials": "J", "orcid": "0000-0002-1431-7792", "researcher": {"href": "https://publications.scilifelab.se/researcher/a2a1747f125144b48815d5793ac1bc13.json"}}, {"family": "M\u00e4kitie", "given": "Outi", "initials": "O", "orcid": "0000-0002-4547-001X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce0614bdc717455b9af64a05ab4aa4aa.json"}}, {"family": "Nordgren", "given": "Ann", "initials": "A"}, {"family": "Vezzi", "given": "Francesco", "initials": "F"}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "K\u00e4ller", "given": "Max", "initials": "M", "orcid": "0000-0001-6813-3051", "researcher": {"href": "https://publications.scilifelab.se/researcher/536ad902a272482aba853c078557e240.json"}}, {"family": "Hjortsh\u00f8j", "given": "Tina Duelund", "initials": "TD"}, {"family": "Jespersgaard", "given": "Cathrine", "initials": "C"}, {"family": "Houssari", "given": "Rayan", "initials": "R"}, {"family": "Pignata", "given": "Laura", "initials": "L"}, {"family": "Bak", "given": "Mads", "initials": "M"}, {"family": "Tommerup", "given": "Niels", "initials": "N", "orcid": "0000-0003-2304-0112", "researcher": {"href": "https://publications.scilifelab.se/researcher/d163b474ab954465b310cc47ac7403eb.json"}}, {"family": "Lundberg", "given": "Elisabeth Syk", "initials": "ES", "orcid": "0000-0001-5692-725X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f23c7a2e475443ef9fdbbd7b46c9991e.json"}}, {"family": "T\u00fcmer", "given": "Zeynep", "initials": "Z"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}], "type": "journal article", "published": "2018-11-00", "journal": {"volume": "14", "issn": "1553-7404", "issue": "11", "pages": "e1007780", "title": "PLoS Genet.", "issn-l": "1553-7390"}, "abstract": "Clustered copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) are often reported as germline chromothripsis. However, such cases might need further investigations by massive parallel whole genome sequencing (WGS) in order to accurately define the underlying complex rearrangement, predict the occurrence mechanisms and identify additional complexities. Here, we utilized WGS to delineate the rearrangement structure of 21 clustered CNV carriers first investigated by CMA and identified a total of 83 breakpoint junctions (BPJs). The rearrangements were further sub-classified depending on the patterns observed: I) Cases with only deletions (n = 8) often had additional structural rearrangements, such as insertions and inversions typical to chromothripsis; II) cases with only duplications (n = 7) or III) combinations of deletions and duplications (n = 6) demonstrated mostly interspersed duplications and BPJs enriched with microhomology. In two cases the rearrangement mutational signatures indicated both a breakage-fusion-bridge cycle process and haltered formation of a ring chromosome. Finally, we observed two cases with Alu- and LINE-mediated rearrangements as well as two unrelated individuals with seemingly identical clustered CNVs on 2p25.3, possibly a rare European founder rearrangement. In conclusion, through detailed characterization of the derivative chromosomes we show that multiple mechanisms are likely involved in the formation of clustered CNVs and add further evidence for chromoanagenesis mechanisms in both \"simple\" and highly complex chromosomal rearrangements. Finally, WGS characterization adds positional information, important for a correct clinical interpretation and deciphering mechanisms involved in the formation of these rearrangements.", "doi": "10.1371/journal.pgen.1007780", "pmid": "30419018", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-18-01290"}, {"db": "pmc", "key": "PMC6258378"}], "notes": [], "created": "2019-01-04T14:04:10.399Z", "modified": "2021-07-07T15:19:21.415Z"}]}