Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
  • 2
    Publication Date: 2011-08-13
    Description: Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC) II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537168/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537168/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Star, Bastiaan -- Nederbragt, Alexander J -- Jentoft, Sissel -- Grimholt, Unni -- Malmstrom, Martin -- Gregers, Tone F -- Rounge, Trine B -- Paulsen, Jonas -- Solbakken, Monica H -- Sharma, Animesh -- Wetten, Ola F -- Lanzen, Anders -- Winer, Roger -- Knight, James -- Vogel, Jan-Hinnerk -- Aken, Bronwen -- Andersen, Oivind -- Lagesen, Karin -- Tooming-Klunderud, Ave -- Edvardsen, Rolf B -- Tina, Kirubakaran G -- Espelund, Mari -- Nepal, Chirag -- Previti, Christopher -- Karlsen, Bard Ove -- Moum, Truls -- Skage, Morten -- Berg, Paul R -- Gjoen, Tor -- Kuhl, Heiner -- Thorsen, Jim -- Malde, Ketil -- Reinhardt, Richard -- Du, Lei -- Johansen, Steinar D -- Searle, Steve -- Lien, Sigbjorn -- Nilsen, Frank -- Jonassen, Inge -- Omholt, Stig W -- Stenseth, Nils Chr -- Jakobsen, Kjetill S -- 098051/Wellcome Trust/United Kingdom -- England -- Nature. 2011 Aug 10;477(7363):207-10. doi: 10.1038/nature10342.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Ecological and Evolutionary Synthesis, Department of Biology, University of Oslo, PO Box 1066, Blindern, N-0316 Oslo, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21832995" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Evolution, Molecular ; Gadus morhua/*genetics/*immunology ; Genome/*genetics ; Genomics ; Hemoglobins/genetics ; Immune System/*immunology ; Immunity/*genetics/immunology ; Major Histocompatibility Complex/genetics/immunology ; Male ; Polymorphism, Genetic/genetics ; Synteny/genetics ; Toll-Like Receptors/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2014-02-18
    Description: A core promoter is a stretch of DNA surrounding the transcription start site (TSS) that integrates regulatory inputs and recruits general transcription factors to initiate transcription. The nature and causative relationship of the DNA sequence and chromatin signals that govern the selection of most TSSs by RNA polymerase II remain unresolved. Maternal to zygotic transition represents the most marked change of the transcriptome repertoire in the vertebrate life cycle. Early embryonic development in zebrafish is characterized by a series of transcriptionally silent cell cycles regulated by inherited maternal gene products: zygotic genome activation commences at the tenth cell cycle, marking the mid-blastula transition. This transition provides a unique opportunity to study the rules of TSS selection and the hierarchy of events linking transcription initiation with key chromatin modifications. We analysed TSS usage during zebrafish early embryonic development at high resolution using cap analysis of gene expression, and determined the positions of H3K4me3-marked promoter-associated nucleosomes. Here we show that the transition from the maternal to zygotic transcriptome is characterized by a switch between two fundamentally different modes of defining transcription initiation, which drive the dynamic change of TSS usage and promoter shape. A maternal-specific TSS selection, which requires an A/T-rich (W-box) motif, is replaced with a zygotic TSS selection grammar characterized by broader patterns of dinucleotide enrichments, precisely aligned with the first downstream (+1) nucleosome. The developmental dynamics of the H3K4me3-marked nucleosomes reveal their DNA-sequence-associated positioning at promoters before zygotic transcription and subsequent transcription-independent adjustment to the final position downstream of the zygotic TSS. The two TSS-defining grammars coexist, often physically overlapping, in core promoters of constitutively expressed genes to enable their expression in the two regulatory environments. The dissection of overlapping core promoter determinants represents a framework for future studies of promoter structure and function across different regulatory contexts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haberle, Vanja -- Li, Nan -- Hadzhiev, Yavor -- Plessy, Charles -- Previti, Christopher -- Nepal, Chirag -- Gehrig, Jochen -- Dong, Xianjun -- Akalin, Altuna -- Suzuki, Ana Maria -- van IJcken, Wilfred F J -- Armant, Olivier -- Ferg, Marco -- Strahle, Uwe -- Carninci, Piero -- Muller, Ferenc -- Lenhard, Boris -- MC_UP_1102/1/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2014 Mar 20;507(7492):381-5. doi: 10.1038/nature12974. Epub 2014 Feb 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biology, University of Bergen, Thormohlensgate 53A, N-5008 Bergen, Norway [2] Institute of Clinical Sciences and MRC Clinical Sciences Center, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK [3]. ; 1] School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK [2]. ; School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. ; 1] RIKEN Omics Science Center, Yokohama, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, RIKEN Yokohama Campus, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; 1] Computational Biology Unit, Uni Computing, Uni Research AS, University of Bergen, Thormohlensgate 55, N-5008 Bergen, Norway [2] German Cancer Research Center (DKFZ), Genomics & Proteomics Core Facility (GPCF), Im Neuenheimer Feld 580/TP3, Heidelberg 69120, Germany (C.Pr.); Broegelmann Research Laboratory, The Gade Institute, University of Bergen, The Laboratory Building, Haukeland University Hospital, N-5021 Bergen, Norway (C.N.); Acquifer AG, Sophienstrasse 136, 76135 Karlsruhe, Germany (J.G.); Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA (X.D.); Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland (A.A.). ; 1] School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK [2] German Cancer Research Center (DKFZ), Genomics & Proteomics Core Facility (GPCF), Im Neuenheimer Feld 580/TP3, Heidelberg 69120, Germany (C.Pr.); Broegelmann Research Laboratory, The Gade Institute, University of Bergen, The Laboratory Building, Haukeland University Hospital, N-5021 Bergen, Norway (C.N.); Acquifer AG, Sophienstrasse 136, 76135 Karlsruhe, Germany (J.G.); Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA (X.D.); Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland (A.A.). ; Erasmus Medical Center, Center for Biomics, Room Ee679b, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. ; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Postfach 3640, 76021 Karlsruhe, Germany. ; 1] Institute of Clinical Sciences and MRC Clinical Sciences Center, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK [2] Department of Informatics, University of Bergen, Thormohlensgate 55, N-5008 Bergen, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531765" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Embryo, Nonmammalian/embryology/metabolism ; Female ; Gene Expression Regulation, Developmental/genetics ; Histones/metabolism ; Methylation ; Mothers ; Nucleosomes/genetics ; Promoter Regions, Genetic/*genetics ; *Transcription Initiation Site ; Transcription Initiation, Genetic ; Transcriptome/genetics ; Zebrafish/embryology/*genetics ; Zygote/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Abstract: As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines and validation methods. We show that using PCR-free methods and increasing sequencing depth to approximately 100 x shows benefits, as long as the tumour:control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artefact-prone nature of the raw data and lack of standards for dealing with the artefacts. However, we show that, using the benchmark mutation set we have created, many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.
    Type of Publication: Journal article published
    PubMed ID: 26647970
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Abstract: The 'Individualized Therapy for Relapsed Malignancies in Childhood' (INFORM) precision medicine study is a nationwide German program for children with high-risk relapsed/refractory malignancies, which aims to identify therapeutic targets on an individualised basis. In a pilot phase, reported here, we developed the logistical and analytical pipelines necessary for rapid and comprehensive molecular profiling in a clinical setting. Fifty-seven patients from 20 centers were prospectively recruited. Malignancies investigated included sarcomas (n = 25), brain tumours (n = 23), and others (n = 9). Whole-exome, low-coverage whole-genome, and RNA sequencing were complemented with methylation and expression microarray analyses. Alterations were assessed for potential targetability according to a customised prioritisation algorithm and subsequently discussed in an interdisciplinary molecular tumour board. Next-generation sequencing data were generated for 52 patients, with the full analysis possible in 46 of 52. Turnaround time from sample receipt until first report averaged 28 d. Twenty-six patients (50%) harbored a potentially druggable alteration with a prioritisation score of 'intermediate' or higher (level 4 of 7). Common targets included receptor tyrosine kinases, phosphoinositide 3-kinase-mammalian target of rapamycin pathway, mitogen-activated protein kinase pathway, and cell cycle control. Ten patients received a targeted therapy based on these findings, with responses observed in some previously treatment-refractory tumours. Comparative primary relapse analysis revealed substantial tumour evolution as well as one case of unsuspected secondary malignancy, highlighting the importance of re-biopsy at relapse. This study demonstrates the feasibility of comprehensive, real-time molecular profiling for high-risk paediatric cancer patients. This extended proof-of-concept, with examples of treatment consequences, expands upon previous personalised oncology endeavors, and presents a model with considerable interest and practical relevance in the burgeoning era of personalised medicine.
    Type of Publication: Journal article published
    PubMed ID: 27479119
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: EXPRESSION ; ALGORITHM ; TOOL ; SITE ; GENE ; GENE-EXPRESSION ; GENOME ; transcription ; ACCURACY ; DNA ; MARKER ; CONTRAST ; SEQUENCE ; SEQUENCES ; FREQUENCY ; FREQUENCIES ; gene expression ; PROMOTER ; DNA methylation ; EVOLUTION ; PARAMETERS ; INVOLVEMENT ; PREDICTION ; specificity ; CLUSTERS ; CPG-ISLANDS ; CLUSTER ; GENOME-WIDE ANALYSIS ; CPG ISLANDS ; CRITERIA ; genomic ; DINUCLEOTIDE ; GENE MARKERS ; TRANSCRIPTION START SITES ; VERTEBRATE GENOMES
    Abstract: Background: Despite their involvement in the regulation of gene expression and their importance as genomic markers for promoter prediction, no objective standard exists for defining CpG islands (CGIs), since all current approaches rely on a large parameter space formed by the thresholds of length, CpG fraction and G+C content. Results: Given the higher frequency of CpG dinucleotides at CGIs, as compared to bulk DNA, the distance distributions between neighboring CpGs should differ for bulk and island CpGs. A new algorithm (CpGcluster) is presented, based on the physical distance between neighboring CpGs on the chromosome and able to predict directly clusters of CpGs, while not depending on the subjective criteria mentioned above. By assigning a p-value to each of these clusters, the most statistically significant ones can be predicted as CGIs. CpGcluster was benchmarked against five other CGI finders by using a test sequence set assembled from an experimental CGI library. CpGcluster reached the highest overall accuracy values, while showing the lowest rate of false-positive predictions. Since a minimum-length threshold is not required, CpGcluster can find short but fully functional CGIs usually missed by other algorithms. The CGIs predicted by CpGcluster present the lowest degree of overlap with Alu retrotransposons and, simultaneously, the highest overlap with vertebrate Phylogenetic Conserved Elements (PhastCons). CpGcluster's CGIs overlapping with the Transcription Start Site (TSS) show the highest statistical significance, as compared to the islands in other genome locations, thus qualifying CpGcluster as a valuable tool in discriminating functional CGIs from the remaining islands in the bulk genome. Conclusion: CpGcluster uses only integer arithmetic, thus being a fast and computationally efficient algorithm able to predict statistically significant clusters of CpG dinucleotides. Another outstanding feature is that all predicted CGIs start and end with a CpG dinucleotide, which should be appropriate for a genomic feature whose functionality is based precisely on CpG dinucleotides. The only search parameter in CpGcluster is the distance between two consecutive CpGs, in contrast to previous algorithms. Therefore, none of the main statistical properties of CpG islands ( neither G+C content, CpG fraction nor length threshold) are needed as search parameters, which may lead to the high specificity and low overlap with spurious Alu elements observed for CpGcluster predictions
    Type of Publication: Journal article published
    PubMed ID: 17038168
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: EXPRESSION ; Germany ; human ; MODEL ; CLASSIFICATION ; GENE ; GENE-EXPRESSION ; GENES ; GENOME ; PROTEIN ; ACCURACY ; TIME ; COMPLEX ; COMPLEXES ; DNA ; TISSUES ; BIOLOGY ; SEQUENCE ; SUSCEPTIBILITY ; PATTERNS ; gene expression ; PROMOTERS ; DNA methylation ; HUMAN GENOME ; bioinformatics ; PREDICTION ; INSIGHTS ; METHYLATION ; MAMMALIAN DEVELOPMENT ; DNA-SEQUENCES ; FEATURES ; CLUSTER-ANALYSIS ; CPG ISLANDS ; VERTEBRATE GENOMES ; biotechnology ; epigenetic ; epigenetic regulation ; WELL ; STRATEGY ; ISLANDS ; FUNCTIONAL-ROLE ; REGIONS TDMS
    Abstract: Background: The computational prediction of DNA methylation has become an important topic in the recent years due to its role in the epigenetic control of normal and cancer-related processes. While previous prediction approaches focused merely on differences between methylated and unmethylated DNA sequences, recent experimental results have shown the presence of much more complex patterns of methylation across tissues and time in the human genome. These patterns are only partially described by a binary model of DNA methylation. In this work we propose a novel approach, based on profile analysis of tissue-specific methylation that uncovers significant differences in the sequences of CpG islands (CGIs) that predispose them to a tissue-specific methylation pattern. Results: We defined CGI methylation profiles that separate not only between constitutively methylated and unmethylated CGIs, but also identify CGIs showing a differential degree of methylation across tissues and cell-types or a lack of methylation exclusively in sperm. These profiles are clearly distinguished by a number of CGI attributes including their evolutionary conservation, their significance, as well as the evolutionary evidence of prior methylation. Additionally, we assess profile functionality with respect to the different compartments of protein coding genes and their possible use in the prediction of DNA methylation. Conclusion: Our approach provides new insights into the biological features that determine if a CGI has a functional role in the epigenetic control of gene expression and the features associated with CGI methylation susceptibility. Moreover, we show that the ability to predict CGI methylation is based primarily on the quality of the biological information used and the relationships uncovered between different sources of knowledge. The strategy presented here is able to predict, besides the constitutively methylated and unmethylated classes, two more tissue specific methylation classes conserving the accuracy provided by leading binary methylation classification methods
    Type of Publication: Journal article published
    PubMed ID: 19383127
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: EXPRESSION ; Drosophila ; CANCER-CELLS ; BIOGENESIS ; SIRNAS ; DICER ; COMPREHENSIVE ANALYSIS ; RNA CLEAVAGE ; PRE-MIRNA ; ARGONAUTE2
    Abstract: MicroRNAs (miRNAs) are key mediators of post-transcriptional gene regulation. The miRNA precursors are processed by the endonucleases Drosha and Dicer into a duplex, bound to an Argonaute protein and unwound into two single-stranded miRNAs. Although alternative ways to generate miRNAs have been discovered, e.g. pre-miRNA cleavage by Ago2 or cleavage products of snoRNAs or tRNAs, all known pathways converge on a double-stranded RNA duplex. Exogenous single-stranded siRNAs (ss-siRNAs) can elicit an effective RNA interference reaction; recent studies have identified chemical modifications increasing their stability and activity. Here, we provide first evidence that endogenous, unmodified, single-stranded RNA sequences are generated from single-stranded loop regions of human pre-miRNA hairpins, the so called loop-miRs. Luciferase assays and immunoprecipitation validate loop-miR activity and incorporation into RNA-induced silencing complexes. This study identifies endogenous miRNAs that are generated from single-stranded regions; hence, it provides evidence that precursor-miRNAs can give rise to three distinct endogenous miRNAs: the guide strand, the passenger strand and the loop-miR.
    Type of Publication: Journal article published
    PubMed ID: 23580554
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: IN-VITRO ; AMPLIFICATION ; EVOLUTION ; DIVERSITY ; POLYMERASE-CHAIN-REACTION ; SELECTION ; DNA-POLYMERASE ; FIDELITY ; ERRORS ; DIELS-ALDERASE RIBOZYME
    Abstract: Catalytic RNAs are attractive objects for studying molecular evolution. To understand how RNA libraries can evolve from randomness toward highly active catalysts, we analyze the original samples that led to the discovery of Diels-Alderase ribozymes by next-generation sequencing. Known structure-activity relationships are used to correlate abundance with catalytic performance. We find that efficient catalysts arose not just from selection for reactivity among the members of the starting library, but from improvement of less potent precursors by mutations. We observe changes in the ribozyme population in response to increasing selection pressure. Surprisingly, even after many rounds of enrichment, the libraries are highly diverse, suggesting that potential catalysts are more abundant in random space than generally thought. To highlight the use of next-generation sequencing as a tool for in vitro selections, we also apply this technique to a recent, less characterized ribozyme selection. Making use of the correlation between sequence evolution and catalytic activity, we predict mutations that improve ribozyme activity and validate them biochemically. Our study reveals principles underlying ribozyme in vitro selections and provides guidelines to render future selections more efficient, as well as to predict the conservation of key structural elements, allowing the rational improvement of catalysts.
    Type of Publication: Journal article published
    PubMed ID: 24157838
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...