{"entity": "researcher", "timestamp": "2026-08-10T20:44:07.856Z", "family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "affiliations": ["Department of Immunology, Genetics and Pathology, Science for Life Laboratory Uppsala, Uppsala University, Uppsala, Sweden. Lars.Feuk@igp.uu.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4"}}, "publications": [{"entity": "publication", "iuid": "e081c532d4de40fea93e6cad64023850", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e081c532d4de40fea93e6cad64023850.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e081c532d4de40fea93e6cad64023850"}}, "title": "Nationwide multicentre study of Nanopore long-read sequencing for 16S rRNA-species identification.", "authors": [{"family": "Brunet", "given": "Sofia", "initials": "S"}, {"family": "Grankvist", "given": "Anna", "initials": "A"}, {"family": "Jaen-Luchoro", "given": "Daniel", "initials": "D", "orcid": "0000-0002-5988-6227", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a821a703a144b5aa5a783e7f8043d86.json"}}, {"family": "Bergdahl", "given": "Maria", "initials": "M"}, {"family": "Tison", "given": "Jean-Luc", "initials": "JL"}, {"family": "Wester", "given": "Annica", "initials": "A"}, {"family": "Elfving", "given": "Karin", "initials": "K"}, {"family": "Brandenburg", "given": "Jule", "initials": "J"}, {"family": "Gullsby", "given": "Karolina", "initials": "K"}, {"family": "Lindsten", "given": "Christoffer", "initials": "C"}, {"family": "Arvidsson", "given": "Lars-Ola", "initials": "LO"}, {"family": "Larsson", "given": "Helena", "initials": "H", "orcid": "0000-0002-6851-3297", "researcher": {"href": "https://publications.scilifelab.se/researcher/21f2cca2f6b74c5393c0fc33bcf15ee6.json"}}, {"family": "Eilers", "given": "Hinnerk", "initials": "H"}, {"family": "Strand", "given": "Anna S\u00f6derlund", "initials": "AS"}, {"family": "Lannefors", "given": "Mimi", "initials": "M"}, {"family": "Keskitalo", "given": "Johanna", "initials": "J"}, {"family": "Rylander", "given": "Felicia", "initials": "F"}, {"family": "Welander", "given": "Jenny", "initials": "J"}, {"family": "Jungestrom", "given": "Malin Bergman", "initials": "MB"}, {"family": "Ge\u00f6rg", "given": "Miriam", "initials": "M"}, {"family": "Kaden", "given": "Rene", "initials": "R", "orcid": "0000-0002-2111-9751", "researcher": {"href": "https://publications.scilifelab.se/researcher/018870b1d0034ee09552a3ae451d5504.json"}}, {"family": "Karlsson", "given": "Ida", "initials": "I"}, {"family": "Linde", "given": "Anna-Malin", "initials": "AM"}, {"family": "Mernelius", "given": "Sara", "initials": "S"}, {"family": "Berglind", "given": "Linda", "initials": "L"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Kerje", "given": "Susanne", "initials": "S", "orcid": "0000-0002-2944-9288", "researcher": {"href": "https://publications.scilifelab.se/researcher/078ca525f2cc4a68a430f2655e45efce.json"}}, {"family": "Karlsson", "given": "Linda", "initials": "L", "orcid": "0000-0003-2704-1788", "researcher": {"href": "https://publications.scilifelab.se/researcher/9942f9d57c094401a1bb9b965f300092.json"}}, {"family": "Sj\u00f6din", "given": "Andreas", "initials": "A", "orcid": "0000-0001-5350-4219", "researcher": {"href": "https://publications.scilifelab.se/researcher/6398d7c06a414ea6bcaf2579a8587452.json"}}, {"family": "Guerra-Blomqvist", "given": "Lina", "initials": "L"}, {"family": "Wallin", "given": "Frans", "initials": "F"}, {"family": "Fagerstr\u00f6m", "given": "Anna", "initials": "A", "orcid": "0000-0002-6276-8811", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8dc177a668c4256be2893eb98abddd4.json"}}, {"family": "Vondracek", "given": "Martin", "initials": "M"}, {"family": "M\u00f6lling", "given": "Paula", "initials": "P"}, {"family": "Hallb\u00e4ck", "given": "Erika T\u00e5ng", "initials": "ET"}], "type": "journal article", "published": "2025-08-00", "journal": {"title": "Eur. J. Clin. Microbiol. Infect. Dis.", "issn": "1435-4373", "volume": "44", "issue": "8", "pages": "1907-1916", "issn-l": "0934-9723"}, "abstract": "Recent improvements in Nanopore sequencing chemistry has made it a promising platform for long-read 16S rRNA sequencing. This study evaluated its clinical utility in a nationwide collaboration coordinated by Genomic Medicine Sweden.\n\nThirteen mock samples comprised of various bacterial strains and an External Quality Assessment (EQA) panel from QCMD (Quality Control for Molecular Diagnostics) were analysed by 20 microbiological laboratories across Sweden, using the recent v14 chemistry. Most laboratories generated full-length 16S rRNA sequencing libraries using an optimized protocol for the 16S Barcoding Kit 24, while two laboratories employed in-house PCR coupled with the Ligation Sequencing Kit. The commercial 16S bioinformatic pipeline from 1928 Diagnostics (1928-16S) was evaluated and compared with the open-sourced gms_16S pipeline that is based on the EMU classification tool (GMS-16S).\n\nSeventeen out of 20 laboratories successfully sequenced and analysed the samples. Laboratories that used sodium acetate-containing elution buffers faced compatibility issues during library construction, resulting in reduced read count. High bacterial load samples were generally well-characterized, whereas hard-to-lyse bacteria such as Gram-positive strains were detected at lower abundance. The GMS-16S tool provided improved species-level identification compared to the 1928-16S pipeline, particularly for closely related taxa within the Streptococcus and Staphylococcus genera.\n\nNanopore sequencing demonstrated promising potential for bacterial identification in a clinical setting. The results prompt further optimization of the protocol to improve detection of a broader range of species. This multicentre study highlights the feasibility of implementing Nanopore sequencing into clinical microbiological laboratories, for improved national precision diagnostics.", "doi": "10.1007/s10096-025-05158-w", "pmid": "40348924", "labels": {"Clinical Genomics": "Collaborative", "Clinical Genomics Gothenburg": "Service", "National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Long read": "Collaborative", "Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics Uppsala": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12321653"}, {"db": "pii", "key": "10.1007/s10096-025-05158-w"}], "notes": [], "created": "2025-07-08T13:51:52.338Z", "modified": "2025-11-26T14:14:27.926Z"}, {"entity": "publication", "iuid": "468568bfcb944c3089c1cc62240911bb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/468568bfcb944c3089c1cc62240911bb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/468568bfcb944c3089c1cc62240911bb"}}, "title": "Resolving complex duplication variants in autism spectrum disorder using long-read genome sequencing.", "authors": [{"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications.scilifelab.se/researcher/32a701ee07674785b48b047665e18ee6.json"}}, {"family": "Higginbotham", "given": "Edward J", "initials": "EJ"}, {"family": "Lenner", "given": "Felix", "initials": "F"}, {"family": "Howe", "given": "Jennifer", "initials": "J"}, {"family": "Fernandez", "given": "Bridget A", "initials": "BA"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Scherer", "given": "Stephen W", "initials": "SW"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2024-11-20", "journal": {"title": "Genome Res.", "issn": "1549-5469", "volume": "34", "issue": "11", "pages": "1763-1773", "issn-l": "1088-9051"}, "abstract": "Rare or de novo structural variation, primarily in the form of copy number variants, is detected in 5%-10% of autism spectrum disorder (ASD) families. While complex structural variants involving duplications can generally be detected using microarray or short-read genome sequencing (GS), these methods frequently fail to characterize breakpoints at nucleotide resolution, requiring additional molecular methods for validation and fine-mapping. Here, we use Oxford Nanopore Technologies PromethION long-read GS to characterize complex genomic rearrangements (CGRs) involving large duplications that segregate with ASD in five families. In total, we investigated 13 CGR carriers and were able to resolve all breakpoint junctions at nucleotide resolution. While all breakpoints were identified, the precise genomic architecture of one rearrangement remained unresolved with three different potential structures. The findings in two families include potential fusion genes formed through duplication rearrangements, involving IL1RAPL1-DMD and SUPT16H-CHD8 In two of the families originating from the same geographical region, an identical rearrangement involving ANK2 was identified, which likely represents a founder variant. In addition, we analyze methylation status directly from the long-read data, allowing us to assess the activity of rearranged genes and regulatory regions. Investigation of methylation across the CGRs reveals aberrant methylation status in carriers across a rearrangement affecting the CREBBP locus. In aggregate, our results demonstrate the utility of nanopore sequencing to pinpoint CGRs associated with ASD in five unrelated families, and highlight the importance of a gene-centric description of disease-associated complex chromosomal rearrangements.", "doi": "10.1101/gr.279263.124", "pmid": "39472019", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Long read": "Collaborative", "National Genomics Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11610597"}, {"db": "pii", "key": "gr.279263.124"}, {"db": "medline", "key": "9509184"}], "notes": [], "created": "2024-11-04T20:46:38.030Z", "modified": "2025-11-18T20:50:04.852Z"}, {"entity": "publication", "iuid": "92996e534bd244ad802a06aba40392a9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/92996e534bd244ad802a06aba40392a9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/92996e534bd244ad802a06aba40392a9"}}, "title": "A multiomic characterization of the leukemia cell line REH using short- and long-read sequencing.", "authors": [{"family": "Lysenkova Wiklander", "given": "Mariya", "initials": "M", "orcid": "0000-0002-0012-2310", "researcher": {"href": "https://publications.scilifelab.se/researcher/48850e5606b9470caa6b130286055388.json"}}, {"family": "Arvidsson", "given": "Gustav", "initials": "G", "orcid": "0000-0001-7396-1820", "researcher": {"href": "https://publications.scilifelab.se/researcher/29beb4f9dd8b460382eab4f916fc1072.json"}}, {"family": "Bunikis", "given": "Ignas", "initials": "I", "orcid": "0009-0008-8375-0451", "researcher": {"href": "https://publications.scilifelab.se/researcher/d2a9c139b7d64681a5712250d3cf63ff.json"}}, {"family": "Lundmark", "given": "Anders", "initials": "A"}, {"family": "Raine", "given": "Amanda", "initials": "A", "orcid": "0000-0002-2775-6516", "researcher": {"href": "https://publications.scilifelab.se/researcher/a97b7df8379f42f0a412fb7c234a6c70.json"}}, {"family": "Marincevic-Zuniga", "given": "Yanara", "initials": "Y", "orcid": "0000-0001-5576-2115", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb045b70f16140b6b6e69476d701012c.json"}}, {"family": "Gezelius", "given": "Henrik", "initials": "H", "orcid": "0000-0002-6242-6344", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ad329767af94f9f9ad2c96771ff01d9.json"}}, {"family": "Bremer", "given": "Anna", "initials": "A"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}], "type": "journal article", "published": "2024-08-00", "journal": {"title": "Life Sci. Alliance", "issn": "2575-1077", "issn-l": "2575-1077", "volume": "7", "issue": "8", "pages": null}, "abstract": "The B-cell acute lymphoblastic leukemia (ALL) cell line REH, with the t(12;21) ETV6::RUNX1 translocation, is known to have a complex karyotype defined by a series of large-scale chromosomal rearrangements. Taken from a 15-yr-old at relapse, the cell line offers a practical model for the study of pediatric B-ALL. In recent years, short- and long-read DNA and RNA sequencing have emerged as a complement to karyotyping techniques in the resolution of structural variants in an oncological context. Here, we explore the integration of long-read PacBio and Oxford Nanopore whole-genome sequencing, IsoSeq RNA sequencing, and short-read Illumina sequencing to create a detailed genomic and transcriptomic characterization of the REH cell line. Whole-genome sequencing clarified the molecular traits of disrupted ALL-associated genes including CDKN2A, PAX5, BTG1, VPREB1, and TBL1XR1, as well as the glucocorticoid receptor NR3C1 Meanwhile, transcriptome sequencing identified seven fusion genes within the genomic breakpoints. Together, our extensive whole-genome investigation makes high-quality open-source data available to the leukemia genomics community.", "doi": "10.26508/lsa.202302481", "pmid": "38777370", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Long read": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "NGI Short read": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11111970"}, {"db": "pii", "key": "7/8/e202302481"}], "notes": [], "created": "2024-08-02T11:59:07.510Z", "modified": "2025-02-28T14:23:51.125Z"}, {"entity": "publication", "iuid": "b6d7787be6f54069811e84189b52b7ab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b6d7787be6f54069811e84189b52b7ab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b6d7787be6f54069811e84189b52b7ab"}}, "title": "Long-read whole-genome analysis of human single cells.", "authors": [{"family": "H\u00e5rd", "given": "Joanna", "initials": "J"}, {"family": "Mold", "given": "Jeff E", "initials": "JE"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Tellgren-Roth", "given": "Christian", "initials": "C", "orcid": "0000-0003-0502-3693", "researcher": {"href": "https://publications.scilifelab.se/researcher/982873aade554b38b26b877298db5115.json"}}, {"family": "H\u00e4ggqvist", "given": "Susana", "initials": "S"}, {"family": "Bunikis", "given": "Ignas", "initials": "I"}, {"family": "Contreras-Lopez", "given": "Orlando", "initials": "O"}, {"family": "Chin", "given": "Chen-Shan", "initials": "CS", "orcid": "0000-0003-4394-2455", "researcher": {"href": "https://publications.scilifelab.se/researcher/58952eb371364939acef96efba96a143.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Rubin", "given": "Carl-Johan", "initials": "CJ", "orcid": "0000-0001-8238-5052", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bd98ada4083444e8336ef3ec53df488.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Micha\u00eblsson", "given": "Jakob", "initials": "J"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}], "type": "journal article", "published": "2023-08-24", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "14", "issue": "1", "pages": "5164"}, "abstract": "Long-read sequencing has dramatically increased our understanding of human genome variation. Here, we demonstrate that long-read technology can give new insights into the genomic architecture of individual cells. Clonally expanded CD8+ T-cells from a human donor were subjected to droplet-based multiple displacement amplification (dMDA) to generate long molecules with reduced bias. PacBio sequencing generated up to 40% genome coverage per single-cell, enabling detection of single nucleotide variants (SNVs), structural variants (SVs), and tandem repeats, also in regions inaccessible by short reads. 28 somatic SNVs were detected, including one case of mitochondrial heteroplasmy. 5473 high-confidence SVs/cell were discovered, a sixteen-fold increase compared to Illumina-based results from clonally related cells. Single-cell de novo assembly generated a genome size of up to 598 Mb and 1762 (12.8%) complete gene models. In summary, our work shows the promise of long-read sequencing toward characterization of the full spectrum of genetic variation in single cells.", "doi": "10.1038/s41467-023-40898-3", "pmid": "37620373", "labels": {"National Genomics Infrastructure": "Technology development", "NGI Uppsala (Uppsala Genome Center)": "Technology development", "NGI Stockholm (Genomics Applications)": "Collaborative", "NGI Long read": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "NGI Single cell": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC10449900"}, {"db": "pii", "key": "10.1038/s41467-023-40898-3"}], "notes": [], "created": "2023-09-04T11:21:18.412Z", "modified": "2024-11-25T10:15:50.528Z"}, {"entity": "publication", "iuid": "7feac7b384bd4538b6116d30a4f37f9d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7feac7b384bd4538b6116d30a4f37f9d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7feac7b384bd4538b6116d30a4f37f9d"}}, "title": "CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations.", "authors": [{"family": "H\u00f6ijer", "given": "Ida", "initials": "I", "orcid": "0000-0002-3915-3384", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba4ce20b1b447ada4fdc8256211436e.json"}}, {"family": "Emmanouilidou", "given": "Anastasia", "initials": "A"}, {"family": "\u00d6stlund", "given": "Rebecka", "initials": "R", "orcid": "0000-0003-4460-7245", "researcher": {"href": "https://publications.scilifelab.se/researcher/03b1d5938f74406ebffb5b49ba5b182c.json"}}, {"family": "van Schendel", "given": "Robin", "initials": "R", "orcid": "0000-0001-7068-0679", "researcher": {"href": "https://publications.scilifelab.se/researcher/6aa5a36e5b534bab8a04b4c8f040abb4.json"}}, {"family": "Bozorgpana", "given": "Selma", "initials": "S"}, {"family": "Tijsterman", "given": "Marcel", "initials": "M", "orcid": "0000-0001-8465-9002", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1e816845f6048e2a2c7dc29e9a13cdf.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U", "orcid": "0000-0002-6316-3355", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8739f0f42c44019ab88a49db350a4f2.json"}}, {"family": "den Hoed", "given": "Marcel", "initials": "M", "orcid": "0000-0001-8081-428X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d712cc087d344b15ab9a7971640acebe.json"}}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}], "type": "journal article", "published": "2022-02-02", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "13", "issue": "1", "pages": "627"}, "abstract": "CRISPR-Cas9 genome editing has potential to cure diseases without current treatments, but therapies must be safe. Here we show that CRISPR-Cas9 editing can introduce unintended mutations in vivo, which are passed on to the next generation. By editing fertilized zebrafish eggs using four guide RNAs selected for off-target activity in vitro, followed by long-read sequencing of DNA from >1100 larvae, juvenile and adult fish across two generations, we find that structural variants (SVs), i.e., insertions and deletions \u226550 bp, represent 6% of editing outcomes in founder larvae. These SVs occur both at on-target and off-target sites. Our results also illustrate that adult founder zebrafish are mosaic in their germ cells, and that 26% of their offspring carries an off-target mutation and 9% an SV. Hence, pre-testing for off-target activity and SVs using patient material is advisable in clinical applications, to reduce the risk of unanticipated effects with potentially large implications.", "doi": "10.1038/s41467-022-28244-5", "pmid": "35110541", "labels": {"National Genomics Infrastructure": "Technology development", "NGI Uppsala (Uppsala Genome Center)": "Technology development", "NGI Long read": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8810904"}, {"db": "pii", "key": "10.1038/s41467-022-28244-5"}], "notes": [], "created": "2022-02-17T14:45:40.515Z", "modified": "2024-01-16T13:48:37.595Z"}, {"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": "5c5a5f2b09394d1bb33632eb074d5aaa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5c5a5f2b09394d1bb33632eb074d5aaa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5c5a5f2b09394d1bb33632eb074d5aaa"}}, "title": "Characterization of the nuclear and cytosolic transcriptomes in human brain tissue reveals new insights into the subcellular distribution of RNA transcripts.", "authors": [{"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Niazi", "given": "Adnan", "initials": "A"}, {"family": "Bj\u00f6rklund", "given": "\u00c5sa K", "initials": "\u00c5K"}, {"family": "Westholm", "given": "Jakub Orzechowski", "initials": "JO"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2021-02-18", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "11", "issue": "1", "pages": "4076", "issn-l": "2045-2322"}, "abstract": "Transcriptome analysis has mainly relied on analyzing RNA sequencing data from whole cells, overlooking the impact of subcellular RNA localization and its influence on our understanding of gene function, and interpretation of gene expression signatures in cells. Here, we separated cytosolic and nuclear RNA from human fetal and adult brain samples and performed a comprehensive analysis of cytosolic and nuclear transcriptomes. There are significant differences in RNA expression for protein-coding and lncRNA genes between cytosol and nucleus. We show that transcripts encoding the nuclear-encoded mitochondrial proteins are significantly enriched in the cytosol compared to the rest of protein-coding genes. Differential expression analysis between fetal and adult frontal cortex show that results obtained from the cytosolic RNA differ from results using nuclear RNA both at the level of transcript types and the number of differentially expressed genes. Our data provide a resource for the subcellular localization of thousands of RNA transcripts in the human brain and highlight differences in using the cytosolic or the nuclear transcriptomes for expression analysis.", "doi": "10.1038/s41598-021-83541-1", "pmid": "33603054", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-021-83541-1"}, {"db": "pmc", "key": "PMC7893067"}], "notes": [], "created": "2021-02-23T09:14:46.854Z", "modified": "2024-01-16T13:48:40.658Z"}, {"entity": "publication", "iuid": "5660b7d3ef2044dca8d30c36ddc899a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5660b7d3ef2044dca8d30c36ddc899a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5660b7d3ef2044dca8d30c36ddc899a1"}}, "title": "Amplification-free long-read sequencing reveals unforeseen CRISPR-Cas9 off-target activity.", "authors": [{"family": "H\u00f6ijer", "given": "Ida", "initials": "I", "orcid": "0000-0002-3915-3384", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba4ce20b1b447ada4fdc8256211436e.json"}}, {"family": "Johansson", "given": "Josefin", "initials": "J"}, {"family": "Gudmundsson", "given": "Sanna", "initials": "S"}, {"family": "Chin", "given": "Chen-Shan", "initials": "CS"}, {"family": "Bunikis", "given": "Ignas", "initials": "I"}, {"family": "H\u00e4ggqvist", "given": "Susana", "initials": "S"}, {"family": "Emmanouilidou", "given": "Anastasia", "initials": "A"}, {"family": "Wilbe", "given": "Maria", "initials": "M"}, {"family": "den Hoed", "given": "Marcel", "initials": "M"}, {"family": "Bondeson", "given": "Marie-Louise", "initials": "ML"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}], "type": "journal article", "published": "2020-12-01", "journal": {"title": "Genome Biol.", "issn": "1474-760X", "volume": "21", "issue": "1", "pages": "290", "issn-l": "1474-7596"}, "abstract": "One ongoing concern about CRISPR-Cas9 genome editing is that unspecific guide RNA (gRNA) binding may induce off-target mutations. However, accurate prediction of CRISPR-Cas9 off-target activity is challenging. Here, we present SMRT-OTS and Nano-OTS, two novel, amplification-free, long-read sequencing protocols for detection of gRNA-driven digestion of genomic DNA by Cas9 in vitro.\n\nThe methods are assessed using the human cell line HEK293, re-sequenced at 18x coverage using highly accurate HiFi SMRT reads. SMRT-OTS and Nano-OTS are first applied to three different gRNAs targeting HEK293 genomic DNA, resulting in a set of 55 high-confidence gRNA cleavage sites identified by both methods. Twenty-five of these sites are not reported by off-target prediction software, either because they contain four or more single nucleotide mismatches or insertion/deletion mismatches, as compared with the human reference. Additional experiments reveal that 85% of Cas9 cleavage sites are also found by other in vitro-based methods and that on- and off-target sites are detectable in gene bodies where short-reads fail to uniquely align. Even though SMRT-OTS and Nano-OTS identify several sites with previously validated off-target editing activity in cells, our own CRISPR-Cas9 editing experiments in human fibroblasts do not give rise to detectable off-target mutations at the in vitro-predicted sites. However, indel and structural variation events are enriched at the on-target sites.\n\nAmplification-free long-read sequencing reveals Cas9 cleavage sites in vitro that would have been difficult to predict using computational tools, including in dark genomic regions inaccessible by short-read sequencing.", "doi": "10.1186/s13059-020-02206-w", "pmid": "33261648", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Technology development", "National Genomics Infrastructure": "Technology development", "Clinical Genomics Uppsala": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s13059-020-02206-w"}, {"db": "pmc", "key": "PMC7706270"}], "notes": [], "created": "2020-12-03T21:44:41.975Z", "modified": "2024-01-16T13:48:41.187Z"}, {"entity": "publication", "iuid": "cacdffc5e9214e87a523552b26690a9b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cacdffc5e9214e87a523552b26690a9b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cacdffc5e9214e87a523552b26690a9b"}}, "title": "Evaluation of Single-Molecule Sequencing Technologies for Structural Variant Detection in Two Swedish Human Genomes.", "authors": [{"family": "Fatima", "given": "Nazeefa", "initials": "N", "orcid": "0000-0001-7791-4984", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b6d2aa00c99444da15a97a9a0478568.json"}}, {"family": "Petri", "given": "Anna", "initials": "A"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}], "type": "journal article", "published": "2020-11-30", "journal": {"title": "Genes", "issn": "2073-4425", "volume": "11", "issue": "12", "pages": "1444", "issn-l": "2073-4425"}, "abstract": "Long-read single molecule sequencing is increasingly used in human genomics research, as it allows to accurately detect large-scale DNA rearrangements such as structural variations (SVs) at high resolution. However, few studies have evaluated the performance of different single molecule sequencing platforms for SV detection in human samples. Here we performed Oxford Nanopore Technologies (ONT) whole-genome sequencing of two Swedish human samples (average 32\u00d7 coverage) and compared the results to previously generated Pacific Biosciences (PacBio) data for the same individuals (average 66\u00d7 coverage). Our analysis inferred an average of 17k and 23k SVs from the ONT and PacBio data, respectively, with a majority of them overlapping with an available multi-platform SV dataset. When comparing the SV calls in the two Swedish individuals, we find a higher concordance between ONT and PacBio SVs detected in the same individual as compared to SVs detected by the same technology in different individuals. Downsampling of PacBio reads, performed to obtain similar coverage levels for all datasets, resulted in 17k SVs per individual and improved overlap with the ONT SVs. Our results suggest that ONT and PacBio have a similar performance for SV detection in human whole genome sequencing data, and that both technologies are feasible for population-scale studies.", "doi": "10.3390/genes11121444", "pmid": "33266238", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Technology development", "National Genomics Infrastructure": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "genes11121444"}, {"db": "pmc", "key": "PMC7760597"}], "notes": [], "created": "2020-12-03T21:45:04.193Z", "modified": "2024-01-16T13:48:41.275Z"}, {"entity": "publication", "iuid": "c54fad9a92ff45be90b06c461c2854cb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c54fad9a92ff45be90b06c461c2854cb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c54fad9a92ff45be90b06c461c2854cb"}}, "title": "Exploring autoantibody signatures in brain tissue from patients with severe mental illness.", "authors": [{"family": "Just", "given": "David", "initials": "D", "orcid": "0000-0001-6126-2256", "researcher": {"href": "https://publications.scilifelab.se/researcher/46f687d3a9cf4400932c75510807c764.json"}}, {"family": "M\u00e5nberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-0056-1313", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d155273b5b54e61b773f263e4f2ce9b.json"}}, {"family": "Mitsios", "given": "Nicholas", "initials": "N", "orcid": "0000-0001-6243-4953", "researcher": {"href": "https://publications.scilifelab.se/researcher/38efa44f5ed64192b432d6384584f00d.json"}}, {"family": "Stockmeier", "given": "Craig A", "initials": "CA", "orcid": "0000-0003-1861-1013", "researcher": {"href": "https://publications.scilifelab.se/researcher/89ebb5b73b9a42498192d35aea2d92c5.json"}}, {"family": "Rajkowska", "given": "Grazyna", "initials": "G", "orcid": "0000-0002-4348-4688", "researcher": {"href": "https://publications.scilifelab.se/researcher/4122635fead74359983624753ee365ff.json"}}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Mulder", "given": "Jan", "initials": "J", "orcid": "0000-0003-3717-5018", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8443b271929476bb2b569e39bae732c.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Cunningham", "given": "Janet L", "initials": "JL", "orcid": "0000-0001-7876-7779", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ab30dd6c6874bc7a227a8699c4a7085.json"}}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Carlstr\u00f6m", "given": "Eva Lindholm", "initials": "EL", "orcid": "0000-0001-8055-7826", "researcher": {"href": "https://publications.scilifelab.se/researcher/c433744d926b450097e71784b8bcc27c.json"}}], "type": "journal article", "published": "2020-11-18", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "10", "issue": "1", "pages": "401", "issn-l": "2158-3188"}, "abstract": "In recent years, studies have shown higher prevalence of autoantibodies in patients with schizophrenia compared to healthy individuals. This study applies an untargeted and a targeted affinity proteomics approach to explore and characterize the autoantibody repertoire in brain tissues from 73 subjects diagnosed with schizophrenia and 52 control subjects with no psychiatric or neurological disorders. Selected brain tissue lysates were first explored for IgG reactivity on planar microarrays composed of 11,520 protein fragments representing 10,820 unique proteins. Based on these results of ours and other previous studies of autoantibodies related to psychosis, we selected 226 fragments with an average length of 80 amino acids, representing 127 unique proteins. Tissue-based analysis of IgG reactivities using antigen suspension bead arrays was performed in a multiplex and parallel fashion for all 125 subjects. Among the detected autoantigens, higher IgG reactivity in subjects with schizophrenia, as compared to psychiatrically healthy subjects, was found against the glutamate ionotropic receptor NMDA type subunit 2D (anti-GluN2D). In a separate cohort with serum samples from 395 young adults with a wider spectrum of psychiatric disorders, higher levels of serum autoantibodies targeting GluN2D were found when compared to 102 control individuals. By further validating GluN2D and additional potential autoantigens, we will seek insights into how these are associated with severe mental illnesses.", "doi": "10.1038/s41398-020-01079-8", "pmid": "33208725", "labels": {"Autoimmunity and Serology Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-020-01079-8"}, {"db": "pmc", "key": "PMC7676257"}], "notes": [], "created": "2020-11-19T10:26:29.658Z", "modified": "2021-11-10T12:45:09.790Z"}, {"entity": "publication", "iuid": "11f33634ab3146e69138a533798e7438", "links": {"self": {"href": "https://publications.scilifelab.se/publication/11f33634ab3146e69138a533798e7438.json"}, "display": {"href": "https://publications.scilifelab.se/publication/11f33634ab3146e69138a533798e7438"}}, "title": "Identification and rescue of a tRNA wobble inosine deficiency causing intellectual disability disorder.", "authors": [{"family": "Ramos", "given": "Jillian", "initials": "J", "orcid": "0000-0001-8139-5793", "researcher": {"href": "https://publications.scilifelab.se/researcher/d56276e8c1ca41c7afe82887f174caf4.json"}}, {"family": "Proven", "given": "Melissa", "initials": "M"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Hagelskamp", "given": "Felix", "initials": "F"}, {"family": "Kuchinskaya", "given": "Ekaterina", "initials": "E"}, {"family": "Phelan", "given": "Benjamin", "initials": "B"}, {"family": "Bell", "given": "Ryan", "initials": "R"}, {"family": "Kellner", "given": "Stefanie M", "initials": "SM"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Fu", "given": "Dragony", "initials": "D", "orcid": "0000-0002-8725-8658", "researcher": {"href": "https://publications.scilifelab.se/researcher/77103dd473a54326a9af7151af9d2ef7.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "RNA", "issn": "1469-9001", "issn-l": "1355-8382", "volume": "26", "issue": "11", "pages": "1654-1666"}, "abstract": "The deamination of adenosine to inosine at the wobble position of tRNA is an essential post-transcriptional RNA modification required for wobble decoding in bacteria and eukaryotes. In humans, the wobble inosine modification is catalyzed by the heterodimeric ADAT2/3 complex. Here, we describe novel pathogenic ADAT3 variants impairing adenosine deaminase activity through a distinct mechanism that can be corrected through expression of the heterodimeric ADAT2 subunit. The variants were identified in a family in which all three siblings exhibit intellectual disability linked to biallelic variants in the ADAT3 locus. The biallelic ADAT3 variants result in a missense variant converting alanine to valine at a conserved residue or the introduction of a premature stop codon in the deaminase domain. Fibroblast cells derived from two ID-affected individuals exhibit a reduction in tRNA wobble inosine levels and severely diminished adenosine tRNA deaminase activity. Notably, the ADAT3 variants exhibit impaired interaction with the ADAT2 subunit and alterations in ADAT2-dependent nuclear localization. Based upon these findings, we find that tRNA adenosine deaminase activity and wobble inosine modification can be rescued in patient cells by overexpression of the ADAT2 catalytic subunit. These results uncover a key role for the inactive ADAT3 deaminase domain in proper assembly with ADAT2 and demonstrate that ADAT2/3 nuclear import is required for maintaining proper levels of the wobble inosine modification in tRNA.", "doi": "10.1261/rna.076380.120", "pmid": "32763916", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "Clinical Genomics Uppsala": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "rna.076380.120"}, {"db": "pmc", "key": "PMC7566568"}], "notes": [], "created": "2020-09-15T07:06:13.955Z", "modified": "2024-01-16T13:48:41.471Z"}, {"entity": "publication", "iuid": "3f9436baa42849ed95e219bbf949416e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3f9436baa42849ed95e219bbf949416e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3f9436baa42849ed95e219bbf949416e"}}, "title": "Whole genome sequencing of familial isolated oesophagus atresia uncover shared structural variants.", "authors": [{"family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "researcher": {"href": "https://publications.scilifelab.se/researcher/3310cb2ab70f43d78cc7cd7e36ac8f83.json"}}, {"family": "Engstrand-Lilja", "given": "Helene", "initials": "H"}, {"family": "Maqbool", "given": "Khurram", "initials": "K"}, {"family": "Mattisson", "given": "Jonas", "initials": "J"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2020-06-26", "journal": {"title": "BMC Med Genomics", "issn": "1755-8794", "volume": "13", "issue": "1", "pages": "85", "issn-l": "1755-8794"}, "abstract": "Oesophageal atresia (OA) is a life-threatening developmental defect characterized by a lost continuity between the upper and lower oesophagus. The most common form is a distal connection between the trachea and the oesophagus, i.e. a tracheoesophageal fistula (TEF). The condition may be part of a syndrome or occurs as an isolated feature. The recurrence risk in affected families is increased compared to the population-based incidence suggesting contributing genetic factors.\n\nTo gain insight into gene variants and genes associated with isolated OA we conducted whole genome sequencing on samples from three families with recurrent cases affected by congenital and isolated TEF.\n\nWe identified a combination of single nucleotide variants (SNVs), splice site variants (SSV) and structural variants (SV) annotated to altogether 100 coding genes in the six affected individuals.\n\nThis study highlights rare SVs among candidate gene variants in our individuals with OA and provides a gene framework for further investigations of genetic factors behind this malformation.", "doi": "10.1186/s12920-020-00737-6", "pmid": "32586322", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12920-020-00737-6"}, {"db": "pmc", "key": "PMC7318369"}], "notes": [], "created": "2020-07-03T05:25:29.915Z", "modified": "2024-01-16T13:48:42.333Z"}, {"entity": "publication", "iuid": "8e7d434d65094896b5c0c4f4328ae62e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8e7d434d65094896b5c0c4f4328ae62e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8e7d434d65094896b5c0c4f4328ae62e"}}, "title": "Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes.", "authors": [{"family": "Etemadikhah", "given": "Mitra", "initials": "M", "orcid": "0000-0001-5795-9085", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e68ca63254a4b5697188bb87087852f.json"}}, {"family": "Niazi", "given": "Adnan", "initials": "A", "orcid": "0000-0003-0311-5279", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9e07c9891804a60980eb07956a7cd0d.json"}}, {"family": "Wetterberg", "given": "Lennart", "initials": "L"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2020-01-20", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "630", "issn-l": "2045-2322"}, "abstract": "Schizophrenia is a complex neurodevelopmental disorder with high rate of morbidity and mortality. While the heritability rate is high, the precise etiology is still unknown. Although schizophrenia is a central nervous system disorder, studies using peripheral tissues have also been established to search for patient specific biomarkers and to increase understanding of schizophrenia etiology. Among all peripheral tissues, fibroblasts stand out as they are easy to obtain and culture. Furthermore, they keep genetic stability for long period and exhibit molecular similarities to cells from nervous system. Using a unique set of fibroblast samples from a genetically isolated population in northern Sweden, we performed whole transcriptome sequencing to compare differentially expressed genes in seven controls and nine patients. We found differential fibroblast expression between cases and controls for 48 genes, including eight genes previously implicated in schizophrenia or schizophrenia related pathways; HGF, PRRT2, EGR1, EGR3, C11orf87, TLR3, PLEKHH2 and PIK3CD. Weighted gene correlation network analysis identified three differentially co-expressed networks of genes significantly-associated with schizophrenia. All three modules were significantly suppressed in patients compared to control, with one module highly enriched in genes involved in synaptic plasticity, behavior and synaptic transmission. In conclusion, our results support the use of fibroblasts for identification of differentially expressed genes in schizophrenia and highlight dysregulation of synaptic networks as an important mechanism in schizophrenia.", "doi": "10.1038/s41598-020-57467-z", "pmid": "31959813", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-57467-z"}, {"db": "pmc", "key": "PMC6971273"}], "notes": [], "created": "2020-07-03T05:23:47.172Z", "modified": "2024-01-16T13:48:43.065Z"}, {"entity": "publication", "iuid": "c0c6515cc557485e8d3397ecadcfd64b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c0c6515cc557485e8d3397ecadcfd64b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c0c6515cc557485e8d3397ecadcfd64b"}}, "title": "Linkage and exome analysis implicate multiple genes in non-syndromic intellectual disability in a large Swedish family.", "authors": [{"family": "Lindholm Carlstr\u00f6m", "given": "Eva", "initials": "E", "orcid": "0000-0001-8055-7826", "researcher": {"href": "https://publications.scilifelab.se/researcher/c433744d926b450097e71784b8bcc27c.json"}}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Etemadikhah", "given": "Mitra", "initials": "M"}, {"family": "Wetterberg", "given": "Lennart", "initials": "L"}, {"family": "Gustavson", "given": "Karl-Henrik", "initials": "KH"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2019-11-06", "journal": {"volume": "12", "issn": "1755-8794", "issue": "1", "pages": "156", "title": "BMC Med Genomics", "issn-l": "1755-8794"}, "abstract": "Non-syndromic intellectual disability is genetically heterogeneous with dominant, recessive and complex forms of inheritance. We have performed detailed genetic studies in a large multi-generational Swedish family, including several members diagnosed with non-syndromic intellectual disability. Linkage analysis was performed on 22 family members, nine affected with mild to moderate intellectual disability and 13 unaffected family members.\n\nFamily members were analyzed with Affymetrix Genome-Wide Human SNP Array 6.0 and the genetic data was used to detect copy number variation and to perform genome wide linkage analysis with the SNP High Throughput Linkage analysis system and the Merlin software. For the exome sequencing, the samples were prepared using the Sure Select Human All Exon Kit (Agilent Technologies, Santa Clara, CA, USA) and sequenced using the Ion Proton\u2122 System. Validation of identified variants was performed with Sanger sequencing.\n\nThe linkage analysis results indicate that intellectual disability in this family is genetically heterogeneous, with suggestive linkage found on chromosomes 1q31-q41, 4q32-q35, 6p25 and 14q24-q31 (LOD scores of 2.4, simulated p-value of 0.000003 and a simulated genome-wide p-value of 0.06). Exome sequencing was then performed in 14 family members and 7 unrelated individuals from the same region. The analysis of coding variation revealed a pathogenic and candidate variants in different branches of the family. In three patients we find a known homozygous pathogenic mutation in the Homo sapiens solute carrier family 17 member 5 (SLC17A5), causing Salla disease. We also identify a deletion overlapping KDM3B and a duplication overlapping MAP3K4 and AGPAT4, both overlapping variants previously reported in developmental disorders.\n\nDNA samples from the large family analyzed in this study were initially collected based on a hypothesis that affected members shared a major genetic risk factor. Our results show that a complex phenotype such as mild intellectual disability in large families from genetically isolated populations may show considerable genetic heterogeneity.", "doi": "10.1186/s12920-019-0606-4", "pmid": "31694657", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12920-019-0606-4"}, {"db": "pmc", "key": "PMC6833288"}], "notes": [], "created": "2019-11-25T14:38:27.833Z", "modified": "2024-01-16T13:48:43.569Z"}, {"entity": "publication", "iuid": "0c401a8a00204400a4b68ae689b2d8d2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0c401a8a00204400a4b68ae689b2d8d2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0c401a8a00204400a4b68ae689b2d8d2"}}, "title": "Novel Y-Chromosome Long Non-Coding RNAs Expressed in Human Male CNS During Early Development.", "authors": [{"family": "Johansson", "given": "Martin M", "initials": "MM"}, {"family": "Pottmeier", "given": "Philipp", "initials": "P"}, {"family": "Suciu", "given": "Pascalina", "initials": "P"}, {"family": "Ahmad", "given": "Tauseef", "initials": "T"}, {"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Darj", "given": "Elisabeth", "initials": "E"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Peuckert", "given": "Christiane", "initials": "C"}, {"family": "Jazin", "given": "Elena", "initials": "E"}], "type": "journal article", "published": "2019-09-24", "journal": {"volume": "10", "issn": "1664-8021", "issue": null, "pages": "891", "title": "Front Genet", "issn-l": "1664-8021"}, "abstract": "Global microarray gene expression analyses previously demonstrated differences in female and male embryos during neurodevelopment. In particular, before sexual maturation of the gonads, the differences seem to concentrate on the expression of genes encoded on the X- and Y-chromosomes. To investigate genome-wide differences in expression during this early developmental window, we combined high-resolution RNA sequencing with qPCR to analyze brain samples from human embryos during the first trimester of development. Our analysis was tailored for maximum sensitivity to discover Y-chromosome gene expression, but at the same time, it was underpowered to detect X-inactivation escapees. Using this approach, we found that 5 out of 13 expressed gametolog pairs showed unbalanced gene dosage, and as a consequence, a male-biased expression. In addition, we found six novel non-annotated long non-coding RNAs on the Y-chromosome with conserved expression patterns in newborn chimpanzee. The tissue specific and time-restricted expression of these long non-coding RNAs strongly suggests important functions during central nervous system development in human males.", "doi": "10.3389/fgene.2019.00891", "pmid": "31608120", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6769107"}], "notes": [], "created": "2019-11-25T15:05:37.096Z", "modified": "2024-01-16T13:48:43.835Z"}, {"entity": "publication", "iuid": "a83f57593e954660884b10ae5e2254a4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a83f57593e954660884b10ae5e2254a4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a83f57593e954660884b10ae5e2254a4"}}, "title": "Whole genome sequencing of consanguineous families reveals novel pathogenic variants in intellectual disability.", "authors": [{"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC", "orcid": "0000-0002-4018-5551", "researcher": {"href": "https://publications.scilifelab.se/researcher/829bcbc2bb734d848f7b370546aca35c.json"}}, {"family": "Soussi Zander", "given": "Cecilia", "initials": "C"}, {"family": "Zhao", "given": "Jin J", "initials": "JJ"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Maqbool", "given": "Khurram", "initials": "K", "orcid": "0000-0003-2981-2582", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ea06b85057744018f754c373fef3ca5.json"}}, {"family": "M\u00e5nsson", "given": "Else", "initials": "E"}, {"family": "Stenninger", "given": "Eric", "initials": "E"}, {"family": "Holmlund", "given": "Ulrika", "initials": "U"}, {"family": "\u00d6hrner", "given": "Ylva", "initials": "Y"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "letter", "published": "2019-03-00", "journal": {"volume": "95", "issn": "1399-0004", "issue": "3", "pages": "436-439", "title": "Clin. Genet.", "issn-l": "0009-9163"}, "abstract": null, "doi": "10.1111/cge.13470", "pmid": "30525197", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Clinical Genomics Uppsala": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC6392105"}], "notes": [], "created": "2019-01-07T18:03:32.030Z", "modified": "2021-06-21T13:53:42.462Z"}, {"entity": "publication", "iuid": "ee94eab47af144b0a91add67c1458f35", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee94eab47af144b0a91add67c1458f35.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee94eab47af144b0a91add67c1458f35"}}, "title": "Expression profiling and in situ screening of circular RNAs in human tissues.", "authors": [{"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Wu", "given": "Chenglin", "initials": "C"}, {"family": "Westholm", "given": "Jakub Orzechowski", "initials": "JO", "orcid": "0000-0002-6849-6220", "researcher": {"href": "https://publications.scilifelab.se/researcher/161d8b5fb6734b33ad5f5590edbc0cff.json"}}, {"family": "Niazi", "given": "Adnan", "initials": "A", "orcid": "0000-0003-0311-5279", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9e07c9891804a60980eb07956a7cd0d.json"}}, {"family": "Manivannan", "given": "Manimozhi", "initials": "M"}, {"family": "Bramlett", "given": "Kelli", "initials": "K"}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2018-11-16", "journal": {"volume": "8", "issn": "2045-2322", "issue": "1", "pages": "16953", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Circular RNAs (circRNAs) were recently discovered as a class of widely expressed noncoding RNA and have been implicated in regulation of gene expression. However, the function of the majority of circRNAs remains unknown. Studies of circRNAs have been hampered by a lack of essential approaches for detection, quantification and visualization. We therefore developed a target-enrichment sequencing method suitable for screening of circRNAs and their linear counterparts in large number of samples. We also applied padlock probes and in situ sequencing to visualize and determine circRNA localization in human brain tissue at subcellular levels. We measured circRNA abundance across different human samples and tissues. Our results highlight the potential of this RNA class to act as a specific diagnostic marker in blood and serum, by detection of circRNAs from genes exclusively expressed in the brain. The powerful and scalable tools we present will enable studies of circRNA function and facilitate screening of circRNA as diagnostic biomarkers.", "doi": "10.1038/s41598-018-35001-6", "pmid": "30446675", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Technology development", "National Genomics Infrastructure": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative", "In Situ Sequencing": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-018-35001-6"}, {"db": "pmc", "key": "PMC6240052"}], "notes": [], "created": "2018-11-19T13:50:06.813Z", "modified": "2025-10-17T13:02:18.588Z"}, {"entity": "publication", "iuid": "3f6c987638d84add91fc127d7dc6af75", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3f6c987638d84add91fc127d7dc6af75.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3f6c987638d84add91fc127d7dc6af75"}}, "title": "De Novo Assembly of Two Swedish Genomes Reveals Missing Segments from the Human GRCh38 Reference and Improves Variant Calling of Population-Scale Sequencing Data.", "authors": [{"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Che", "given": "Huiwen", "initials": "H"}, {"family": "Martin", "given": "Marcel", "initials": "M", "orcid": "0000-0002-0680-200X", "researcher": {"href": "https://publications.scilifelab.se/researcher/132afd4fea2e4e86bdf43708c8f49907.json"}}, {"family": "Bunikis", "given": "Ignas", "initials": "I"}, {"family": "Dahlberg", "given": "Johan", "initials": "J"}, {"family": "H\u00f6ijer", "given": "Ida", "initials": "I", "orcid": "0000-0002-3915-3384", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba4ce20b1b447ada4fdc8256211436e.json"}}, {"family": "H\u00e4ggqvist", "given": "Susana", "initials": "S"}, {"family": "Vezzi", "given": "Francesco", "initials": "F"}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Olason", "given": "Pall", "initials": "P"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2018-10-09", "journal": {"volume": "9", "issn": "2073-4425", "issue": "10", "pages": "486", "title": "Genes", "issn-l": "2073-4425"}, "abstract": "The current human reference sequence (GRCh38) is a foundation for large-scale sequencing projects. However, recent studies have suggested that GRCh38 may be incomplete and give a suboptimal representation of specific population groups. Here, we performed a de novo assembly of two Swedish genomes that revealed over 10 Mb of sequences absent from the human GRCh38 reference in each individual. Around 6 Mb of these novel sequences (NS) are shared with a Chinese personal genome. The NS are highly repetitive, have an elevated GC-content, and are primarily located in centromeric or telomeric regions. Up to 1 Mb of NS can be assigned to chromosome Y, and large segments are also missing from GRCh38 at chromosomes 14, 17, and 21. Inclusion of NS into the GRCh38 reference radically improves the alignment and variant calling from short-read whole-genome sequencing data at several genomic loci. A re-analysis of a Swedish population-scale sequencing project yields > 75,000 putative novel single nucleotide variants (SNVs) and removes > 10,000 false positive SNV calls per individual, some of which are located in protein coding regions. Our results highlight that the GRCh38 reference is not yet complete and demonstrate that personal genome assemblies from local populations can improve the analysis of short-read whole-genome sequencing data.", "doi": "10.3390/genes9100486", "pmid": "30304863", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "genes9100486"}, {"db": "pmc", "key": "PMC6210158"}], "notes": [], "created": "2018-11-20T14:44:03.808Z", "modified": "2024-01-16T13:48:45.362Z"}, {"entity": "publication", "iuid": "b4d4451c7e4b49bca2ca64e753e5cf5c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b4d4451c7e4b49bca2ca64e753e5cf5c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b4d4451c7e4b49bca2ca64e753e5cf5c"}}, "title": "Detailed analysis of HTT repeat elements in human blood using targeted amplification-free long-read sequencing.", "authors": [{"family": "H\u00f6ijer", "given": "Ida", "initials": "I", "orcid": "0000-0002-3915-3384", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba4ce20b1b447ada4fdc8256211436e.json"}}, {"family": "Tsai", "given": "Yu-Chih", "initials": "YC"}, {"family": "Clark", "given": "Tyson A", "initials": "TA"}, {"family": "Kotturi", "given": "Paul", "initials": "P"}, {"family": "Dahl", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8122-0800", "researcher": {"href": "https://publications.scilifelab.se/researcher/689e06ddc001490a8cb891050ba5a732.json"}}, {"family": "Stattin", "given": "Eva-Lena", "initials": "EL"}, {"family": "Bondeson", "given": "Marie-Louise", "initials": "ML"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}], "type": "journal article", "published": "2018-09-00", "journal": {"volume": "39", "issn": "1098-1004", "issue": "9", "pages": "1262-1272", "title": "Hum. Mutat.", "issn-l": "1059-7794"}, "abstract": "Amplification of DNA is required as a mandatory step during library preparation in most targeted sequencing protocols. This can be a critical limitation when targeting regions that are highly repetitive or with extreme guanine-cytosine (GC) content, including repeat expansions associated with human disease. Here, we used an amplification-free protocol for targeted enrichment utilizing the CRISPR/Cas9 system (No-Amp Targeted sequencing) in combination with single molecule, real-time (SMRT) sequencing for studying repeat elements in the huntingtin (HTT) gene, where an expanded CAG repeat is causative for Huntington disease. We also developed a robust data analysis pipeline for repeat element analysis that is independent of alignment of reads to a reference genome. The method was applied to 11 diagnostic blood samples, and for all 22 alleles the resulting CAG repeat count agreed with previous results based on fragment analysis. The amplification-free protocol also allowed for studying somatic variability of repeat elements in our samples, without the interference of PCR stutter. In summary, with No-Amp Targeted sequencing in combination with our analysis pipeline, we could accurately study repeat elements that are difficult to investigate using PCR-based methods.", "doi": "10.1002/humu.23580", "pmid": "29932473", "labels": {"National Genomics Infrastructure": "Technology development", "NGI Uppsala (Uppsala Genome Center)": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6175010"}], "notes": [], "created": "2018-10-15T09:36:08.234Z", "modified": "2024-01-16T13:48:45.682Z"}, {"entity": "publication", "iuid": "4aec1dba6cd84d518d4a8fcd4450b703", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4aec1dba6cd84d518d4a8fcd4450b703.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4aec1dba6cd84d518d4a8fcd4450b703"}}, "title": "Exome sequencing reveals NAA15 and PUF60 as candidate genes associated with intellectual disability.", "authors": [{"family": "Zhao", "given": "Jin J", "initials": "JJ", "orcid": "0000-0001-8367-8391", "researcher": {"href": "https://publications.scilifelab.se/researcher/fad3b22c21064a85a351f549bedfc36e.json"}}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Zander", "given": "Cecilia S", "initials": "CS"}, {"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Georgii-Hemming", "given": "Patrik", "initials": "P"}, {"family": "M\u00e5nsson", "given": "Else", "initials": "E"}, {"family": "Brandberg", "given": "G\u00f6ran", "initials": "G"}, {"family": "S\u00e4vmarker", "given": "Helena E", "initials": "HE"}, {"family": "Frykholm", "given": "Carina", "initials": "C"}, {"family": "Kuchinskaya", "given": "Ekaterina", "initials": "E"}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2018-01-00", "journal": {"volume": "177", "issn": "1552-485X", "issue": "1", "title": "Am. J. Med. Genet. B Neuropsychiatr. Genet.", "pages": "10-20", "issn-l": "1552-4841"}, "abstract": "Intellectual Disability (ID) is a clinically heterogeneous condition that affects 2-3% of population worldwide. In recent years, exome sequencing has been a successful strategy for studies of genetic causes of ID, providing a growing list of both candidate and validated ID genes. In this study, exome sequencing was performed on 28 ID patients in 27 patient-parent trios with the aim to identify de novo variants (DNVs) in known and novel ID associated genes. We report the identification of 25 DNVs out of which five were classified as pathogenic or likely pathogenic. Among these, a two base pair deletion was identified in the PUF60 gene, which is one of three genes in the critical region of the 8q24.3 microdeletion syndrome (Verheij syndrome). Our result adds to the growing evidence that PUF60 is responsible for the majority of the symptoms reported for carriers of a microdeletion across this region. We also report variants in several genes previously not associated with ID, including a de novo missense variant in NAA15. We highlight NAA15 as a novel candidate ID gene based on the vital role of NAA15 in the generation and differentiation of neurons in neonatal brain, the fact that the gene is highly intolerant to loss of function and coding variation, and previously reported DNVs in neurodevelopmental disorders.", "doi": "10.1002/ajmg.b.32574", "pmid": "28990276", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5765476"}], "notes": [], "created": "2017-11-02T16:04:48.503Z", "modified": "2024-01-16T13:48:47.230Z"}, {"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": "14eb5706d8aa4e83800ec409e0517584", "links": {"self": {"href": "https://publications.scilifelab.se/publication/14eb5706d8aa4e83800ec409e0517584.json"}, "display": {"href": "https://publications.scilifelab.se/publication/14eb5706d8aa4e83800ec409e0517584"}}, "title": "Reduced cell surface levels of GPI-linked markers in a new case with PIGG loss of function.", "authors": [{"family": "Zhao", "given": "Jin James", "initials": "JJ", "orcid": "0000-0001-8367-8391", "researcher": {"href": "https://publications.scilifelab.se/researcher/fad3b22c21064a85a351f549bedfc36e.json"}}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Knaus", "given": "Alexej", "initials": "A"}, {"family": "Georgii-Hemming", "given": "Patrik", "initials": "P"}, {"family": "Baeck", "given": "Peter", "initials": "P"}, {"family": "Krawitz", "given": "Peter M", "initials": "PM"}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2017-10-00", "journal": {"volume": "38", "issn": "1098-1004", "issue": "10", "pages": "1394-1401", "title": "Hum. Mutat.", "issn-l": "1059-7794"}, "abstract": "Glycosylphosphatidylinositol (GPI) is a glycolipid that tethers more than 150 different proteins to the cell surface. Aberrations in biosynthesis of GPI anchors cause congenital disorders of glycosylation with clinical features including intellectual disability (ID), seizures, and facial dysmorphism. Here, we present two siblings with ID, cerebellar hypoplasia, cerebellar ataxia, early-onset seizures, and minor facial dysmorphology. Using exome sequencing, we identified a homozygous nonsense variant (NM_001127178.1:c.1640G>A, p.Trp547*) in the gene Phosphatidylinositol Glycan Anchor Biosynthesis, Class G (PIGG) in both the patients. Variants in several other GPI anchor synthesis genes lead to a reduced expression of GPI-anchored proteins (GPI-APs) that can be measured by flow cytometry. No significant differences in GPI-APs could be detected in patient granulocytes, consistent with recent findings. However, fibroblasts showed a reduced global level of GPI anchors and of specific GPI-linked markers. These findings suggest that fibroblasts might be more sensitive to pathogenic variants in GPI synthesis pathway and are well suited to screen for GPI-anchor deficiencies. Based on genetic and functional evidence, we confirm that pathogenic variants in PIGG cause an ID syndrome, and we find that loss of function of PIGG is associated with GPI deficiency.", "doi": "10.1002/humu.23268", "pmid": "28581210", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6180480"}], "notes": [], "created": "2017-10-17T09:44:01.955Z", "modified": "2024-01-16T13:48:47.470Z"}, {"entity": "publication", "iuid": "ad795dcc608c4f42b717d331ebed654d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ad795dcc608c4f42b717d331ebed654d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ad795dcc608c4f42b717d331ebed654d"}}, "title": "Mutations in HECW2 are associated with intellectual disability and epilepsy.", "authors": [{"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Zhao", "given": "Jin J", "initials": "JJ"}, {"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Wentzel", "given": "Christian", "initials": "C"}, {"family": "Georgii-Hemming", "given": "Patrik", "initials": "P"}, {"family": "M\u00e5nsson", "given": "Else", "initials": "E"}, {"family": "Ederth S\u00e4vmarker", "given": "Helena", "initials": "H"}, {"family": "Brandberg", "given": "G\u00f6ran", "initials": "G"}, {"family": "Soussi Zander", "given": "Cecilia", "initials": "C"}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2016-10-00", "journal": {"volume": "53", "issn": "1468-6244", "issue": "10", "pages": "697-704", "title": "J. Med. Genet.", "issn-l": "0022-2593"}, "abstract": "De novo mutations are a frequent cause of disorders related to brain development. We report the results of screening patients diagnosed with both epilepsy and intellectual disability (ID) using exome sequencing to identify known and new causative de novo mutations relevant to these conditions.\n\nExome sequencing was performed on 39 patient-parent trios to identify de novo mutations. Clinical significance of de novo mutations in genes was determined using the American College of Medical Genetics and Genomics standard guidelines for interpretation of coding variants. Variants in genes of unknown clinical significance were further analysed in the context of previous trio sequencing efforts in neurodevelopmental disorders.\n\nIn 39 patient-parent trios we identified 29 de novo mutations in coding sequence. Analysis of de novo and inherited variants yielded a molecular diagnosis in 11 families (28.2%). In combination with previously published exome sequencing results in neurodevelopmental disorders, our analysis implicates HECW2 as a novel candidate gene in ID and epilepsy.\n\nOur results support the use of exome sequencing as a diagnostic approach for ID and epilepsy, and confirm previous results regarding the importance of de novo mutations in this patient group. The results also highlight the utility of network analysis and comparison to previous large-scale studies as strategies to prioritise candidate genes for further studies. This study adds knowledge to the increasingly growing list of causative and candidate genes in ID and epilepsy and highlights HECW2 as a new candidate gene for neurodevelopmental disorders.", "doi": "10.1136/jmedgenet-2016-103814", "pmid": "27334371", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "jmedgenet-2016-103814"}, {"db": "pmc", "key": "PMC5099177"}], "notes": [], "created": "2017-05-03T13:00:18.318Z", "modified": "2024-01-16T13:48:49.374Z"}, {"entity": "publication", "iuid": "848d4b0d2a994164ab961b4f93de1c03", "links": {"self": {"href": "https://publications.scilifelab.se/publication/848d4b0d2a994164ab961b4f93de1c03.json"}, "display": {"href": "https://publications.scilifelab.se/publication/848d4b0d2a994164ab961b4f93de1c03"}}, "title": "A Role for the Chromatin-Remodeling Factor BAZ1A in Neurodevelopment.", "authors": [{"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Zhao", "given": "Jin J", "initials": "JJ"}, {"family": "Etemadikhah", "given": "Mitra", "initials": "M"}, {"family": "Kalushkova", "given": "Antonia", "initials": "A"}, {"family": "Konska", "given": "Katarzyna", "initials": "K"}, {"family": "Jernberg-Wiklund", "given": "Helena", "initials": "H"}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2016-09-00", "journal": {"volume": "37", "issn": "1098-1004", "issue": "9", "pages": "964-975", "title": "Hum. Mutat.", "issn-l": "1059-7794"}, "abstract": "Chromatin-remodeling factors are required for a wide range of cellular and biological processes including development and cognition, mainly by regulating gene expression. As these functions would predict, deregulation of chromatin-remodeling factors causes various disease syndromes, including neurodevelopmental disorders. Recent reports have linked mutations in several genes coding for chromatin-remodeling factors to intellectual disability (ID). Here, we used exome sequencing and identified a nonsynonymous de novo mutation in BAZ1A (NM_182648.2:c.4043T > G, p.Phe1348Cys), encoding the ATP-utilizing chromatin assembly and remodeling factor 1 (ACF1), in a patient with unexplained ID. ACF1 has been previously reported to bind to the promoter of the vitamin D receptor (VDR)-regulated genes and suppress their expression. Our results show that the patient displays decreased binding of ACF1 to the promoter of the VDR-regulated gene CYP24A1. Using RNA sequencing, we find that the mutation affects the expression of genes involved in several pathways including vitamin D metabolism, Wnt signaling and synaptic formation. RNA sequencing of BAZ1A knockdown cells and Baz1a knockout mice revealed that BAZ1A carry out distinctive functions in different tissues. We also demonstrate that BAZ1A depletion influence the expression of genes important for nervous system development and function. Our data point to an important role for BAZ1A in neurodevelopment, and highlight a possible link for BAZ1A to ID.", "doi": "10.1002/humu.23034", "pmid": "27328812", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6681169"}], "notes": [], "created": "2017-05-03T12:59:44.944Z", "modified": "2024-01-16T13:48:49.578Z"}, {"entity": "publication", "iuid": "3c586a1c4f7544feade7f95aedd83c3d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c586a1c4f7544feade7f95aedd83c3d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c586a1c4f7544feade7f95aedd83c3d"}}, "title": "One CNV Discordance in NRXN1 Observed Upon Genome-wide Screening in 38 Pairs of Adult Healthy Monozygotic Twins.", "authors": [{"family": "Magnusson", "given": "Patrik K E", "initials": "PK"}, {"family": "Lee", "given": "Donghwan", "initials": "D"}, {"family": "Chen", "given": "Xu", "initials": "X"}, {"family": "Szatkiewicz", "given": "Jin", "initials": "J"}, {"family": "Pramana", "given": "Setia", "initials": "S"}, {"family": "Teo", "given": "Shumei", "initials": "S"}, {"family": "Sullivan", "given": "Patrick F", "initials": "PF"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Pawitan", "given": "Yudi", "initials": "Y"}], "type": "journal article", "published": "2016-04-00", "journal": {"volume": "19", "issn": "1832-4274", "issue": "2", "pages": "97-103", "title": "Twin Res Hum Genet", "issn-l": null}, "abstract": "Monozygotic (MZ) twins stem from the same single fertilized egg and therefore share all their inherited genetic variation. This is one of the unequivocal facts on which genetic epidemiology and twin studies are based. To what extent this also implies that MZ twins share genotypes in adult tissues is not precisely established, but a common pragmatic assumption is that MZ twins are 100% genetically identical also in adult tissues. During the past decade, this view has been challenged by several reports, with observations of differences in post-zygotic copy number variations (CNVs) between members of the same MZ pair. In this study, we performed a systematic search for differences of CNVs within 38 adult MZ pairs who had been misclassified as dizygotic (DZ) twins by questionnaire-based assessment. Initial scoring by PennCNV suggested a total of 967 CNV discordances. The within-pair correlation in number of CNVs detected was strongly dependent on confidence score filtering and reached a plateau of r = 0.8 when restricting to CNVs detected with confidence score larger than 50. The top-ranked discordances were subsequently selected for validation by quantitative polymerase chain reaction (qPCR), from which one single ~120kb deletion in NRXN1 on chromosome 2 (bp 51017111-51136802) was validated. Despite involving an exon, no sign of cognitive/mental consequences was apparent in the affected twin pair, potentially reflecting limited or lack of expression of the transcripts containing this exon in nerve/brain.", "doi": "10.1017/thg.2016.5", "pmid": "26899349", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S1832427416000050"}], "notes": [], "created": "2017-05-08T07:57:23.429Z", "modified": "2024-01-16T13:48:50.288Z"}, {"entity": "publication", "iuid": "cceb2f966a7a4621b24afa4a5f902959", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cceb2f966a7a4621b24afa4a5f902959.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cceb2f966a7a4621b24afa4a5f902959"}}, "title": "Spatial sexual dimorphism of X and Y homolog gene expression in the human central nervous system during early male development.", "authors": [{"family": "Johansson", "given": "Martin M", "initials": "MM"}, {"family": "Lundin", "given": "Elin", "initials": "E"}, {"family": "Qian", "given": "Xiaoyan", "initials": "X"}, {"family": "Mirzazadeh", "given": "Mohammadreza", "initials": "M"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Darj", "given": "Elisabeth", "initials": "E"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}, {"family": "Jazin", "given": "Elena", "initials": "E"}], "type": "journal article", "published": "2016-01-12", "journal": {"volume": "7", "issn": "2042-6410", "issue": null, "pages": "5", "title": "Biol Sex Differ", "issn-l": "2042-6410"}, "abstract": "Renewed attention has been directed to the functions of the Y chromosome in the central nervous system during early human male development, due to the recent proposed involvement in neurodevelopmental diseases. PCDH11Y and NLGN4Y are of special interest because they belong to gene families involved in cell fate determination and formation of dendrites and axon.\n\nWe used RNA sequencing, immunocytochemistry and a padlock probing and rolling circle amplification strategy, to distinguish the expression of X and Y homologs in situ in the human brain for the first time. To minimize influence of androgens on the sex differences in the brain, we focused our investigation to human embryos at 8-11 weeks post-gestation.\n\nWe found that the X- and Y-encoded genes are expressed in specific and heterogeneous cellular sub-populations of both glial and neuronal origins. More importantly, we found differential distribution patterns of X and Y homologs in the male developing central nervous system.\n\nThis study has visualized the spatial distribution of PCDH11X/Y and NLGN4X/Y in human developing nervous tissue. The observed spatial distribution patterns suggest the existence of an additional layer of complexity in the development of the male CNS.", "doi": "10.1186/s13293-015-0056-4", "pmid": "26759715", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "56"}, {"db": "pmc", "key": "PMC4710049"}], "notes": [], "created": "2017-05-03T13:00:23.114Z", "modified": "2024-01-16T13:48:50.609Z"}, {"entity": "publication", "iuid": "0251a2b4aed046f19b1bcc4ff2c51ccc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0251a2b4aed046f19b1bcc4ff2c51ccc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0251a2b4aed046f19b1bcc4ff2c51ccc"}}, "title": "Transcriptome Profiling Reveals Degree of Variability in Induced Pluripotent Stem Cell Lines: Impact for Human Disease Modeling.", "authors": [{"family": "Schuster", "given": "Jens", "initials": "J"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Pilar Lorenzo", "given": "Laureanne", "initials": "L"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Sobol", "given": "Maria", "initials": "M"}, {"family": "Raykova", "given": "Doroteya", "initials": "D"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2015-10-00", "journal": {"volume": "17", "issn": "2152-4998", "issue": "5", "pages": "327-337", "title": "Cell Reprogram", "issn-l": "2152-4971"}, "abstract": "Induced pluripotent stem cell (iPSC) technology has become an important tool for disease modeling. Insufficient data on the variability among iPSC lines derived from a single somatic parental cell line have in practice led to generation and analysis of several, usually three, iPSC sister lines from each parental cell line. We established iPSC lines from a human fibroblast line (HDF-K1) and used transcriptome sequencing to investigate the variation among three sister lines (iPSC-K1A, B, and C). For comparison, we analyzed the transcriptome of an iPSC line (iPSC-K5B) derived from a different fibroblast line (HDF-K5), a human embryonic stem cell (ESC) line (ESC-HS181), as well as the two parental fibroblast lines. All iPSC lines fulfilled stringent criteria for pluripotency. In an unbiased cluster analysis, all stem cell lines (four iPSCs and one ESC) clustered together as opposed to the parental fibroblasts. The transcriptome profiles of the three iPSC sister lines were indistinguishable from each other, and functional pathway analysis did not reveal any significant hits. In contrast, the expression profiles of the ESC line and the iPSC-K5B line were distinct from that of the sister lines iPSC-K1A, B, and C. Differentiation to embryoid bodies and subsequent analysis of germ layer markers in the five stem cell clones confirmed that the distribution of their expression profiles was retained. Taken together, our observations stress the importance of using iPSCs of different parental origin rather than several sister iPSC lines to distinguish disease-associated mechanisms from genetic background effects in disease modeling.", "doi": "10.1089/cell.2015.0009", "pmid": "26348590", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [], "notes": [], "created": "2017-05-02T12:57:24.674Z", "modified": "2021-07-07T14:37:06.368Z"}, {"entity": "publication", "iuid": "ee38afb802cf41a3b90de64ccbb53f24", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee38afb802cf41a3b90de64ccbb53f24.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee38afb802cf41a3b90de64ccbb53f24"}}, "title": "Abolished InsP3R2 function inhibits sweat secretion in both humans and mice.", "authors": [{"family": "Klar", "given": "Joakim", "initials": "J"}, {"family": "Hisatsune", "given": "Chihiro", "initials": "C"}, {"family": "Baig", "given": "Shahid M", "initials": "SM"}, {"family": "Tariq", "given": "Muhammad", "initials": "M"}, {"family": "Johansson", "given": "Anna C V", "initials": "AC"}, {"family": "Rasool", "given": "Mahmood", "initials": "M"}, {"family": "Malik", "given": "Naveed Altaf", "initials": "NA"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Sugiura", "given": "Kotomi", "initials": "K"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Mikoshiba", "given": "Katsuhiko", "initials": "K"}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2014-11-00", "journal": {"volume": "124", "issn": "1558-8238", "issue": "11", "pages": "4773-4780", "title": "J. Clin. Invest.", "issn-l": "0021-9738"}, "abstract": "There are 3 major sweat-producing glands present in skin; eccrine, apocrine, and apoeccrine glands. Due to the high rate of secretion, eccrine sweating is a vital regulator of body temperature in response to thermal stress in humans; therefore, an inability to sweat (anhidrosis) results in heat intolerance that may cause impaired consciousness and death. Here, we have reported 5 members of a consanguineous family with generalized, isolated anhidrosis, but morphologically normal eccrine sweat glands. Whole-genome analysis identified the presence of a homozygous missense mutation in ITPR2, which encodes the type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2), that was present in all affected family members. We determined that the mutation is localized within the pore forming region of InsP3R2 and abrogates Ca2+ release from the endoplasmic reticulum, which suggests that intracellular Ca2+ release by InsP3R2 in clear cells of the sweat glands is important for eccrine sweat production. Itpr2-/- mice exhibited a marked reduction in sweat secretion, and evaluation of sweat glands from Itpr2-/- animals revealed a decrease in Ca2+ response compared with controls. Together, our data indicate that loss of InsP3R2-mediated Ca2+ release causes isolated anhidrosis in humans and suggest that specific InsP3R inhibitors have the potential to reduce sweat production in hyperhidrosis.", "doi": "10.1172/JCI70720", "pmid": "25329695", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "70720"}, {"db": "pmc", "key": "PMC4347256"}], "notes": [], "created": "2017-05-04T15:02:42.254Z", "modified": "2021-07-07T14:37:06.641Z"}, {"entity": "publication", "iuid": "a00ad8c035184402b413a525bef51199", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a00ad8c035184402b413a525bef51199.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a00ad8c035184402b413a525bef51199"}}, "title": "Splicing in the human brain.", "authors": [{"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2014-08-31", "journal": {"volume": "116", "issn": "2162-5514", "issue": null, "pages": "95-125", "title": "Int. Rev. Neurobiol.", "issn-l": "0074-7742"}, "abstract": "It has become increasingly clear over the past decade that RNA has important functions in human cells beyond its role as an intermediate translator of DNA to protein. It is now known that RNA plays highly specific roles in pathways involved in regulatory, structural, and catalytic functions. The complexity of RNA production and regulation has become evident with the advent of high-throughput methods to study the transcriptome. Deep sequencing has revealed an enormous diversity of RNA types and transcript isoforms in human cells. The transcriptome of the human brain is particularly interesting as it contains more expressed genes than other tissues and also displays an extreme diversity of transcript isoforms, indicating that highly complex regulatory pathways are present in the brain. Several of these regulatory proteins are now identified, including RNA-binding proteins that are neuron specific. RNA-binding proteins also play important roles in regulating the splicing process and the temporal and spatial isoform production. While significant progress has been made in understanding the human transcriptome, many questions still remain regarding the basic mechanisms of splicing and subcellular localization of RNA. A long-standing question is to what extent the splicing of pre-mRNA is cotranscriptional and posttranscriptional, respectively. Recent data, including studies of the human brain, indicate that splicing is primarily cotranscriptional in human cells. This chapter describes the current understanding of splicing and splicing regulation in the human brain and discusses the recent global sequence-based analyses of transcription and splicing.", "doi": "10.1016/B978-0-12-801105-8.00005-9", "pmid": "25172473", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "B978-0-12-801105-8.00005-9"}], "notes": [], "created": "2017-05-04T14:58:39.749Z", "modified": "2021-07-08T12:52:24.396Z"}, {"entity": "publication", "iuid": "ff05473b33024d5c9f21023b2d66771d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ff05473b33024d5c9f21023b2d66771d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ff05473b33024d5c9f21023b2d66771d"}}, "title": "Efficient cellular fractionation improves RNA sequencing analysis of mature and nascent transcripts from human tissues.", "authors": [{"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Nyberg", "given": "Linnea", "initials": "L"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Grabherr", "given": "Manfred", "initials": "M"}, {"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2013-11-13", "journal": {"volume": "13", "issn": "1472-6750", "issue": null, "pages": "99", "title": "BMC Biotechnol.", "issn-l": "1472-6750"}, "abstract": "The starting material for RNA sequencing (RNA-seq) studies is usually total RNA or polyA+ RNA. Both forms of RNA represent heterogeneous pools of RNA molecules at different levels of maturation and processing. Such heterogeneity, in addition to the biases associated with polyA+ purification steps, may influence the analysis, sensitivity and the interpretation of RNA-seq data. We hypothesize that subcellular fractions of RNA may provide a more accurate picture of gene expression.\n\nWe present results for sequencing of cytoplasmic and nuclear RNA after cellular fractionation of tissue samples. In comparison with conventional polyA+ RNA, the cytoplasmic RNA contains a significantly higher fraction of exonic sequence, providing increased sensitivity in expression analysis and splice junction detection, and in improved de novo assembly of RNA-seq data. Conversely, the nuclear fraction shows an enrichment of unprocessed RNA compared with total RNA-seq, making it suitable for analysis of nascent transcripts and RNA processing dynamics.\n\nOur results show that cellular fractionation is a more rapid and cost effective approach than conventional polyA+ enrichment when studying mature RNAs. Thus, RNA-seq of separated cytosolic and nuclear RNA can significantly improve the analysis of complex transcriptomes from mammalian tissues.", "doi": "10.1186/1472-6750-13-99", "pmid": "24225116", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "1472-6750-13-99"}, {"db": "pmc", "key": "PMC3833653"}], "notes": [], "created": "2017-05-04T14:57:49.079Z", "modified": "2021-07-08T12:52:24.453Z"}, {"entity": "publication", "iuid": "2b008514b5c44b6eae6b951bc4351d20", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2b008514b5c44b6eae6b951bc4351d20.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2b008514b5c44b6eae6b951bc4351d20"}}, "title": "Genome-wide association study of susceptibility loci for cervical cancer.", "authors": [{"family": "Chen", "given": "Dan", "initials": "D"}, {"family": "Juko-Pecirep", "given": "Ivana", "initials": "I"}, {"family": "Hammer", "given": "Joanna", "initials": "J"}, {"family": "Ivansson", "given": "Emma", "initials": "E"}, {"family": "Enroth", "given": "Stefan", "initials": "S"}, {"family": "Gustavsson", "given": "Inger", "initials": "I"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PK"}, {"family": "McKay", "given": "James D", "initials": "JD"}, {"family": "Wilander", "given": "Erik", "initials": "E"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2013-05-01", "journal": {"volume": "105", "issn": "1460-2105", "issue": "9", "pages": "624-633", "title": "J. Natl. Cancer Inst.", "issn-l": "0027-8874"}, "abstract": "Cervical carcinoma has a heritable genetic component, but the genetic basis of cervical cancer is still not well understood.\n\nWe performed a genome-wide association study of 731 422 single nucleotide polymorphisms (SNPs) in 1075 cervical cancer case subjects and 4014 control subjects and replicated it in 1140 case subjects and 1058 control subjects. The association between top SNPs and cervical cancer was estimated by odds ratios (ORs) and 95% confidence intervals (CIs) with unconditional logistic regression. All statistical tests were two-sided.\n\nThree independent loci in the major histocompatibility complex (MHC) region at 6p21.3 were associated with cervical cancer: the first is adjacent to the MHC class I polypeptide-related sequence A gene (MICA) (rs2516448; OR = 1.42, 95% CI = 1.31 to 1.54; P = 1.6\u00d710(-18)); the second is between HLA-DRB1 and HLA-DQA1 (rs9272143; OR = 0.67, 95% CI = 0.62 to 0.72; P = 9.3\u00d710(-24)); and the third is at HLA-DPB2 (rs3117027; OR=1.25, 95% CI = 1.15 to 1.35; P = 4.9\u00d710(-8)). We also confirmed previously reported associations of B*0702 and DRB1*1501-DQB1*0602 with susceptibility to and DRB1*1301-DQA1*0103-DQB1*0603 with protection against cervical cancer. The three new loci are statistically independent of these specific human leukocyte antigen alleles/haplotypes. MICA encodes a membrane-bound protein that acts as a ligand for NKG2D to activate antitumor effects. The risk allele of rs2516448 is in perfect linkage disequilibrium with a frameshift mutation (A5.1) of MICA, which results in a truncated protein. Functional analysis shows that women carrying this mutation have lower levels of membrane-bound MICA.\n\nThree novel loci in the MHC may affect susceptibility to cervical cancer in situ, including the MICA-A5.1 allele that may cause impaired immune activation and increased risk of tumor development.", "doi": "10.1093/jnci/djt051", "pmid": "23482656", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "djt051"}], "notes": [], "created": "2017-05-04T14:58:02.378Z", "modified": "2021-07-07T14:15:07.518Z"}, {"entity": "publication", "iuid": "1a04315aeec743cfa0478d39b62901a6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1a04315aeec743cfa0478d39b62901a6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1a04315aeec743cfa0478d39b62901a6"}}, "title": "RNA-binding protein QKI regulates Glial fibrillary acidic protein expression in human astrocytes.", "authors": [{"family": "Radomska", "given": "Katarzyna J", "initials": "KJ"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Reinius", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Lindholm Carlstr\u00f6m", "given": "Eva", "initials": "E"}, {"family": "Emilsson", "given": "Lina", "initials": "L"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Jazin", "given": "Elena", "initials": "E"}], "type": "journal article", "published": "2013-04-01", "journal": {"volume": "22", "issn": "1460-2083", "issue": "7", "pages": "1373-1382", "title": "Hum. Mol. Genet.", "issn-l": "0964-6906"}, "abstract": "Linkage, association and expression studies previously pointed to the human QKI, KH domain containing, RNA-binding (QKI) as a candidate gene for schizophrenia. Functional studies of the mouse orthologue Qk focused mainly on its role in oligodendrocyte development and myelination, while its function in astroglia remained unexplored. Here, we show that QKI is highly expressed in human primary astrocytes and that its splice forms encode proteins targeting different subcellular localizations. Uncovering the role of QKI in astrocytes is of interest in light of growing evidence implicating astrocyte dysfunction in the pathogenesis of several disorders of the central nervous system. We selectively silenced QKI splice variants in human primary astrocytes and used RNA sequencing to identify differential expression and splice variant composition at the genome-wide level. We found that an mRNA expression of Glial fibrillary acidic protein (GFAP), encoding a major component of astrocyte intermediate filaments, was down-regulated after QKI7 splice variant silencing. Moreover, we identified a potential QKI-binding site within the 3' untranslated region of human GFAP. This sequence was not conserved between mice and humans, raising the possibility that GFAP is a target for QKI in humans but not rodents. Haloperidol treatment of primary astrocytes resulted in coordinated increases in QKI7 and GFAP expression. Taken together, our results provide the first link between QKI and GFAP, two genes with alterations previously observed independently in schizophrenic patients. Our findings for QKI, together with its well-known role in myelination, suggest that QKI is a hub regulator of glia function in humans.", "doi": "10.1093/hmg/dds553", "pmid": "23321059", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "dds553"}], "notes": [], "created": "2017-05-04T15:02:25.213Z", "modified": "2021-07-07T14:15:07.503Z"}, {"entity": "publication", "iuid": "f1019b2b1539445d99fb17566d00cb69", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f1019b2b1539445d99fb17566d00cb69.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f1019b2b1539445d99fb17566d00cb69"}}, "title": "Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing.", "authors": [{"family": "Klar", "given": "Joakim", "initials": "J"}, {"family": "Sobol", "given": "Maria", "initials": "M"}, {"family": "Melberg", "given": "Atle", "initials": "A"}, {"family": "M\u00e4bert", "given": "Katrin", "initials": "K"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Johansson", "given": "Anna C V", "initials": "AC"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Entesarian", "given": "Miriam", "initials": "M"}, {"family": "Orl\u00e9n", "given": "Hanna", "initials": "H"}, {"family": "Casar-Borota", "given": "Olivera", "initials": "O"}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2013-04-00", "journal": {"volume": "34", "issn": "1098-1004", "issue": "4", "pages": "572-577", "title": "Hum. Mutat.", "issn-l": "1059-7794"}, "abstract": "Welander distal myopathy (WDM) is an adult onset autosomal dominant disorder characterized by distal limb weakness, which progresses slowly from the fifth decade. All WDM patients are of Swedish or Finnish descent and share a rare chromosome 2p13 haplotype. We restricted the WDM-associated haplotype followed by whole exome sequencing. Within the conserved haplotype, we identified a single heterozygous mutation c.1150G>A (p.E384K) in T-cell intracellular antigen-1 (TIA1) in all WDM patients investigated (n = 43). The TIA1 protein regulates splicing, and translation through direct interaction with mRNA and the p.E384K mutation is located in the C-terminal Q-rich domain that interacts with the U1-C splicing factor. TIA1 has been shown to prevent skipping of SMN2 exon 7, and we show that WDM patients have increased levels of spliced SMN2 in skeletal muscle cells when compared with controls. Immunostaining of WDM muscle biopsies showed accumulation of TIA1 and stress granulae proteins adjacent to intracellular inclusions, a typical finding in WDM. The combined findings strongly suggest that the TIA1 mutation causes perturbed RNA splicing and cellular stress resulting in WDM. The selection against the mutation is likely to be negligible and the age of the TIA1 founder mutation was calculated to approximately 1,050 years, which coincides with the epoch of early seafaring across the Baltic Sea.", "doi": "10.1002/humu.22282", "pmid": "23348830", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:57:57.873Z", "modified": "2021-07-07T14:37:06.652Z"}, {"entity": "publication", "iuid": "32222c65cf914e8ba642562dc9c16b20", "links": {"self": {"href": "https://publications.scilifelab.se/publication/32222c65cf914e8ba642562dc9c16b20.json"}, "display": {"href": "https://publications.scilifelab.se/publication/32222c65cf914e8ba642562dc9c16b20"}}, "title": "Exome RNA sequencing reveals rare and novel alternative transcripts.", "authors": [{"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2013-01-07", "journal": {"volume": "41", "issn": "1362-4962", "issue": "1", "pages": "e6", "title": "Nucleic Acids Res.", "issn-l": "0305-1048"}, "abstract": "RNA sequencing has become an important method to perform hypothesis-free characterization of global gene expression. One of the limitations of RNA sequencing is that most sequence reads represent highly expressed transcripts, whereas low level transcripts are challenging to detect. To combine the benefits of traditional expression arrays with the advantages of RNA sequencing, we have used whole exome enrichment prior to sequencing of total RNA. We show that whole exome capture can be successfully applied to cDNA to study the transcriptional landscape in human tissues. By introducing the exome enrichment step, we are able to identify transcripts present at very low levels, which are below the level of detection in conventional RNA sequencing. Although the enrichment increases the ability to detect presence of transcripts, it also lowers the accuracy of quantification of expression levels. Our results yield a large number of novel exons and splice isoforms, suggesting that conventional RNA sequencing methods only detect a small fraction of the full transcript diversity. We propose that whole exome enrichment of RNA is a suitable strategy for genome-wide discovery of novel transcripts, alternative splice variants and fusion genes.", "doi": "10.1093/nar/gks816", "pmid": "22941640", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "gks816"}, {"db": "pmc", "key": "PMC3592422"}], "notes": [], "created": "2017-05-04T14:58:08.941Z", "modified": "2021-07-07T14:15:07.525Z"}, {"entity": "publication", "iuid": "d94da77410ff4e17a03dcc005cecffe2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d94da77410ff4e17a03dcc005cecffe2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d94da77410ff4e17a03dcc005cecffe2"}}, "title": "Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder.", "authors": [{"family": "Hooper", "given": "Sean D", "initials": "SD"}, {"family": "Johansson", "given": "Anna C V", "initials": "AC"}, {"family": "Tellgren-Roth", "given": "Christian", "initials": "C"}, {"family": "Stattin", "given": "Eva-Lena", "initials": "EL"}, {"family": "Dahl", "given": "Niklas", "initials": "N"}, {"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2012-12-19", "journal": {"volume": "13", "issn": "1471-2350", "issue": null, "pages": "123", "title": "BMC Med. Genet.", "issn-l": "1471-2350"}, "abstract": "Tourette Syndrome (TS) is a neuropsychiatric disorder in children characterized by motor and verbal tics. Although several genes have been suggested in the etiology of TS, the genetic mechanisms remain poorly understood.\n\nUsing cytogenetics and FISH analysis, we identified an apparently balanced t(6,22)(q16.2;p13) in a male patient with TS and obsessive-compulsive disorder (OCD). In order to map the breakpoints and to identify additional submicroscopic rearrangements, we performed whole genome mate-pair sequencing and CGH-array analysis on DNA from the proband.\n\nSequence and CGH array analysis revealed a 400 kb deletion located 1.3 Mb telomeric of the chromosome 6q breakpoint, which has not been reported in controls. The deletion affects three genes (GPR63, NDUFA4 and KLHL32) and overlaps a region previously found deleted in a girl with autistic features and speech delay. The proband's mother, also a carrier of the translocation, was diagnosed with OCD and shares the deletion. We also describe a further potentially related rearrangement which, while unmapped in Homo sapiens, was consistent with the chimpanzee genome.\n\nWe conclude that genome-wide sequencing at relatively low resolution can be used for the identification of submicroscopic rearrangements. We also show that large rearrangements may escape detection using standard analysis of whole genome sequencing data. Our findings further provide a candidate region for TS and OCD on chromosome 6q16.", "doi": "10.1186/1471-2350-13-123", "pmid": "23253088", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "1471-2350-13-123"}, {"db": "pmc", "key": "PMC3556158"}], "notes": [], "created": "2017-05-04T14:57:31.238Z", "modified": "2021-07-08T12:52:24.439Z"}, {"entity": "publication", "iuid": "23f07fa1366140489ae6b485aefa3f41", "links": {"self": {"href": "https://publications.scilifelab.se/publication/23f07fa1366140489ae6b485aefa3f41.json"}, "display": {"href": "https://publications.scilifelab.se/publication/23f07fa1366140489ae6b485aefa3f41"}}, "title": "Intractable epilepsy of infancy due to homozygous mutation in the EFHC1 gene.", "authors": [{"family": "Berger", "given": "Itai", "initials": "I"}, {"family": "Dor", "given": "Talya", "initials": "T"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Edvardson", "given": "Simon", "initials": "S"}, {"family": "Shaag", "given": "Avraham", "initials": "A"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Elpeleg", "given": "Orly", "initials": "O"}], "type": "case reports", "published": "2012-08-00", "journal": {"volume": "53", "issn": "1528-1167", "issue": "8", "pages": "1436-1440", "title": "Epilepsia", "issn-l": "0013-9580"}, "abstract": "The molecular etiology of primary intractable epilepsy in infancy is largely unknown. We studied a nonconsanguineous Moroccan-Jewish family, where three of their seven children presented with intractable seizures and died at 18-36 months.\n\nHomozygous regions were searched using 250 K DNA single nucleotide polymorphism (SNP) array. The sequence of 50 Mb exome of a single patient was determined using SOLiD 5500XL deep sequencing analyzer.\n\nA single homozygous 11.3 Mb genomic region on chromosome 6 was linked to the disease in this family. This region contained 110 genes encoding a total of 1,000 exons. Whole exome sequencing revealed a single pathogenic homozygous variant within the critical region. The mutation, Phe229Leu in the EFHC1 gene was previously shown, in a carrier state, to be associated with juvenile myoclonic epilepsy.\n\nAlthough heterozygosity for the Phe229Leu mutation is known to be associated with a relatively benign form of epilepsy in adolescence; homozygosity for the same mutation is associated with lethal epilepsy of infancy. Given the considerable carrier rate of this mutation worldwide, the sequence of the EFHC1 gene should be determined in all patients with primary intractable epilepsy in infancy.", "doi": "10.1111/j.1528-1167.2012.03536.x", "pmid": "22690745", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:57:33.057Z", "modified": "2021-07-07T14:15:07.510Z"}, {"entity": "publication", "iuid": "77b8c1e7b0a14bd4940ea15e8f8ed19a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/77b8c1e7b0a14bd4940ea15e8f8ed19a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/77b8c1e7b0a14bd4940ea15e8f8ed19a"}}, "title": "Genetic adaptation of fatty-acid metabolism: a human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids.", "authors": [{"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Enroth", "given": "Stefan", "initials": "S"}, {"family": "Johansson", "given": "Asa", "initials": "A"}, {"family": "Zaboli", "given": "Ghazal", "initials": "G"}, {"family": "Igl", "given": "Wilmar", "initials": "W"}, {"family": "Johansson", "given": "Anna C V", "initials": "AC"}, {"family": "Rivas", "given": "Manuel A", "initials": "MA"}, {"family": "Daly", "given": "Mark J", "initials": "MJ"}, {"family": "Schmitz", "given": "Gerd", "initials": "G"}, {"family": "Hicks", "given": "Andrew A", "initials": "AA"}, {"family": "Meitinger", "given": "Thomas", "initials": "T"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "van Duijn", "given": "Cornelia", "initials": "C"}, {"family": "Oostra", "given": "Ben", "initials": "B"}, {"family": "Pramstaller", "given": "Peter P", "initials": "PP"}, {"family": "Rudan", "given": "Igor", "initials": "I"}, {"family": "Wright", "given": "Alan F", "initials": "AF"}, {"family": "Wilson", "given": "James F", "initials": "JF"}, {"family": "Campbell", "given": "Harry", "initials": "H"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2012-05-04", "journal": {"volume": "90", "issn": "1537-6605", "issue": "5", "pages": "809-820", "title": "Am. J. Hum. Genet.", "issn-l": "0002-9297"}, "abstract": "Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFAs) are essential for the development and function of the human brain. They can be obtained directly from food, e.g., fish, or synthesized from precursor molecules found in vegetable oils. To determine the importance of genetic variability to fatty-acid biosynthesis, we studied FADS1 and FADS2, which encode rate-limiting enzymes for fatty-acid conversion. We performed genome-wide genotyping (n = 5,652 individuals) and targeted resequencing (n = 960 individuals) of the FADS region in five European population cohorts. We also analyzed available genomic data from human populations, archaic hominins, and more distant primates. Our results show that present-day humans have two common FADS haplotypes-defined by 28 closely linked SNPs across 38.9 kb-that differ dramatically in their ability to generate LC-PUFAs. No independent effects on FADS activity were seen for rare SNPs detected by targeted resequencing. The more efficient, evolutionarily derived haplotype appeared after the lineage split leading to modern humans and Neanderthals and shows evidence of positive selection. This human-specific haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and thereby might have provided an advantage in environments with limited access to dietary LC-PUFAs. In the modern world, this haplotype has been associated with lifestyle-related diseases, such as coronary artery disease.", "doi": "10.1016/j.ajhg.2012.03.014", "pmid": "22503634", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "S0002-9297(12)00158-9"}, {"db": "pmc", "key": "PMC3376635"}], "notes": [], "created": "2017-05-04T14:57:28.310Z", "modified": "2021-07-07T14:37:06.520Z"}, {"entity": "publication", "iuid": "586f6b11de1d47dba7ce229c441380b4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/586f6b11de1d47dba7ce229c441380b4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/586f6b11de1d47dba7ce229c441380b4"}}, "title": "Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2.", "authors": [{"family": "Spiegel", "given": "Ronen", "initials": "R"}, {"family": "Pines", "given": "Ophry", "initials": "O"}, {"family": "Ta-Shma", "given": "Asaf", "initials": "A"}, {"family": "Burak", "given": "Efrat", "initials": "E"}, {"family": "Shaag", "given": "Avraham", "initials": "A"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Edvardson", "given": "Shimon", "initials": "S"}, {"family": "Mahajna", "given": "Muhammad", "initials": "M"}, {"family": "Zenvirt", "given": "Shamir", "initials": "S"}, {"family": "Saada", "given": "Ann", "initials": "A"}, {"family": "Shalev", "given": "Stavit", "initials": "S"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Elpeleg", "given": "Orly", "initials": "O"}], "type": "journal article", "published": "2012-03-09", "journal": {"volume": "90", "issn": "1537-6605", "issue": "3", "pages": "518-523", "title": "Am. J. Hum. Genet.", "issn-l": "0002-9297"}, "abstract": "Degeneration of the cerebrum, cerebellum, and retina in infancy is part of the clinical spectrum of lysosomal storage disorders, mitochondrial respiratory chain defects, carbohydrate glycosylation defects, and infantile neuroaxonal dystrophy. We studied eight individuals from two unrelated families who presented at 2-6 months of age with truncal hypotonia and athetosis, seizure disorder, and ophthalmologic abnormalities. Their course was characterized by failure to acquire developmental milestones and culminated in profound psychomotor retardation and progressive visual loss, including optic nerve and retinal atrophy. Despite their debilitating state, the disease was compatible with survival of up to 18 years. Laboratory investigations were normal, but the oxidation of glutamate by muscle mitochondria was slightly reduced. Serial brain MRI displayed progressive, prominent cerebellar atrophy accompanied by thinning of the corpus callosum, dysmyelination, and frontal and temporal cortical atrophy. Homozygosity mapping followed by whole-exome sequencing disclosed a Ser112Arg mutation in ACO2, encoding mitochondrial aconitase, a component of the Krebs cycle. Specific aconitase activity in the individuals' lymphoblasts was severely reduced. Under restrictive conditions, the mutant human ACO2 failed to complement a yeast ACO1 deletion strain, whereas the wild-type human ACO2 succeeded, indicating that this mutation is pathogenic. Thus, a defect in mitochondrial aconitase is associated with an infantile neurodegenerative disorder affecting mainly the cerebellum and retina. In the absence of noninvasive biomarkers, determination of the ACO2 sequence or of aconitase activity in lymphoblasts are warranted in similarly affected individuals, based on clinical and neuroradiologic grounds.", "doi": "10.1016/j.ajhg.2012.01.009", "pmid": "22405087", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "S0002-9297(12)00043-2"}, {"db": "pmc", "key": "PMC3309186"}], "notes": [], "created": "2017-05-04T14:57:28.614Z", "modified": "2021-07-07T14:15:07.577Z"}, {"entity": "publication", "iuid": "bb6519b0dd8d478ebba28f1e622005ec", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb6519b0dd8d478ebba28f1e622005ec.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb6519b0dd8d478ebba28f1e622005ec"}}, "title": "Total RNA sequencing reveals nascent transcription and widespread co-transcriptional splicing in the human brain.", "authors": [{"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Zaghlool", "given": "Ammar", "initials": "A"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Wetterbom", "given": "Anna", "initials": "A"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2011-11-06", "journal": {"volume": "18", "issn": "1545-9985", "issue": "12", "pages": "1435-1440", "title": "Nat. Struct. Mol. Biol.", "issn-l": "1545-9985"}, "abstract": "Transcriptome sequencing allows for analysis of mature RNAs at base pair resolution. Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription. We sequenced total RNA from human brain and liver and found a large fraction of reads (up to 40%) within introns. Intronic RNAs were abundant in brain tissue, particularly for genes involved in axonal growth and synaptic transmission. Moreover, we detected significant differences in intronic RNA levels between fetal and adult brains. We show that the pattern of intronic sequence read coverage is explained by nascent transcription in combination with co-transcriptional splicing. Further analysis of co-transcriptional splicing indicates a correlation between slowly removed introns and alternative splicing. Our data show that sequencing of total RNA provides unique insight into the transcriptional processes in the cell, with particular importance for normal brain development.", "doi": "10.1038/nsmb.2143", "pmid": "22056773", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "nsmb.2143"}], "notes": [], "created": "2017-05-04T14:57:22.242Z", "modified": "2021-07-08T12:52:24.403Z"}, {"entity": "publication", "iuid": "c3cf03b072144a19b7eca8c6cb472c37", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c3cf03b072144a19b7eca8c6cb472c37.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c3cf03b072144a19b7eca8c6cb472c37"}}, "title": "Identification of novel exons and transcribed regions by chimpanzee transcriptome sequencing.", "authors": [{"family": "Wetterbom", "given": "Anna", "initials": "A"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}], "type": "journal article", "published": "2010-07-23", "journal": {"volume": "11", "issn": "1474-760X", "issue": "7", "pages": "R78", "title": "Genome Biol.", "issn-l": "1474-7596"}, "abstract": "We profile the chimpanzee transcriptome by using deep sequencing of cDNA from brain and liver, aiming to quantify expression of known genes and to identify novel transcribed regions.\n\nUsing stringent criteria for transcription, we identify 12,843 expressed genes, with a majority being found in both tissues. We further identify 9,826 novel transcribed regions that are not overlapping with annotated exons, mRNAs or ESTs. Over 80% of the novel transcribed regions map within or in the vicinity of known genes, and by combining sequencing data with de novo splice predictions we predict several of the novel transcribed regions to be new exons or 3' UTRs. For approximately 350 novel transcribed regions, the corresponding DNA sequence is absent in the human reference genome. The presence of novel transcribed regions in five genes and in one intergenic region is further validated with RT-PCR. Finally, we describe and experimentally validate a putative novel multi-exon gene that belongs to the ATP-cassette transporter gene family. This gene does not appear to be functional in human since one exon is absent from the human genome. In addition to novel exons and UTRs, novel transcribed regions may also stem from different types of noncoding transcripts. We note that expressed repeats and introns from unspliced mRNAs are especially common in our data.\n\nOur results extend the chimpanzee gene catalogue with a large number of novel exons and 3' UTRs and thus support the view that mammalian gene annotations are not yet complete.", "doi": "10.1186/gb-2010-11-7-r78", "pmid": "20653958", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "gb-2010-11-7-r78"}, {"db": "pmc", "key": "PMC2926789"}], "notes": [], "created": "2017-05-04T14:57:11.055Z", "modified": "2021-07-08T12:52:24.418Z"}, {"entity": "publication", "iuid": "7607d00abcf8496ab4d3c0821314931f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7607d00abcf8496ab4d3c0821314931f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7607d00abcf8496ab4d3c0821314931f"}}, "title": "Global and unbiased detection of splice junctions from RNA-seq data.", "authors": [{"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Wetterbom", "given": "Anna", "initials": "A"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2010-03-17", "journal": {"volume": "11", "issn": "1474-760X", "issue": "3", "pages": "R34", "title": "Genome Biol.", "issn-l": "1474-7596"}, "abstract": "We have developed a new strategy for de novo prediction of splice junctions in short-read RNA-seq data, suitable for detection of novel splicing events and chimeric transcripts. When tested on mouse RNA-seq data, >31,000 splice events were predicted, of which 88% bridged between two regions separated by <or=100 kb, and 74% connected two exons of the same RefSeq gene. Our method also reports genomic rearrangements such as insertions and deletions.", "doi": "10.1186/gb-2010-11-3-r34", "pmid": "20236510", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "gb-2010-11-3-r34"}, {"db": "pmc", "key": "PMC2864574"}], "notes": [], "created": "2017-05-04T14:57:10.753Z", "modified": "2021-07-07T14:37:06.514Z"}]}