Change search
Refine search result
45678910 301 - 350 of 1077
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 301.
    Gautschi, B
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Koller, B.
    Polymorphic microsatellite markers for the goosander (Mergus merganser).2005In: Molecular Ecology Notes, no 5, 133-134 p.Article in journal (Refereed)
  • 302.
    Gavrilets, Sergey
    et al.
    Departments of Ecology and Evolutionary Biology and Mathematics, University of Tennessee, Knoxville,USA.
    Arnqvist, Göran
    Department of Ecology and Environmental Science, University of Umeå, Sweden.
    Friberg, Urban
    Department of Ecology and Environmental Science, University of Umeå, Sweden.
    The evolution of female mate choice by sexual conflict2001In: Proceedings of the Royal Society of London Series B, ISSN 0080-4649, Vol. 268, no 1466, 531-539 p.Article in journal (Refereed)
    Abstract [en]

    Although empirical evidence has shown that many male traits have evolved via sexual selection by female mate choice, our understanding of the adaptive value of female mating preferences is still very incomplete. It has recently been suggested that female mate choice may result from females evolving resistance rather than attraction to males, but this has been disputed. Here, we develop a quantitative genetic model showing that sexual conflict over mating indeed results in the joint evolution of costly female mate choice and exaggerated male traits under a wide range of circumstances. In contrast to traditional explanations of costly female mate choice, which rely on indirect genetic benefits, our model shows that mate choice can be generated as a side–effect of females evolving to reduce the direct costs of mating.

  • 303.
    Ghirlanda, Stefano
    et al.
    Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution. Brooklyn College, USA.
    Enquist, Magnus
    Stockholm University, Faculty of Science, Department of Zoology. Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution.
    Lind, Johan
    Stockholm University, Faculty of Science, Department of Zoology. Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution.
    Coevolution of intelligence, behavioral repertoire, and lifespan2014In: Theoretical Population Biology, ISSN 0040-5809, E-ISSN 1096-0325, Vol. 91, 44-49 p.Article in journal (Refereed)
    Abstract [en]

    Across many taxa, intriguing positive correlations exist between intelligence (measured by proxy as encephalization), behavioral repertoire size, and lifespan. Here we argue, through a simple theoretical model, that such correlations arise from selection pressures for efficient learning of behavior sequences. We define intelligence operationally as the ability to disregard unrewarding behavior sequences, without trying them out, in the search for rewarding sequences. We show that increasing a species' behavioral repertoire increases the number of rewarding behavior sequences that can be performed, but also the time required to learn such sequences. This trade-off results in an optimal repertoire size that decreases rapidly with increasing sequence length. Behavioral repertoire size can be increased by increasing intelligence or lengthening the lifespan, giving rise to the observed correlations between these traits.

  • 304.
    Ghirlanda, Stefano
    et al.
    Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution. Brooklyn College, USA.
    Enquist, Magnus
    Stockholm University, Faculty of Science, Department of Zoology. Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution.
    Lind, Johan
    Stockholm University, Faculty of Science, Department of Zoology. Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution.
    Corrigendum to "Coevolution of intelligence, behavioral repertoire, and lifespan" [Theoret. Popul. Biol. 91 (2014) 44–49]2014In: Theoretical Population Biology, ISSN 0040-5809, E-ISSN 1096-0325, Vol. 97, 57-57 p.Article in journal (Other academic)
  • 305.
    Ghorbani, Abdolbaset
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Saeedi, Yousef
    Shahid Beheshti Univ Med Sci, Tradit Med & Mat Med Res Ctr, Tehran, Iran..
    de Boer, Hugo J.
    Univ Oslo, Nat Hist Museum, Oslo, Norway..
    DNA barcoding in ethnobotany and ethnopharmacology: identifying medicinal plants traded in local markets2015In: Genome, ISSN 0831-2796, E-ISSN 1480-3321, Vol. 58, no 5, 220-220 p.Article in journal (Other academic)
  • 306.
    Glemin, Sylvain
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Arndt, Peter F.
    Messer, Philipp W.
    Petrov, Dmitri
    Galtier, Nicolas
    Duret, Laurent
    Quantification of GC-biased gene conversion in the human genome2015In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 25, no 8, 1215-1228 p.Article in journal (Refereed)
    Abstract [en]

    Much evidence indicates that GC-biased gene conversion (gBGC) has a major impact on the evolution of mammalian genomes. However, a detailed quantification of the process is still lacking. The strength of gBGC can be measured from the analysis of derived allele frequency spectra (DAF), but this approach is sensitive to a number of confounding factors. In particular, we show by simulations that the inference is pervasively affected by polymorphism polarization errors and by spatial heterogeneity in gBGC strength. We propose a new general method to quantify gBGC from DAF spectra, incorporating polarization errors, taking spatial heterogeneity into account, and jointly estimating mutation bias. Applying it to human polymorphism data from the 1000 Genomes Project, we show that the strength of gBGC does not differ between hypermutable CpG sites and non-CpG sites, suggesting that in humans gBGC is not caused by the base-excision repair machinery. Genome-wide, the intensity of gBGC is in the nearly neutral area. However, given that recombination occurs primarily within recombination hotspots, 1%-2% of the human genome is subject to strong gBGC. On average, gBGC is stronger in African than in non-African populations, reflecting differences in effective population sizes. However, due to more heterogeneous recombination landscapes, the fraction of the genome affected by strong gBGC is larger in non-African than in African populations. Given that the location of recombination hotspots evolves very rapidly, our analysis predicts that, in the long term, a large fraction of the genome is affected by short episodes of strong gBGC.

  • 307.
    Goenaga, Julieta
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology. Aarhus Univ, Aarhus Inst Adv Studies, DK-8000 Aarhus C, Denmark..
    Yamane, Takashi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Rönn, Johanna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Arnqvist, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Within-species divergence in the seminal fluid proteome and its effect on male and female reproduction in a beetle2015In: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 15, 266Article in journal (Refereed)
    Abstract [en]

    Background: Male seminal fluid proteins (SFPs), transferred to females during mating, are important reproductive proteins that have multifarious effects on female reproductive physiology and that often show remarkably rapid and divergent evolution. Inferences regarding natural selection on SFPs are based primarily on interspecific comparative studies, and our understanding of natural within-species variation in SFPs and whether this relates to reproductive phenotypes is very limited. Here, we introduce an empirical strategy to study intraspecific variation in and selection upon the seminal fluid proteome. We then apply this in a study of 15 distinct populations of the seed beetle Callosobruchus maculatus. Results: Phenotypic assays of these populations showed significant differences in reproductive phenotypes (male success in sperm competition and male ability to stimulate female fecundity). A quantitative proteomic study of replicated samples of male accessory glands revealed a large number of potential SFPs, of which >= 127 were found to be transferred to females at mating. Moreover, population divergence in relative SFP abundance across populations was large and remarkably multidimensional. Most importantly, variation in male SFP abundance across populations was associated with male sperm competition success and male ability to stimulate female egg production. Conclusions: Our study provides the first direct evidence for postmating sexual selection on standing intraspecific variation in SFP abundance and the pattern of divergence across populations in the seminal fluid proteome match the pattern predicted by the postmating sexual selection paradigm for SFP evolution. Our findings provide novel support for the hypothesis that sexual selection on SFPs is an important engine of incipient speciation.

  • 308.
    Golkar, Siv Österman
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Czene, Stefan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. AstraZeneca R&D, Safety Assessment, Dept Genet Toxicol, AstraZeneca, Södertälje, Sweden.
    Gokarakonda, Amulya
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Intracellular deoxyribonucleotide pool imbalance and DNA damage in cells treated with hydroxyurea, an inhibitor of ribonucleotide reductase2013In: Mutagenesis, ISSN 0267-8357, E-ISSN 1464-3804, Vol. 28, no 6, 653-660 p.Article in journal (Refereed)
    Abstract [en]

    Imbalance in the nucleotide pool of mammalian cells has been shown to result in genotoxic damage. The goal of this study was to devise a sensitive, reproducible and simple method for detection of nucleotide pool changes in mammalian cells that could be used for problem-solving activities in drug development, e.g. mechanistic explanation of a positive response in a mammalian in vitro genotoxicity test. The method evaluated in this study is based on ethanol extraction of the total nucleotide pool, heat treatment and filtration, treatment with calf intestine alkaline phosphatase to convert nucleotides to nucleosides and analysis of the nucleosides by high-performance liquid chromatography with ultraviolet detection. The method was applied to measure the intracellular levels of deoxyribonucleotides in mouse lymphoma (ML) L5178Y cells treated with various concentrations of a model compound, hydroxyurea (HU), a ribonucleotide reductase inhibitor. DNA strand breakage and micronuclei formation were assessed in the same experiments. Imbalance of nucleotide pool (i.e. changes in the relative ratios between individual nucleotide pools) in HU-treated ML cells has been observed already at a concentration of 0.01 mmol/l, whereas genotoxic effects became apparent only at higher concentrations of HU (i.e. 0.25 mmol/l and higher) as indicated by formation of DNA strand breaks and micronuclei.

  • 309.
    Goretti, Daniela
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Department of Biosciences, University of Milan, Via Celoria 26, Milan, Italy.
    Martignago, Damiano
    Landini, Martina
    Brambilla, Vittoria
    Gomez-Ariza, Jorge
    Gnesutta, Nerina
    Galbiati, Francesca
    Collani, Silvio
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Takagi, Hiroki
    Terauchi, Ryohei
    Mantovani, Roberto
    Fornara, Fabio
    Transcriptional and Post-transcriptional Mechanisms Limit Heading Date 1 (Hd1) Function to Adapt Rice to High Latitudes2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 1, e1006530Article in journal (Refereed)
    Abstract [en]

    Rice flowering is controlled by changes in the photoperiod that promote the transition to the reproductive phase as days become shorter. Natural genetic variation for flowering time has been largely documented and has been instrumental to define the genetics of the photoperiodic pathway, as well as providing valuable material for artificial selection of varieties better adapted to local environments. We mined genetic variation in a collection of rice varieties highly adapted to European regions and isolated distinct variants of the long day repressor HEADING DATE 1 (Hd1) that perturb its expression or protein function. Specific variants allowed us to define novel features of the photoperiodic flowering pathway. We demonstrate that a histone fold domain scaffold formed by GRAIN YIELD, PLANT HEIGHT AND HEADING DATE 8 (Ghd8) and several NF-YC subunits can accommodate distinct proteins, including Hd1 and PSEUDO RESPONSE REGULATOR 37 (PRR37), and that the resulting OsNF-Y complex containing Hd1 can bind a specific sequence in the promoter of HEADING DATE 3A (Hd3a). Artificial selection has locally favored an Hd1 variant unable to assemble in such heterotrimeric complex. The causal polymorphism was defined as a single conserved lysine in the CCT domain of the Hd1 protein. Our results indicate how genetic variation can be stratified and explored at multiple levels, and how its description can contribute to the molecular understanding of basic developmental processes.

  • 310. Gottlieb, Bruce
    et al.
    Alvarado, Carlos
    Wang, Chunlin
    Gharizadeh, Baback
    Babrzadeh, Farbod
    Stanford Genome Technology Center, Stanford University, Palo Alto, CA, United States .
    Richards, Brent
    Batist, Gerald
    Basik, Mark
    Beitel, Lenore K.
    Trifiro, Mark
    Making Sense of Intratumor Genetic Heterogeneity: Altered Frequency of Androgen Receptor CAG Repeat Length Variants in Breast Cancer Tissues2013In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 34, no 4, 610-618 p.Article in journal (Refereed)
    Abstract [en]

    To examine the significance of intratumor genetic heterogeneity (ITGH) of the androgen receptor (AR) gene in breast cancer, patient-matched samples of laser capture microdissected breast tumor cells, adjacent normal breast epithelia cells, and peripheral blood leukocytes were sequenced using a novel next generation sequencing protocol. This protocol measured the frequency of distribution of a variable AR CAG repeat length, a functional polymorphism associated with breast cancer risk. All samples exhibited some degree of ITGH with up to 30 CAG repeat length variants identified. Each type of tissue exhibited a different distribution profile of CAG repeat lengths with substantial differences in the frequencies of zero and 1825 CAG AR variants. Tissue differences in the frequency of ARs with each of these CAG repeat lengths were significant as measured by paired, twin t-tests. These results suggest that preferential selection of 1825 CAG repeat length variants in breast tumors may be associated with breast cancer, and support the observation that shorter CAG repeats may protect against breast cancer. They also suggest that merely identifying variant genes will be insufficient to determine the critical mutational events of oncogenesis, which will require measuring the frequency of distribution of mutations within cancerous and matching normal tissues.

  • 311. Gouzi, Jean Y.
    et al.
    Moressis, Anastasios
    Walker, James A.
    Apostolopoulou, Anthi A.
    Palmer, Ruth H.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Bernards, Andre
    Skoulakis, Efthimios M. C.
    The receptor tyrosine kinase alk controls neurofibromin functions in drosophila growth and learning2011In: PLoS Genetics, ISSN 1553-7390, Vol. 7, no 9, e1002281- p.Article in journal (Refereed)
    Abstract [en]

    Anaplastic Lymphoma Kinase (Alk) is a Receptor Tyrosine Kinase (RTK) activated in several cancers, but with largely unknown physiological functions. We report two unexpected roles for the Drosophila ortholog dAlk, in body size determination and associative learning. Remarkably, reducing neuronal dAlk activity increased body size and enhanced associative learning, suggesting that its activation is inhibitory in both processes. Consistently, dAlk activation reduced body size and caused learning deficits resembling phenotypes of null mutations in dNf1, the Ras GTPase Activating Protein-encoding conserved ortholog of the Neurofibromatosis type 1 (NF1) disease gene. We show that dAlk and dNf1 co-localize extensively and interact functionally in the nervous system. Importantly, genetic or pharmacological inhibition of dAlk rescued the reduced body size, adult learning deficits, and Extracellular-Regulated-Kinase (ERK) overactivation dNf1 mutant phenotypes. These results identify dAlk as an upstream activator of dNf1-regulated Ras signaling responsible for several dNf1 defects, and they implicate human Alk as a potential therapeutic target in NF1.

  • 312.
    Goyette, Philippe
    et al.
    Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
    Boucher, Gabrielle
    Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
    Mallon, Dermot
    Department of Surgery, University of Cambridge, Cambridge, UK; National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK.
    Ellinghaus, Eva
    Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.
    Jostins, Luke
    Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK; Christ Church, University of Oxford, St Aldates, UK.
    Huang, Hailiang
    Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
    Ripke, Stephan
    Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
    Gusareva, Elena S.
    Systems and Modeling Unit, Montefiore Institute, University of Liege, Liege, Belgium; Bioinformatics and Modeling, GIGA-R (Groupe Interdisciplinaire de Génoprotéomique Appliquée) Research Center, University of Liege, Liege, Belgium.
    Annese, Vito
    Unit of Gastroenterology, IRCCS-CSS (Istituto di Ricovero e Cura a Carattere Scientifico–Casa Sollievo della Sofferenza) Hospital, San Giovanni Rotondo, Italy; Unit of Gastroenterology SOD2 (Strutture Organizzative Dipartimentali), Azienda Ospedaliero Universitaria (AOU) Careggi, Florence, Italy.
    Hauser, Stephen L.
    Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
    Oksenberg, Jorge R.
    Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
    Thomsen, Ingo
    Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.
    Leslie, Stephen
    Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Mathematics and Statistics, University of Melbourne, Melbourne, Victoria, Australia.
    Daly, Mark J.
    Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
    Van Steen, Kristel
    Systems and Modeling Unit, Montefiore Institute, University of Liege, Liege, Belgium; Bioinformatics and Modeling, GIGA-R (Groupe Interdisciplinaire de Génoprotéomique Appliquée) Research Center, University of Liege, Liege, Belgium.
    Duerr, Richard H.
    Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA.
    Barrett, Jeffrey C.
    Wellcome Trust Sanger Institute, Hinxton, UK.
    McGovern, Dermot P. B.
    Schumm, L. Philip
    Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA.
    Traherne, James A.
    Cambridge Institute for Medical Research, Cambridge, UK; Department of Pathology, University of Cambridge, Cambridge, UK.
    Carrington, Mary N.
    Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA; Ragon Institute of Massachusetts General Hospital, MIT and Harvard, Cambridge, Massachusetts, USA.
    Kosmoliaptsis, Vasilis
    Department of Surgery, University of Cambridge, Cambridge, UK; National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK.
    Karlsen, Tom H.
    Research Institute of Internal Medicine, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
    Franke, Andre
    Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.
    Rioux, John D.
    Research Center, Montreal Heart Institute, Montreal, Quebec, Canada; Faculté de Médecine, Université de Montréal, Montreal, Quebec, Canada.
    High-density mapping of the MHC identifies a shared role for HLA-DRB1*01: 03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis2015In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, no 2, 172-179 p.Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.

  • 313. Greger, Liliana
    et al.
    Su, Jing
    Rung, Johan
    Ferreira, Pedro G
    Lappalainen, Tuuli
    Dermitzakis, Emmanouil T
    Brazma, Alvis
    Tandem RNA chimeras contribute to transcriptome diversity in human population and are associated with intronic genetic variants.2014In: PloS one, ISSN 1932-6203, Vol. 9, no 8, e104567- p.Article in journal (Refereed)
    Abstract [en]

    Chimeric RNAs originating from two or more different genes are known to exist not only in cancer, but also in normal tissues, where they can play a role in human evolution. However, the exact mechanism of their formation is unknown. Here, we use RNA sequencing data from 462 healthy individuals representing 5 human populations to systematically identify and in depth characterize 81 RNA tandem chimeric transcripts, 13 of which are novel. We observe that 6 out of these 81 chimeras have been regarded as cancer-specific. Moreover, we show that a prevalence of long introns at the fusion breakpoint is associated with the chimeric transcripts formation. We also find that tandem RNA chimeras have lower abundances as compared to their partner genes. Finally, by combining our results with genomic data from the same individuals we uncover intronic genetic variants associated with the chimeric RNA formation. Taken together our findings provide an important insight into the chimeric transcripts formation and open new avenues of research into the role of intronic genetic variants in post-transcriptional processing events.

  • 314. Gregers, J.
    et al.
    Green, Henrik
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Division of Drug Research, Department of Medical and Health Sciences, Linköpings Universitet, Linköping, Sweden.
    Christensen, I. J.
    Dalhoff, K.
    Schroeder, H.
    Carlsen, N.
    Rosthoej, S.
    Lausen, B.
    Schmiegelow, K.
    Peterson, C.
    Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia2015In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 15, no 4, 372-379 p.Article in journal (Refereed)
    Abstract [en]

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those eligible. Risk of relapse was increased 2.9-fold for patients with the 1199GA variant versus 1199GG (P = 0.001), and reduced 61% and 40%, respectively, for patients with the 3435CT or 3435TT variants versus 3435CC (overall P = 0.02). The degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P = 0.01/P < 0.0001). We observed more liver toxicity after high-dose methotrexate in patients with 3435CC variant versus 3435CT/TT ( P = 0.03). In conclusion, there is a statistically significant association between ABCB1 polymorphisms, efficacy and toxicity in the treatment of ALL, and ABCB1 1199G > A may be a new possible predictive marker for outcome in childhood ALL.

  • 315.
    Griffin, Robert M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Univ Turku, Dept Biol, Turku 20014, Finland..
    Schielzeth, Holger
    Univ Bielefeld, Dept Evolutionary Biol, D-33615 Bielefeld, Germany.;Friedrich Schiller Univ Jena, Inst Ecol, Dept Populat Ecol, D-07743 Jena, Germany..
    Friberg, Urban
    Linkoping Univ, AVIAN Behav Genom & Physiol Grp, IFM Biol, S-58183 Linkoping, Sweden..
    Autosomal and X-Linked Additive Genetic Variation for Lifespan and Aging: Comparisons Within and Between the Sexes in Drosophila melanogaster2016In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 6, no 12, 3903-3911 p.Article in journal (Refereed)
    Abstract [en]

    Theory makes several predictions concerning differences in genetic variation between the X chromosome and the autosomes due to male X hemizygosity. The X chromosome should: (i) typically show relatively less standing genetic variation than the autosomes, (ii) exhibit more variation in males compared to females because of dosage compensation, and (iii) potentially be enriched with sex-specific genetic variation. Here, we address each of these predictions for lifespan and aging in Drosophila melanogaster. To achieve unbiased estimates of X and autosomal additive genetic variance, we use 80 chromosome substitution lines; 40 for the X chromosome and 40 combining the two major autosomes, which we assay for sex-specific and cross-sex genetic (co)variation. We find significant X and autosomal additive genetic variance for both traits in both sexes (with reservation for X-linked variation of aging in females), but no conclusive evidence for depletion of X-linked variation (measured through females). Males display more X-linked variation for lifespan than females, but it is unclear if this is due to dosage compensation since also autosomal variation is larger in males. Finally, our results suggest that the X chromosome is enriched for sex-specific genetic variation in lifespan but results were less conclusive for aging overall. Collectively, these results suggest that the X chromosome has reduced capacity to respond to sexually concordant selection on lifespan from standing genetic variation, while its ability to respond to sexually antagonistic selection may be augmented.

  • 316. Groenen, M. A.
    et al.
    Archibald, A. L.
    Uenishi, H.
    Tuggle, C. K.
    Takeuchi, Y.
    Rothschild, M. F.
    Rogel-Gaillard, C.
    Park, C.
    Milan, D.
    Megens, H. J.
    Li, S.
    Larkin, D. M.
    Kim, H.
    Frantz, L. A.
    Caccamo, M.
    Ahn, H.
    Aken, B. L.
    Anselmo, A.
    Anthon, C.
    Auvil, L.
    Badaoui, B.
    Beattie, C. W.
    Bendixen, C.
    Berman, D.
    Blecha, F.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Bolund, L.
    Bosse, M.
    Botti, S.
    Bujie, Z.
    Byström, M.
    Capitanu, B.
    Carvalho-Silva, D.
    Chardon, P.
    Chen, C.
    Cheng, R.
    Choi, S. H.
    Chow, W.
    Clark, R. C.
    Clee, C.
    Crooijmans, R. P.
    Dawson, H. D.
    Dehais, P.
    De Sapio, F.
    Dibbits, B.
    Drou, N.
    Du, Z. Q.
    Eversole, K.
    Fadista, J.
    Fairley, S.
    Faraut, T.
    Faulkner, G. J.
    Fowler, K. E.
    Fredholm, M.
    Fritz, E.
    Gilbert, J. G.
    Giuffra, E.
    Gorodkin, J.
    Griffin, D. K.
    Harrow, J. L.
    Hayward, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Howe, K.
    Hu, Z. L.
    Humphray, S. J.
    Hunt, T.
    Hornshoj, H.
    Jeon, J. T.
    Jern, Patric
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jones, M.
    Jurka, J.
    Kanamori, H.
    Kapetanovic, R.
    Kim, J.
    Kim, J. H.
    Kim, K. W.
    Kim, T. H.
    Larson, G.
    Lee, K.
    Lee, K. T.
    Leggett, R.
    Lewin, H. A.
    Li, Y.
    Liu, W.
    Loveland, J. E.
    Lu, Y.
    Lunney, J. K.
    Ma, J.
    Madsen, O.
    Mann, K.
    Matthews, L.
    McLaren, S.
    Morozumi, T.
    Murtaugh, M. P.
    Narayan, J.
    Nguyen, D. T.
    Ni, P.
    Oh, S. J.
    Onteru, S.
    Panitz, F.
    Park, E. W.
    Park, H. S.
    Pascal, G.
    Paudel, Y.
    Perez-Enciso, M.
    Ramirez-Gonzalez, R.
    Reecy, J. M.
    Rodriguez-Zas, S.
    Rohrer, G. A.
    Rund, L.
    Sang, Y.
    Schachtschneider, K.
    Schraiber, J. G.
    Schwartz, J.
    Scobie, L.
    Scott, C.
    Searle, S.
    Servin, B.
    Southey, B. R.
    Sperber, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Stadler, P.
    Sweedler, J. V.
    Tafer, H.
    Thomsen, B.
    Wali, R.
    Wang, J.
    White, S.
    Xu, X.
    Yerle, M.
    Zhang, G.
    Zhang, J.
    Zhao, S.
    Rogers, J.
    Churcher, C.
    Schook, L. B.
    Analyses of pig genomes provide insight into porcine demography and evolution2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 491, no 7424, 393-398 p.Article in journal (Refereed)
    Abstract [en]

    For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.

  • 317. Grogan, Dennis W
    et al.
    Ozarzak, Melissa A
    Bernander, Rolf
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Molecular Evolution.
    Variation in gene content among geographically diverse Sulfolobus isolates2008In: Environmental Microbiology, ISSN 1462-2912, E-ISSN 1462-2920, Vol. 10, no 1, 137-146 p.Article in journal (Refereed)
    Abstract [en]

    The ability of competitive (i.e., comparative) genomic hybridization (CGH) to assess similarity across entire microbial genomes suggests that it should reveal diversification within and between natural populations of free-living prokaryotes. We used CGH to measure relatedness of genomes drawn from Sulfolobus populations that had been shown in a previous study to be diversified along geographical lines. Eight isolates representing a wide range of spatial separation were compared with respect to gene-specific tags based on a closely related reference strain (Sulfolobus solfataricus P2). For the purpose of assessing genetic divergence, 232 loci identified as polymorphic were assigned one of two alleles based on the corresponding fluorescence intensities from the arrays. Clustering of these binary genotypes was stable with respect to changes in the threshold and similarity criteria, and most of the groupings were consistent with an isolation-by-distance model of diversification. These results indicate that increasing spatial separation of geothermal sites correlates not only with minor sequence polymorphisms in conserved genes of Sulfolobus (demonstrated in the previous study), but also with the regions of difference (RDs) that occur between genomes of conspecifics. In view of the abundance of RDs in prokaryotic genomes and the relevance that some RDs may have for ecological adaptation, the results further suggest that CGH on microarrays may have advantages for investigating patterns of diversification in other free-living archaea and bacteria.

  • 318.
    Groth, Petra
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Replication Dynamics in the DNA Damage Response2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Faithful DNA replication is essential and the induction of replication stress may have profound effects on genomic integrity. This is demonstrated by the formation of DNA double strand breaks (DSBs), considered to be the most toxic DNA lesions, at stalled replication forks. Homologous recombination (HR) has been shown to be involved in the replication stress response and has been suggested for stabilisation, restart and repair of stalled replication forks. However, the HR mechanisms induced by replication stress are still, to a major part, unknown. The present thesis focuses on investigating replication patterns following the induction of replication stress. Further, the consequences of stressed replication are studied by detection of DSB formation and characterisation of HR in mammalian cells.

    Here, we have identified WEE1, a regulator of mitotic entry, as a factor required to maintain correct replication. Depletion of WEE1 results in the formation of DSBs specifically in newly replicated DNA, as visualised in a modified pulse field electrophoresis assay. We were also able to detect formation of replication-associated secondary DSBs following treatment with ionizing radiation (IR). These DSBs were further demonstrated as major substrates for IR induced HR.

    Using the DNA fibre technique we investigated the effect of DNA alkylating agents on replication. We found that DNA methylations pose direct physical blocks to progressing replication forks causing them to stall in a checkpoint independent manner. Furthermore, we studied restart kinetics following methylation blocked replication and identified a distinct restart mechanism for blocked replication forks independent of new origin firing and HR.

    In conclusion, our findings increase the knowledge of replication dynamics following perturbed replication and further clarify the role of HR following IR induced damage and DNA alkylation.

  • 319.
    Grube, Martin
    et al.
    Graz university, Austria.
    Gutmann, B.
    Graz university, Austria.
    Arup, Ulf
    Graz university, Austria.
    Rios, A. de los
    Graz university, Austria.
    Mattsson, Jan-Eric
    Uppsala university.
    Wedin, Mats
    Natural History Museum, London.
    An exceptional group I intron-like insertion in SSU rDNA of lichen mycobionts1999In: Current Genetics, ISSN 0172-8083, E-ISSN 1432-0983, Vol. 35, 536-541 p.Article in journal (Refereed)
  • 320. Grundberg, Ida
    et al.
    Kiflemariam, Sara
    Imgenberg-Kreuz, Juliana
    Edlund, Karolina
    Micke, Patrick
    Sundström, Magnus
    Sjöblom, Tobias
    Botling, Johan
    Nilsson, Mats
    In situ mutation detection in cancer tissue sections for research and diagnostics in clinical oncologyArticle in journal (Other academic)
  • 321.
    Gustafsson, Dan
    Linköping University, Department of Physics, Chemistry and Biology, Molecular genetics. Linköping University, The Institute of Technology.
    The origin of naked barley (Hordeum vulgare L. ssp. vulgare) studied bythe nud gene2013Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    The exact origin of the peculiar naked barley is somewhat illusive. There   is a debate whether it has a single, monophyletic origin or a multiple, paraphyletic origin. It is from previous Asian studies on naked   barley known that a mutation   or a deletion of the nud gene expresses the   naked seed phenotype. Not much   investigation has been done outside of   Asia, least of all in the Nordic countries, on what gives naked   barley its character. Therefore this   study was set up to examine if   the Nordic variant of naked barley shares   the same nud allele as the Asian   and thus has a   close connection with it, or   if they have independent mutations. I   could confirm that the known alleles of the nud gene do determine the seed character of barley. Most of the   results of the PCR genotyping confirmed the phenotype of the tested   accessions, both naked and hulled barleys. However, one visually phenotyped naked   barley cultivar (NGB4580) still amplified with the known primers that would   match the Asian hulled allele, meaning that the Nordic accession NGB4580 of   naked barley did not carry the known nud   deletion. This suggests that naked barley has arisen independently in Asia   and in the Nordic countries.

  • 322.
    Gustafsson, Per A
    et al.
    Department of Clinical and Experimental Medicine, Child and Adolescent Psychiatry, Linköping University, Linköping, Sweden.
    Gustafsson, Per E
    Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Sweden.
    Anckarsäter, Henrik
    Department of Neuroscience and Physiology, Forensic Psychiatry, Gothenburg University, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.
    Ljung, Therese
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.
    Nelson, Nina
    Department of Clinical and Experimental Medicine, Department of Pediatrics, Linköping University, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.
    Heritability of cortisol regulation in children2011In: Twin Research and Human Genetics, ISSN 1832-4274, E-ISSN 1839-2628, Vol. 14, no 6, 553-561 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The normal development of cortisol regulation during childhood is thought to be influenced by a complex interplay between environmental and genetic factors.

    METHOD: The aim of this study was to estimate genetic and environmental influences on basal cortisol levels in a sample of 151 twin pairs aged 9-16 years. Salivary cortisol was collected on two consecutive days when the children attended school--immediately after awakening, 30 min post-awakening and at bedtime.

    RESULTS: Heritability was highest (60%) for cortisol levels about 30 min after awakening. For samples taken immediately at awakening heritability was less pronounced (28%) and in the evening low (8%).

    CONCLUSION: The limited genetic influence on evening levels, moderate on cortisol at awakening and high on awakening response, might imply two genetic regulation patterns, one specifically for awakening response and one for the circadian rhythm proper. These findings could explain divergent results in previous studies and highlight the importance of taking the circadian rhythm into account in studies of cortisol levels in children.

  • 323.
    Götherström, Anders
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Anderung, Cecilia
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Hellborg, Linda
    Elburg, Rengert
    Smith, Colin
    Bradley, Dan G
    Ellegren, Hans
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Cattle domestication in the Near East was followed by hybridization with aurochs bulls in Europe.2005In: Proc Biol Sci, ISSN 0962-8452, Vol. 272, no 1579, 2345-50 p.Article in journal (Refereed)
    Abstract [en]

    Domesticated cattle were one of the cornerstones of European Neolithisation and are thought to have been introduced to Europe from areas of aurochs domestication in the Near East. This is consistent with mitochondrial DNA (mtDNA) data, where a clear separation exists between modern European cattle and ancient specimens of British aurochsen. However, we show that Y chromosome haplotypes of north European cattle breeds are more similar to haplotypes from ancient specimens of European aurochsen, than to contemporary cattle breeds from southern Europe and the Near East. There is a sharp north-south gradient across Europe among modern cattle breeds in the frequencies of two distinct Y chromosome haplotypes; the northern haplotype is found in 20 out of 21 European aurochsen or early domestic cattle dated 9500-1000 BC. This indicates that local hybridization with male aurochsen has left a paternal imprint on the genetic composition of modern central and north European breeds. Surreptitious mating between aurochs bulls and domestic cows may have been hard to avoid, or may have occurred intentionally to improve the breeding stock. Rather than originating from a few geographical areas only, as indicated by mtDNA, our data suggest that the origin of domestic cattle may be far more complex than previously thought.

  • 324. Günther, Torsten
    et al.
    Gawenda, Inka
    Schmid, Karl J
    phenosim--A software to simulate phenotypes for testing in genome-wide association studies.2011In: BMC bioinformatics, ISSN 1471-2105, Vol. 12, 265- p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is a great interest in understanding the genetic architecture of complex traits in natural populations. Genome-wide association studies (GWAS) are becoming routine in human, animal and plant genetics to understand the connection between naturally occurring genotypic and phenotypic variation. Coalescent simulations are commonly used in population genetics to simulate genotypes under different parameters and demographic models.

    RESULTS: Here, we present phenosim, a software to add a phenotype to genotypes generated in time-efficient coalescent simulations. Both qualitative and quantitative phenotypes can be generated and it is possible to partition phenotypic variation between additive effects and epistatic interactions between causal variants. The output formats of phenosim are directly usable as input for different GWAS tools. The applicability of phenosim is shown by simulating a genome-wide association study in Arabidopsis thaliana.

    CONCLUSIONS: By using the coalescent approach to generate genotypes and phenosim to add phenotypes, the data sets can be used to assess the influence of various factors such as demography, genetic architecture or selection on the statistical power of association methods to detect causal genetic variants under a wide variety of population genetic scenarios. phenosim is freely available from the authors' website http://evoplant.uni-hohenheim.de.

  • 325.
    Günther, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genes mirror migrations and cultures in prehistoric Europe - a population genomic perspective2016In: Current Opinion in Genetics and Development, ISSN 0959-437X, E-ISSN 1879-0380, Vol. 41, 115-123 p.Article, review/survey (Refereed)
    Abstract [en]

    Genomic information from ancient human remains is beginning to show its full potential for learning about human prehistory. We review the last few years' dramatic finds about European prehistory based on genomic data from humans that lived many millennia ago and relate it to modern-day patterns of genomic variation. The early times, the Upper Paleolithic, appears to contain several population turn-overs followed by more stable populations after the Last Glacial Maximum and during the Mesolithic. Some 11 000 years ago the migrations driving the Neolithic transition start from around Anatolia and reach the north and the west of Europe millennia later followed by major migrations during the Bronze Age. These findings show that culture and lifestyle were major determinants of genomic differentiation and similarity in pre-historic Europe rather than geography as is the case today.

  • 326. Günther, Torsten
    et al.
    Schmitt, Armin O
    Bortfeldt, Ralf H
    Hinney, Anke
    Hebebrand, Johannes
    Brockmann, Gudrun A
    Where in the genome are significant single nucleotide polymorphisms from genome-wide association studies located?2011In: Omics, ISSN 1536-2310, E-ISSN 1557-8100, Vol. 15, no 7-8, 507-12 p.Article in journal (Refereed)
    Abstract [en]

    Recent technological progress has permitted the efficient performance of genome-wide association studies (GWAS) to map genetic variants associated with common diseases. Here, we analyzed 2,893 single nucleotide polymorphisms (SNPs) that have been identified in 593 published GWAS as associated with a disease phenotype with respect to their genomic location. In absolute numbers, most significant SNPs are located in intergenic regions and introns. When compared to their representation on the chips, there is essentially overrepresentation of nonsynonymous coding SNPs (nsSNPs), synonymous coding SNPs, and SNPs in untranscribed regions upstream of genes among the disease associated SNPs. A Gene Ontology term analysis showed that genes putatively causing a phenotype often code for membrane associated proteins or signal transduction genes.

  • 327.
    Hackett, Jamie A.
    et al.
    University of Edinburgh, Western General Hospital, UK.
    Reddington, James P.
    University of Edinburgh, Western General Hospital, UK.
    Nestor, Colm E.
    University of Edinburgh, Western General Hospital, UK.
    Dunican, Donncha S.
    University of Edinburgh, Western General Hospital, UK.
    Branco, Miguel R.
    Babraham Institute, Cambridge and University of Cambridge, UK.
    Reichmann, Judith
    University of Edinburgh, Western General Hospital, UK.
    Reik, Wolf
    Babraham Institute, Cambridge and University of Cambridge, UK.
    Surani, M. Azim
    University of Cambridge, UK.
    Adams, Ian R
    University of Edinburgh, Western General Hospital, UK.
    Meehan, Richard R
    University of Edinburgh, Western General Hospital, UK.
    Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline2012In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 139, no 19, 3623-3632 p.Article in journal (Refereed)
    Abstract [en]

    Mouse primordial germ cells (PGCs) erase global DNA methylation (5mC) as part of the comprehensive epigenetic reprogramming that occurs during PGC development. 5mC plays an important role in maintaining stable gene silencing and repression of transposable elements (TE) but it is not clear how the extensive loss of DNA methylation impacts on gene expression and TE repression in developing PGCs. Using a novel epigenetic disruption and recovery screen and genetic analyses, we identified a core set of germline-specific genes that are dependent exclusively on promoter DNA methylation for initiation and maintenance of developmental silencing. These gene promoters appear to possess a specialised chromatin environment that does not acquire any of the repressive H3K27me3, H3K9me2, H3K9me3 or H4K20me3 histone modifications when silenced by DNA methylation. Intriguingly, this methylation-dependent subset is highly enriched in genes with roles in suppressing TE activity in germ cells. We show that the mechanism for developmental regulation of the germline genome-defence genes involves DNMT3B-dependent de novo DNA methylation. These genes are then activated by lineage-specific promoter demethylation during distinct global epigenetic reprogramming events in migratory (~E8.5) and post-migratory (E10.5-11.5) PGCs. We propose that genes involved in genome defence are developmentally regulated primarily by promoter DNA methylation as a sensory mechanism that is coupled to the potential for TE activation during global 5mC erasure, thereby acting as a failsafe to ensure TE suppression and maintain genomic integrity in the germline.

  • 328.
    Hagenblad, Jenny
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Hülskötter, Jennifer
    Norwegian University of Science and Technology, Department of Biology, NO-7491 Trondheim, Norway, 3University of Applied Sciences Bremen, DE-28199 Bremen, Germany.
    Acharya, Kamal Prasad
    Norwegian University of Science and Technology, Department of Biology, NO-7491 Trondheim, Norway.
    Brunet, Jörg
    Swedish University of Agricultural Sciences, Southern Swedish Forest Research Centre, SE-230 53 Alnarp, Sweden.
    Chabrerie, Olivier
    Plant Biodiversity Lab, FRE 3498 CNRS, Université de Picardie Jules Verne, FR-80037 Amiens, Cedex, France..
    Cousins, Sara A. O.
    Department of Physical Geography and Quaternary Geology, Stockholm University, SE-106 91 Stockholm, Sweden.
    Dar, Pervaiz A
    Department of Botany, University of Kashmir, Srinagar – 190006, Jammu & Kashmir, India..
    Diekmann, Martin
    Vegetation Ecology and Conservation Biology, Institute of Ecology, University of Bremen, DE-28359 Bremen, Germany.
    De Frenne, Pieter
    Forest & Nature Lab,Ghent University, BE-9090 Melle Gontrode, Belgium..
    Hermy, Martin
    Division Forest, Nature and Landscape, University of Leuven, BE-3001 Leuven, Belgium.
    Jamoneau, Aurélien
    Plant Biodiversity Lab, FRE 3498 CNRS, Université de Picardie Jules Verne, FR-80037 Amiens, Cedex, France..
    Kolb, Annette
    Vegetation Ecology and Conservation Biology, Institute of Ecology, University of Bremen, DE-28359 Bremen, Germany.
    Lemke, Isgard
    Vegetation Ecology and Conservation Biology, Institute of Ecology, University of Bremen, DE-28359 Bremen, Germany.
    Plue, Jan
    Department of Physical Geography and Quaternary Geology, Stockholm University, SE-106 91 Stockholm, Sweden.
    Reshi, Zafar A.
    Department of Botany, University of Kashmir, Srinagar – 190006, Jammu & Kashmir, India..
    Jessen Graae, Bente
    Norwegian University of Science and Technology, Department of Biology, NO-7491 Trondheim, Norway..
    Low genetic diversity despite multipleintroductions of the invasive plant species Impatiens glandulifera in Europe2015In: BMC Genetics, ISSN 1471-2156, Vol. 16, no 103Article in journal (Refereed)
    Abstract [en]

    Background: Invasive species can be a major threat to native biodiversity and the number of invasive plant speciesis increasing across the globe. Population genetic studies of invasive species can provide key insights into theirinvasion history and ensuing evolution, but also for their control. Here we genetically characterise populations ofImpatiens glandulifera, an invasive plant in Europe that can have a major impact on native plant communities. Wecompared populations from the species’ native range in Kashmir, India, to those in its invaded range, along alatitudinal gradient in Europe. For comparison, the results from 39 other studies of genetic diversity in invasivespecies were collated.

    Results: Our results suggest that I. glandulifera was established in the wild in Europe at least twice, from an areaoutside of our Kashmir study area. Our results further revealed that the genetic diversity in invasive populations ofI. glandulifera is unusually low compared to native populations, in particular when compared to other invasivespecies. Genetic drift rather than mutation seems to have played a role in differentiating populations in Europe. Wefind evidence of limitations to local gene flow after introduction to Europe, but somewhat less restrictions in thenative range. I. glandulifera populations with significant inbreeding were only found in the species’ native rangeand invasive species in general showed no increase in inbreeding upon leaving their native ranges. In Europe wedetect cases of migration between distantly located populations. Human activities therefore seem to, at leastpartially, have facilitated not only introductions, but also further spread of I. glandulifera across Europe.

    Conclusions: Although multiple introductions will facilitate the retention of genetic diversity in invasive ranges,widespread invasive species can remain genetically relatively invariant also after multiple introductions. Phenotypicplasticity may therefore be an important component of the successful spread of Impatiens glandulifera across Europe.

  • 329.
    Hagenblad, Jenny
    et al.
    Lund University, Sweden.
    Nordborg, Magnus
    Lund University, Sweden.
    Sequence Variation and Haplotype Structure Surrounding the Flowering Time Locus FRI in Arabidopsis thaliana2002In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 161, no 1, 289-298 p.Article in journal (Refereed)
    Abstract [en]

    Linkage disequilibrium in highly selfing organisms is expected to extend well beyond the scale of individual genes. The pattern of polymorphism in such species must thus be studied over a larger scale. We sequenced 14 short (0.5-1 kb) fragments from a 400-kb region surrounding the flowering time locus FRI in a sample of 20 accessions of Arabidopsis thaliana. The distribution of allele frequencies, as quantified by Tajima’s D, varies considerably over the region and is incompatible with a standard neutral model. The region is characterized by extensive haplotype structure, with linkage disequilibrium decaying over 250 kb. In particular, recombination is evident within 35 kb of FRI in a haplotype associated with a functionally important allele. This suggests that A. thaliana may be highly suitable for linkage disequilibrium mapping.

  • 330.
    Hagenblad, Jenny
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Oliveira, Hugo R
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. CIBIO-Research Centre in Biodiversity and Genetic Resources, Campus Agrário de Vairão. R. Padre Armando Quintas, Vairão, Portugal; Nordiska Museet, Swedish Museum of Cultural History; Stockholm, Sweden.
    Forsberg, Nils E. G.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Leino, Matti W.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Nordiska Museet, Swedish Museum of Cultural History, Stockholm, Sweden.
    Geographical distribution of genetic diversity in Secale landrace and wild accessions2016In: BMC Plant Biology, ISSN 1471-2229, E-ISSN 1471-2229, Vol. 16, no 23Article in journal (Refereed)
    Abstract [en]

    Background: Rye, Secale cereale L., has historically been a crop of major importance and is still a key cereal in manyparts of Europe. Single populations of cultivated rye have been shown to capture a large proportion of the geneticdiversity present in the species, but the distribution of genetic diversity in subspecies and across geographical areasis largely unknown. Here we explore the structure of genetic diversity in landrace rye and relate it to that of wildand feral relatives.Results: A total of 567 SNPs were analysed in 434 individuals from 76 accessions of wild, feral and cultivated rye. Geneticdiversity was highest in cultivated rye, slightly lower in feral rye taxa and significantly lower in the wild S. strictum Presl.and S. africanum Stapf. Evaluation of effects from ascertainment bias suggests underestimation of diversity primarily inS. strictum and S. africanum. Levels of ascertainment bias, STRUCTURE and principal component analyses all supportedthe proposed classification of S. africanum and S. strictum as a separate species from S. cereale. S. afghanicum (Vav.)Roshev, S. ancestrale Zhuk., S. dighoricum(Vav.) Roshev, S. segetale (Zhuk.) Roshev and S. vavilovii Grossh. seemed, incontrast, to share the same gene pool as S. cereale and their genetic clustering was more dependent on geographicalorigin than taxonomic classification. S. vavilovii was found to be the most likely wild ancestor of cultivated rye. Amongcultivated rye landraces from Europe, Asia and North Africa five geographically discrete genetic clusters were identified.These had only limited overlap with major agro-climatic zones. Slash-and-burn rye from the Finnmark area in Scandinaviaformed a distinct cluster with little similarity to other landrace ryes. Regional studies of Northern and South-West Europedemonstrate different genetic distribution patterns as a result of varying cultivation intensity.Conclusions: With the exception of S. strictum and S. africanum different rye taxa share the majority of the geneticvariation. Due to the vast sharing of genetic diversity within the S. cereale clade, ascertainment bias seems to be a lesserproblem in rye than in predominantly selfing species. By exploiting within accession diversity geographic structure can beshown on a much finer scale than previously reported.

  • 331.
    Hagenblad, Jenny
    et al.
    University of Southern California, Los Angeles, USA.
    Tang, Chunlao
    University of Southern California, Los Angeles, USA.
    Molitor, John
    University of Southern California, Los Angeles, USA.
    Werner, Jonathan
    Salk Institute for Biological Studies, La Jolla, California, USA.
    Zhao, Keyan
    University of Southern California, Los Angeles, USA.
    Zheng, Honggang
    University of Southern California, Los Angeles, USA.
    Marjoram, Paul
    University of Southern California, Los Angeles, USA.
    Weigel, Detlef
    Salk Institute for Biological Studies, La Jolla, California, USA.
    Nordborg, Magnus
    University of Southern California, Los Angeles, USA.
    Haplotype Structure and Phenotypic Associations in the Chromosomal Regions Surrounding Two Arabidopsis thaliana Flowering Time Loci2004In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 168, no 3, 1627-1638 p.Article in journal (Refereed)
    Abstract [en]

    The feasibility of using linkage disequilbrium (LD) to fine-map loci underlying natural variation in Arabidopsis thaliana was investigated by looking for associations between flowering time and marker polymorphism in the genomic regions containing two candidate genes, FRI and FLC, both of which are known to contribute to natural variation in flowering. A sample of 196 accessions was used, and polymorphism was assessed by sequencing a total of 17 roughly 500-bp fragments. Using a novel Bayesian algorithm based on haplotype similarity, we demonstrate that LD could have been used to fine-map the FRI gene to a roughly 30-kb region and to identify two common loss-of-function alleles. Interestingly, because of genetic heterogeneity, simple single-marker associations would not have been able to map FRI with nearly the same precision. No clear evidence for previously unknown alleles at either locus was found, but the effect of population structure in causing false positives was evident.

  • 332.
    Hailer, F
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Gautschi, B
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Biology. Evolutionsbiologi.
    Helander, B
    Development and multiplex PCR amplification of nove microsatellite markers in the white-tailed sea eagle, Haliaeetus albicilla (Aves: Falconiformes, Accipitridae)2005In: Molecular Ecology Notes, no 5, 938-940 p.Article in journal (Refereed)
  • 333.
    Hall, David
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå Plant Science Centre, Department of Forest Genetics and Plant PhysiologySwedish University of Agricultural Sciences, Umeå, Sweden.
    Hallingbäck, Henrik R.
    Wu, Harry X.
    Estimation of number and size of QTL effects in forest tree traits2016In: Tree Genetics & Genomes, ISSN 1614-2942, E-ISSN 1614-2950, Vol. 12, no 6, 110Article in journal (Refereed)
    Abstract [en]

    Mapping the genetic architecture of forest tree traits is important in order to understand the evolutionary forces that have shaped these traits and to facilitate the development of genomic-based breeding strategies. We examined the number, size, and distribution of allelic effects influencing eight types of traits using 30 published mapping studies (linkage and association mapping) in forest trees. The sizes of allelic effects, measured as the phenotypic variance explained, generally showed a severely right-skewed distribution. We estimated the numbers of underlying causal effects (n(qtl)) for different trait categories by improving a method previously developed by Otto and Jones (Genetics 156: 2093-2107, 2000). Estimates of n(qtl) based on association mapping studies were generally higher (median at 643) than those based on linkage mapping (median at 33). Comparisons with simulated linkage and association mapping data suggested that the lower n(qtl) estimates for the linkage mapping studies could partly be explained by fewer causal loci segregating within the full-sib family populations normally used, but also by the cosegregation of causal loci due to limited recombination. Disease resistance estimates based on linkage mapping studies had the lowest median of four underlying effects, while growth traits based on association mapping had about 580 effects. Theoretically, the capture of 50% of the genetic variation would thus require a population size of about 200 for disease resistance in linkage mapping, while growth traits in association mapping would require about 25,000. The adequacy and reliability of the improved method was successfully verified by applying it to the simulated data.

  • 334.
    Hall, David
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Ma, Xiao-Fei
    Program in Evolutionary Functional Genomics, Evolutionary Biology Center, Uppsala University.
    Ingvarsson, Pär K
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Adaptive evolution of the Populus tremula photoperiod pathway2011In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 20, no 7, 1463-1474 p.Article in journal (Refereed)
    Abstract [en]

    Environmental cues entrain the circadian clock, a core component of the photoperiod pathway in plants, to daily and seasonal changes. The circadian clock mediates input signals from light and temperature receptors to downstream target genes through feedback loops. Several studies have shown that a correct timing of the circadian system is a fitness advantage and genes in photoperiod network have been implied to evolve in response to the diversifying selection in heterogeneous environment. In an attempt to quantify the extent of the historical patterns of selection on genes in the photoperiod pathway in the widely distributed tree species European aspen (Populus tremula) we obtained sequences for twenty-five of the genes in the network and these genes were compared to patterns of nucleotide diversity in 77 randomly chosen genes from across the genome of P. tremula. We found a significant reduction in synonymous diversity in photoperiod genes while non-synonymous diversity was in line with data from control genes. A substantial fraction of the genes show signs of selection, with eight genes showing signs of rapid protein evolution. In contrast to our expectations, genes closely associated with the core circadian clock show rapid protein evolution despite their central position in the pathway. Furthermore, selection on non-synonymous mutations is negatively correlated with synonymous diversity across all genes, indicating the action of recurrent selective sweeps.

  • 335.
    Hambäck, Peter A.
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Weingartner, Elisabet
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Ericson, Lars
    Fors, Lisa
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Cassel-Lundhagen, Anna
    Stenberg, Johan A.
    Bergsten, Johannes
    Bayesian species delimitation reveals generalist and specialist parasitic wasps on Galerucella beetles (Chrysomelidae): sorting by herbivore or plant host2013In: BMC Evolutionary Biology, ISSN 1471-2148, Vol. 13, 92Article in journal (Refereed)
    Abstract [en]

    Background: To understand the ecological and evolutionary consequences of species interactions in food webs necessitates that interactions are properly identified. Genetic analyses suggest that many supposedly generalist parasitoid species should rather be defined as multiple species with a more narrow diet, reducing the probability that such species may mediate indirect interactions such as apparent competition among hosts. Recent studies showed that the parasitoid Asecodes lucens mediate apparent competition between two hosts, Galerucella tenella and G. calmariensis, affecting both interaction strengths and evolutionary feedbacks. The same parasitoid was also recorded from other species in the genus Galerucella, suggesting that similar indirect effects may also occur for other species pairs. Methods: To explore the possibility of such interactions, we sequenced mitochondrial and nuclear genetic markers to resolve the phylogeny of both host and parasitoid and to test the number of parasitoid species involved. We thus collected 139 Galerucella larvae from 8 host plant species and sequenced 31 adult beetle and 108 parasitoid individuals. Results: The analysis of the Galerucella data, that also included sequences from previous studies, verified the five species previously documented as reciprocally monophyletic, but the Bayesian species delimitation for A. lucens suggested 3-4 cryptic taxa with a more specialised host use than previously suggested. The gene data analyzed under the multispecies coalescent model allowed us to reconstruct the species tree phylogeny for both host and parasitoid and we found a fully congruent coevolutionary pattern suggesting that parasitoid speciation followed upon host speciation. Conclusion: Using multilocus sequence data in a Bayesian species delimitation analysis we propose that hymenopteran parasitoids of the genus Asecodes that infest Galerucella larvae constitute at least three species with narrow diet breath. The evolution of parasitoid Asecodes and host Galerucella show a fully congruent coevolutionary pattern. This finding strengthens the hypothesis that the parasitoid in host search uses cues of the host rather than more general cues of both host and plant.

  • 336.
    Hannuksela, Matias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Klar, Joakim
    Ameur, Adam
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sorensen, Karen
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A novel variant in MYLK causes thoracic aortic dissections: genotypic and phenotypic description2016In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 17, 61Article in journal (Refereed)
    Abstract [en]

    Background: Mutations in MYLK cause non- syndromic familial thoracic aortic aneurysms and dissections (FTAAD). Very little is known about the phenotype of affected families. We sought to characterize the aortic disease and the presence of other vascular abnormalities in FTAAD caused by a deletion in MYLK and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers.

    Methods: We studied FTAAD in a 5-generation family that included 19 living members. Exome sequencing was performed to identify the underlying gene defect. Aortic elastic properties measured by TTE, MRI and pulse wave velocity were then compared between mutation carriers and non-carriers.

    Results: Exome sequencing led to the identification of a 2-bp deletion in MYLK (c3272_ 3273del, p. Ser1091*) that led to a premature stop codon and nonsense-mediated decay. Eleven people were mutation carriers and eight people were non-carriers. Five aortic ruptures or dissections occurred in this family, with two survivors. There were no differences in aortic diameter or stiffness between carriers and non-carriers of the mutation.

    Conclusions: Individuals carrying this deletion in MYLK have a high risk of presenting with an acute aortic dissection or rupture. Aortic events occur over a wide range of ages and are not always preceded by obvious aortic dilatation. Aortic elastic properties do not differ between carriers and non-carriers of this mutation, rendering it uncertain whether and when carriers should undergo elective prophylactic surgery.

  • 337. Hao, Limin
    et al.
    Johnsen, Robert
    Lauter, Gilbert
    Södertörn University, School of Life Sciences. Karolinska Institute.
    Baillie, David
    Bürglin, Thomas R.
    Södertörn University, School of Life Sciences. Karolinska Institute.
    Comprehensive analysis of gene expression patterns of hedgehog-related genes2006In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 7, 280- p.Article in journal (Refereed)
    Abstract [en]

    Background: The Caenorhabditis elegans genome encodes ten proteins that share sequence similarity with the Hedgehog signaling molecule through their C-terminal autoprocessing Hint/Hog domain. These proteins contain novel N-terminal domains, and C. elegans encodes dozens of additional proteins containing only these N-terminal domains. These gene families are called warthog, groundhog, ground-like and quahog, collectively called hedgehog (hh)-related genes. Previously, the expression pattern of seventeen genes was examined, which showed that they are primarily expressed in the ectoderm. Results: With the completion of the C. elegans genome sequence in November 2002, we reexamined and identified 61 hh-related ORFs. Further, we identified 49 hh-related ORFs in C. briggsae. ORF analysis revealed that 30% of the genes still had errors in their predictions and we improved these predictions here. We performed a comprehensive expression analysis using GFP fusions of the putative intergenic regulatory sequence with one or two transgenic lines for most genes. The hh-related genes are expressed in one or a few of the following tissues: hypodermis, seam cells, excretory duct and pore cells, vulval epithelial cells, rectal epithelial cells, pharyngeal muscle or marginal cells, arcade cells, support cells of sensory organs, and neuronal cells. Using time-lapse recordings, we discovered that some hh-related genes are expressed in a cyclical fashion in phase with molting during larval development. We also generated several translational GFP fusions, but they did not show any subcellular localization. In addition, we also studied the expression patterns of two genes with similarity to Drosophila frizzled, T23D8.1 and F27E11.3A, and the ortholog of the Drosophila gene dally-like, gpn-1, which is a heparan sulfate proteoglycan. The two frizzled homologs are expressed in a few neurons in the head, and gpn-1 is expressed in the pharynx. Finally, we compare the efficacy of our GFP expression effort with EST, OST and SAGE data. Conclusion: No bona-fide Hh signaling pathway is present in C. elegans. Given that the hh-related gene products have a predicted signal peptide for secretion, it is possible that they constitute components of the extracellular matrix (ECM). They might be associated with the cuticle or be present in soluble form in the body cavity. They might interact with the Patched or the Patched-related proteins in a manner similar to the interaction of Hedgehog with its receptor Patched.

  • 338.
    Hartfield, Matthew
    et al.
    Univ Toronto, Dept Ecol & Evolut Biol, Toronto, ON M5S 3B2, Canada.;Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark..
    Bataillon, Thomas
    Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark..
    Glemin, Sylvain
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution. Univ Montpellier, CNRS, EPHE, Inst Sci Evolut,IRD,ISEM,UMR 5554, Pl Eugene Bataillon, F-34075 Montpellier, France.
    The Evolutionary Interplay between Adaptation and Self-Fertilization2017In: Trends in Genetics, ISSN 0168-9525, E-ISSN 1362-4555, Vol. 33, no 6, 420-431 p.Article, review/survey (Refereed)
    Abstract [en]

    Genome-wide surveys of nucleotide polymorphisms, obtained from next-generation sequencing, have uncovered numerous examples of adaptation in self-fertilizing organisms, especially regarding changes to climate, geography, and reproductive systems. Yet existing models for inferring attributes of adaptive mutations often assume idealized outcrossing populations, which risks mis-characterizing properties of these variants. Recent theoretical work is emphasizing how various aspects of self-fertilization affects adaptation, yet empirical data on these properties are lacking. We review theoretical and empirical studies demonstrating how self-fertilization alters the process of adaptation, illustrated using examples from current sequencing projects. We propose ideas for how future research can more accurately quantify aspects of adaptation in self-fertilizers, including incorporating the effects of standing variation, demographic history, and polygenic adaptation.

  • 339.
    Hartfield, Matthew
    et al.
    CNRS, Inst Rech Dev 224, UM1, UM2,UMR 5290,Lab Malad Infect & Vecteurs Ecol Gen, F-34394 Montpellier 05, France.;Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON M5S 3B2, Canada.;Univ Aarhus, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark..
    Glemin, Sylvain
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution. CNRS, Inst Sci Evolut Montpellier, UMR 5554, F-34095 Montpellier 5, France..
    Limits to Adaptation in Partially Selfing Species2016In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 203, no 2, 959-+ p.Article in journal (Refereed)
    Abstract [en]

    In outcrossing populations, "Haldane's sieve" states that recessive beneficial alleles are less likely to fix than dominant ones, because they are less exposed to selection when rare. In contrast, selfing organisms are not subject to Haldane's sieve and are more likely to fix recessive types than outcrossers, as selfing rapidly creates homozygotes, increasing overall selection acting on mutations. However, longer homozygous tracts in selfers also reduce the ability of recombination to create new genotypes. It is unclear how these two effects influence overall adaptation rates in partially selfing organisms. Here, we calculate the fixation probability of beneficial alleles if there is an existing selective sweep in the population. We consider both the potential loss of the second beneficial mutation if it has a weaker advantage than the first one, and the possible replacement of the initial allele if the second mutant is fitter. Overall, loss of weaker adaptive alleles during a first selective sweep has a larger impact on preventing fixation of both mutations in highly selfing organisms. Furthermore, the presence of linked mutations has two opposing effects on Haldane's sieve. First, recessive mutants are disproportionally likely to be lost in outcrossers, so it is likelier that dominant mutations will fix. Second, with elevated rates of adaptive mutation, selective interference annuls the advantage in selfing organisms of not suffering from Haldane's sieve; outcrossing organisms are more able to fix weak beneficial mutations of any dominance value. Overall, weakened recombination effects can greatly limit adaptation in selfing organisms.

  • 340.
    Hashemi, M.
    et al.
    Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
    Karami-Tehrani, F.
    Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
    Ghavami, Saeid
    Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada; Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
    Maddika, Subbareddy
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Department of Biochemistry and Medical Genetics,University of Manitoba, Winnipeg, Canada .
    Los, Marek Jan
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada, .
    Adenosine and deoxyadenosine induces apoptosis in oestrogen receptor-positive and -negative human breast cancer cells via the intrinsic pathway2005In: Cell Proliferation, ISSN 0960-7722, E-ISSN 1365-2184, Vol. 38, no 5, 269-285 p.Article in journal (Refereed)
    Abstract [en]

    In this study we have examined the cytotoxic effects of different concentrations of adenosine (Ado) and deoxyadenosine (dAdo) on human breast cancer cell lines. Ado and dAdo alone had little effect on cell cytotoxicity. However, in the presence of adenosine deaminase (ADA) inhibitor, EHNA, adenosine and deoxyadenosine led to significant growth inhibition of cells of the lines tested. Ado/EHNA and dAdo/EHNA-induced cell death was significantly inhibited by NBTI, an inhibitor of nucleoside transport, and 5'-amino-5'-deoxyadenosine, an inhibitor of adenosine kinase, but the effects were not affected by 8-phenyltheophylline, a broad inhibitor of adenosine receptors. The Ado/EHNA combination brought about morphological changes consistent with apoptosis. Caspase-9 activation was observed in MCF-7 and MDA-MB468 human breast cancer cell lines on treatment with Ado/EHNA or dAdo/EHNA, but, as expected, caspase-3 activation was only observed in MDA-MB468 cells. The results of the study, thus, suggest that extracellular adenosine and deoxyadenosine induce apoptosis in both oestrogen receptor-positive (MCF-7) and also oestrogen receptor-negative (MDA-MB468) human breast cancer cells by its uptake into the cells and conversion to AMP (dAMP) followed by activation of nucleoside kinase, and finally by the activation of the mitochondrial/intrinsic apoptotic pathway.

  • 341.
    Hasmats, Johanna
    et al.
    Stockholm University, Science for Life Laboratory (SciLifeLab). Kungl. Tekniska högskolan, Sverige.
    Green, Henrik
    Stockholm University, Science for Life Laboratory (SciLifeLab). Kungl. Tekniska högskolan, Sverige.
    Orear, Cedric
    Validire, Pierre
    Huss, Mikael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Käller, Max
    Stockholm University, Science for Life Laboratory (SciLifeLab). Kungl. Tekniska högskolan, Sverige.
    Lundeberg, Joakim
    Stockholm University, Science for Life Laboratory (SciLifeLab). Kungl. Tekniska högskolan, Sverige.
    Assessment of Whole Genome Amplification for Sequence Capture and Massively Parallel Sequencing2014In: PLoS ONE, ISSN 1932-6203, Vol. 9, no 1, e84785- p.Article in journal (Refereed)
    Abstract [en]

    Exome sequence capture and massively parallel sequencing can be combined to achieve inexpensive and rapid global analyses of the functional sections of the genome. The difficulties of working with relatively small quantities of genetic material, as may be necessary when sharing tumor biopsies between collaborators for instance, can be overcome using whole genome amplification. However, the potential drawbacks of using a whole genome amplification technology based on random primers in combination with sequence capture followed by massively parallel sequencing have not yet been examined in detail, especially in the context of mutation discovery in tumor material. In this work, we compare mutations detected in sequence data for unamplified DNA, whole genome amplified DNA, and RNA originating from the same tumor tissue samples from 16 patients diagnosed with non-small cell lung cancer. The results obtained provide a comprehensive overview of the merits of these techniques for mutation analysis. We evaluated the identified genetic variants, and found that most (74%) of them were observed in both the amplified and the unamplified sequence data. Eighty-nine percent of the variations found by WGA were shared with unamplified DNA. We demonstrate a strategy for avoiding allelic bias by including RNA-sequencing information.

  • 342.
    Hasmats, Johanna
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kupershmidt, Ilya
    Edsgärd, Daniel
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    de Petris, Luigi
    Lewensohn, Rolf
    Alexeyenko, Andrey
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Blackhall, Fiona
    Bess, Benjamin
    Lindgren, Andrea
    Sörenson, Sverre
    Brandén, Eva
    Koyi, Hirsh
    Peterson, Curt
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gréen, Henrik
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Using whole exome sequencing to identify genetic candidates for carboplatin and gemcitabine induced toxicitiesArticle in journal (Other academic)
    Abstract [en]

    Chemotherapies are associated with significant inter-individual variability in therapeutic effect and adverse drug reactions. In lung cancer the use of gemcitabine and carboplatin induces grade 3-4 myelosuppression in about ¼ of the patients while an equal fraction of patients are basically unaffected in terms of myelosuppressive side effects. We therefore set out to try to identify genetic markers for gemcitabine / carboplatin induced myelosuppression. We selected 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0-1 after the first chemotherapy cycle) by the chemotherapy out of 243 lung cancer patients treated with gemcitabine / carboplatin. These patients were exome sequenced and their genetic differences compared using six different bioinformatic strategies; whole exome non-synonymous SNV association analysis, deviation from Hardy-Weinberg equilibrium, analysis of genes selected by a priori biological knowledge, analysis of genes selected from gene expression meta-analysis of toxicity data sets, Ingenuity pathway analysis and FunCoup network enrichment analysis. All patients were successfully sequenced and 5000-7000 non-synonymous single nucleotide variants were identified in each patient. PI3 (elastase specific inhibitor in neutrophils) showed the strongest association in the single SNV analysis (nominal p=0.0005). Further, variants within IL37, an inhibitor of the innate immune system, and CSAG1, a tumor antigen, differed among the two patient groups and appeared among the top hits in several of the performed analysis, indicating that the approach identifies genetic variants associated with the immune system and tumor differentiation, which might be important for the sensitivity to chemotherapeutic agents. However, the associations reported here are in a need of replication before clinical interpretations can be made.

  • 343.
    Hasmats, Johanna
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kupershmidt, Ilya
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Rodriguez-Antona, Cristina
    Su, Qiaojuan Jane
    Khan, Muhammad Suleman
    Jara, Carlos
    Mielgo, Xabier
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gréen, Henrik
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Identification of candidate SNPs for drug induced toxicity from differentially expressed genes in associated tissues2012In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 506, no 1, 62-68 p.Article in journal (Refereed)
    Abstract [en]

    The growing collection of publicly available high-throughput data provides an invaluable resource for generating preliminary in silico data in support of novel hypotheses. In this study we used a cross-dataset meta-analysis strategy to identify novel candidate genes and genetic variations relevant to paclitaxel/carboplatin-induced myelosuppression and neuropathy. We identified genes affected by drug exposure and present in tissues associated with toxicity. From ten top-ranked genes 42 non-synonymous single nucleotide polymorphisms (SNPs) were identified in silico and genotyped in 94 cancer patients treated with carboplatin/paclitaxel. We observed variations in 11 SNPs, of which seven were present in a sufficient frequency for statistical evaluation. Of these seven SNPs. three were present in ABCA1 and ATM, and showed significant or borderline significant association with either myelosuppression or neuropathy. The strikingly high number of associations between genotype and clinically observed toxicity provides support for our data-driven computations strategy to identify biomarkers for drug toxicity.

  • 344. Haussler, David
    et al.
    O'Brien, Stephen J.
    Ryder, Oliver A.
    Barker, F. Keith
    Clamp, Michele
    Crawford, Andrew J.
    Hanner, Robert
    Hanotte, Olivier
    Johnson, Warren E.
    McGuire, Jimmy A.
    Miller, Webb
    Murphy, Robert W.
    Murphy, William J.
    Sheldon, Frederick H.
    Sinervo, Barry
    Venkatesh, Byrappa
    Wiley, Edward O.
    Allendorf, Fred W.
    Amato, George
    Baker, C. Scott
    Bauer, Aaron
    Beja-Pereira, Albano
    Bermingham, Eldredge
    Bernardi, Giacomo
    Bonvicino, Cibele R.
    Brenner, Sydney
    Burke, Terry
    Cracraft, Joel
    Diekhans, Mark
    Edwards, Scott
    Ericson, Per G. P.
    Estes, James
    Fjelsda, Jon
    Flesness, Nate
    Gamble, Tony
    Gaubert, Philippe
    Graphodatsky, Alexander S.
    Graves, Jennifer A. Marshall
    Green, Eric D.
    Green, Richard E.
    Hackett, Shannon
    Hebert, Paul
    Helgen, Kristofer M.
    Joseph, Leo
    Kessing, Bailey
    Kingsley, David M.
    Lewin, Harris A.
    Luikart, Gordon
    Martelli, Paolo
    Moreira, Miguel A. M.
    Nguyen, Ngan
    Orti, Guillermo
    Pike, Brian L.
    Rawson, David Michael
    Schuster, Stephan C.
    Seuanez, Hector N.
    Shaffer, H. Bradley
    Springer, Mark S.
    Stuart, Joshua Michael
    Sumner, Joanna
    Teeling, Emma
    Vrijenhoek, Robert C.
    Ward, Robert D.
    Warren, Wesley C.
    Wayne, Robert
    Williams, Terrie M.
    Wolfe, Nathan D.
    Zhang, Ya-Ping
    Graph-Odatsky, Alexander
    Johnson, Warren E.
    Felsenfeld, Adam
    Turner, Steve
    Genome, K. Community Scientists
    Mammals, Grp
    Birds, Grp
    Amphibians Reptiles, Grp
    Fishes, Grp
    General Policy, Grp
    Anal, Grp
    Genome 10K: a proposal to obtain whole-genome sequence for 10 000 vertebrate species2009In: Journal of Heredity, ISSN 0022-1503, E-ISSN 1465-7333, Vol. 100, no 6, 659-674 p.Article in journal (Other academic)
  • 345.
    Hed, Helen
    Umeå University.
    Opportunity for selection during the 17th-19thcenturies in the diocese of Linkoping as estimated with Crow's Index in a population of clergymen's wives1984In: Human Heredity, ISSN 0001-5652, E-ISSN 1423-0062, Vol. 34, no 6, 378-387 p.Article in journal (Refereed)
  • 346.
    Hed, Helen
    Umeå University.
    Opportunity for selection in the parish of Tuna, Sweden.1987In: Human Heredity, ISSN 0001-5652, Vol. 37, no 1, 30-35 p.Article in journal (Refereed)
  • 347.
    Hed, Helen
    Umeå University.
    Selection opportunities in 7 swedish 19TH-century populations1986In: Human Biology, ISSN 0018-7143, E-ISSN 1534-6617, Vol. 58, no 6, 919-931 p.Article in journal (Refereed)
  • 348.
    Hed, Helen
    Umeå University.
    Trends in opportunity for natural selection in the Swedish population during the period 1650-19801987In: Human biology, ISSN 0018-7143, Vol. 59, no 5, 785-797 p.Article in journal (Refereed)
  • 349.
    Hed, Helen M. E.
    Umeå University, Faculty of Science and Technology.
    Opportunity for natural selection in Sweden: a study of childhood mortality and differential reproductivity1986Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Opportunity for natural selection in human populations has so far mainly been studied on anthropological data for tribal populations or on census data for nations. The present study is mainly based on data on individual lifehistories but also, for part of the longitudinal study, on census data. Six of the populations, Nedertorneå, Tuna, Svinnegarn, Trosa, Locknevi and Fleninge are parishes. These sets of data covers the period 1800-1850 as defined by the birthyears of the women. The data for the longitudinal study are derived from two sour­ces, a biography over all clergymen in the diocese of Linköping, cove­ring the period 1600-1845, and material published by the National Swe­dish Central Bureau of Statistics (SCB) that covers the period 1750-1980. For each subpopulation data on childhood mortality and female fertility has been collected and from these data Crow's index of opportunity for natural selection has been calculated. The original index has also been modified in order to estimate the importance of childlessness in relation to the total index.

    The study shows that for the periods and the populations studied, there is a considerable opportunity for natural selection both through mortality and through differential fertility and that, during our cen­tury, differential fertility has become the main asset for natural se­lection, as mortality has been reduced to very low levels. It is also obvious that childlessness is an important factor as regards natural selection in human populations. The cross-sectional study shows signi­ficant differences between the populations for all components of the index. The longitudinal study covers when, the two sets of data are combined, a period of over 350 years, 1600-1980. Over this period changes in index of opportunity for natural selection have occured but these changes are not very drastic as compared to other longitudinal studies. However, within a separate region there can be drastic chang­es in index between decades and there are large differences between regions.

    Mortality and fertility patterns have been studied from different angles. With the exception for the census data, each woman in the stu­dy has be followed from 16 to 40 years of age and each of her children (if any) has be followed from birth to 16 years of age or death, if prior. Therefore it was possible to obtain distributions for age at first childbirth, sibship size, succesful sibship size, childhood mor­tality by age at death, female mortality, and childlessness, total and marital. In some cases a study of sex ratio at birth and at 16 years of age, and birth intervals, have been made. Statistical analysis of the results shows significant differences between populations for all tests that have been applied. The Linköping data was analysed for dif­ferences between periods. Significant differences were found for all of the parameters with the exception of female mortality.

  • 350.
    Hed, Helen
    et al.
    Umeå University.
    Rasmuson, Marianne
    Umeå University.
    Cohort study of Opportunity for selection on 2 Swedish 19th-century parishes with a survey of other estimates1981In: Human Heredity, ISSN 0001-5652, E-ISSN 1423-0062, Vol. 31, no 2, 78-83 p.Article in journal (Refereed)
45678910 301 - 350 of 1077
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf