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  • 301. Dudgeon, Crissy
    et al.
    Shreeram, Sathyavageeswaran
    Tanoue, Kan
    Mazur, Sharlyn J
    Sayadi, Ahmed
    Institute of Molecular and Cell Biology; Proteos; Singapore.
    Robinson, Robert C
    Appella, Ettore
    Bulavin, Dmitry V
    Genetic variants and mutations of PPM1D control the response to DNA damage2013Inngår i: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 12, nr 16Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Wip1 phosphatase is an oncogene that is overexpressed in a variety of primary human cancers. We were interested in identifying genetic variants that could change Wip1 activity. We identified 3 missense SNPs of the human Wip1 phosphatase, L120F, P322Q, and I496V confer a dominant-negative phenotype. On the other hand, in primary human cancers, PPM1D mutations commonly result in a gain-of-function phenotype, leading us to identify a hot-spot truncating mutation at position 525. Surprisingly, we also found a significant number of loss-of-function mutations of PPM1D in primary human cancers, both in the phosphatase domain and in the C terminus. Thus, PPM1D has evolved to generate genetic variants with lower activity, potentially providing a better fitness for the organism through suppression of multiple diseases. In cancer, however, the situation is more complex, and the presence of both activating and inhibiting mutations requires further investigation to understand their contribution to tumorigenesis.

  • 302.
    Dufresnes, Christophe
    et al.
    Univ Lausanne, Lab Conservat Biol, Biophore Bldg, CH-1015 Lausanne, Switzerland; Hintermann & Weber, Ave Alpes 25, CH-1820 Montreux, Switzerland.
    Mazepa, Glib
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi. Univ Lausanne, Dept Ecol & Evolut, Biophore Bldg, CH-1015 Lausanne, Switzerland.
    Jablonski, Daniel
    Comenius Univ, Dept Zool, Ilkovicova 6, Bratislava 84215, Slovakia.
    Oliveira, Ricardo Caliari
    Katholieke Univ Leuven, Zool Inst, Lab Socioecol & Social Evolut, Naamsestr 59, B-3000 Leuven, Belgium.
    Wenseleers, Tom
    Katholieke Univ Leuven, Zool Inst, Lab Socioecol & Social Evolut, Naamsestr 59, B-3000 Leuven, Belgium.
    Shabanov, Dmytro A.
    Kharkov Natl Univ, Dept Zool & Anim Ecol, Svobody Sq 4, UA-61022 Kharkov, Ukraine.
    Auer, Markus
    Senckenberg Nat Hist Collect Dresden, Museum Zool, Konigsbrucker Landstr 159, D-01109 Dresden, Germany.
    Ernst, Raffael
    Senckenberg Nat Hist Collect Dresden, Museum Zool, Konigsbrucker Landstr 159, D-01109 Dresden, Germany.
    Koch, Claudia
    Leibniz Inst Biodiversitat Tiere, Zoolog Forschungsmuseum Alexander Koenig, Bonn, Germany.
    Ramirez-Chaves, Hector E.
    Univ Caldas, Dept Ciencias Biol, Fac Ciencias Exactas & Nat, Calle 65 26-10, Manizales, Caldas, Colombia;Univ Caldas, Museo Hist Nat, Ctr Museos, Calle 65 26-10, Manizales, Caldas, Colombia.
    Mulder, Kevin Patrick
    Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, CIBIO InBIO, Campus Agr Vairao, P-4485661 Vairao, Portugal; Natl Zool Pk, Smithsonian Conservat Biol Inst, Ctr Conservat Genom, 3001 Connecticut Ave NW, Washington, DC 20008 USA; Natl Museum Nat Hist, Smithsonian Inst, Dept Vertebrate Zool, 10th St & Constitution Ave NW, Washington, DC 20560 USA.
    Simonov, Evgeniy
    Russian Acad Sci, Res Grp Physiol & Genet Hydrobionts, Siberian Branch, Inst Systemat & Ecol Anim, Novosibirsk 630091, Russia; Russian Acad Sci, Siberian Branch, Krasnoyarsk Sci Ctr, Fed Res Ctr,Lab Genom Res & Biotechnol, Krasnoyarsk 660036, Russia.
    Tiutenko, Arthur
    Univ Erlangen Nurnberg, Schlosspl 6, D-91054 Erlangen, Germany.
    Kryvokhyzha, Dmytro
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Wennekes, Paul L.
    Univ Reading, Sch Biol Sci, Plant Syst & Evolut, Philip Lyle Bldg 208, Reading RG6 6LA, Berks, England.
    Zinenko, Oleksandr I.
    Kharkov Natl Univ, Dept Zool & Anim Ecol, Svobody Sq 4, UA-61022 Kharkov, Ukraine; Kharkov Natl Univ, Museum Nat, Trinkler St 8, UA-61058 Kharkov, Ukraine.
    Korshunov, Oleksiy V.
    Kharkov Natl Univ, Dept Zool & Anim Ecol, Svobody Sq 4, UA-61022 Kharkov, Ukraine.
    Al-Johany, Awadh M.
    King Saud Univ, Dept Zool, Riyadh 11451, Saudi Arabia.
    Peregontsev, Evgeniy A.
    Zoocomplex MChJ, Gagarin Vil 14, Tashkent 100149, Uzbekistan.
    Masroor, Rafaqat
    Pakistan Museum Nat Hist, Garden Ave, Islamabad 44000, Pakistan.
    Betto-Colliard, Caroline
    Univ Lausanne, Dept Ecol & Evolut, Biophore Bldg, CH-1015 Lausanne, Switzerland.
    Denoel, Mathieu
    Univ Liege, Freshwater & OCean Sci Unit Res FOCUS, Behav Biol Grp, Lab Fish & Amphibian Ethol, Liege, Belgium.
    Borkin, Leo J.
    Russian Acad Sci, Zool Inst, Dept Herpetol, St Petersburg 199034, Russia.
    Skorinov, Dmitriy V.
    Russian Acad Sci, Inst Cytol, St Petersburg, Russia.
    Pasynkova, Roza A.
    Russian Acad Sci, Inst Cytol, St Petersburg, Russia.
    Mazanaeva, Lyudmila F.
    Dagestan State Univ, Makhachkala, Russia.
    Rosanov, Juriy M.
    Russian Acad Sci, Inst Cytol, St Petersburg, Russia.
    Dubey, Sylvain
    Hintermann & Weber, Ave Alpes 25, CH-1820 Montreux, Switzerland; Univ Lausanne, Dept Ecol & Evolut, Biophore Bldg, CH-1015 Lausanne, Switzerland; Agrosustain SA, Route Duillier 50, CH-1260 Nyon, Switzerland.
    Litvinchuk, Spartak
    Russian Acad Sci, Inst Cytol, St Petersburg, Russia; Dagestan State Univ, Makhachkala, Russia.
    Fifteen shades of green: The evolution of Bufotes toads revisited2019Inngår i: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 141, artikkel-id 106615Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The radiation of Palearctic green toads (Bufotes) holds great potential to evaluate the role of hybridization in phylogeography at multiple stages along the speciation continuum. With fifteen species representing three ploidy levels, this model system is particularly attractive to examine the causes and consequences of allopoly-ploidization, a prevalent yet enigmatic pathway towards hybrid speciation. Despite substantial efforts, the evolutionary history of this species complex remains largely blurred by the lack of consistency among the corresponding literature. To get a fresh, comprehensive view on Bufotes phylogeography, here we combined genome-wide multilocus analyses (RAD-seq) with an extensive compilation of mitochondrial, genome size, niche modelling, distribution and phenotypic (bioacoustics, morphometrics, toxin composition) datasets, representing hundreds of populations throughout Eurasia. We provide a fully resolved nuclear phylogeny for Bufotes and highlight exceptional cyto-nuclear discordances characteristic of complete mtDNA replacement (in 20% of species), mitochondrial surfing during post-glacial expansions, and the formation of homoploid hybrid populations. Moreover, we traced the origin of several allopolyploids down to species level, showing that all were exclusively fathered by the West Himalayan B. latastii but mothered by several diploid forms inhabiting Central Asian lowlands, an asymmetry consistent with hypotheses on mate choice and Dobzhansky-Muller incompatibilities. Their intermediate call phenotypes potentially allowed for rapid reproductive isolation, while toxin compositions converged towards the ecologically-closest parent. Across the radiation, we pinpoint a stepwise progression of reproductive isolation through time, with a threshold below which hybridizability is irrespective of divergence (< 6My), above which species barely admix and eventually evolve different mating calls (6-10My), or can successfully cross-breed through allopolyploidization (> 15My). Finally, we clarified the taxonomy of Bufotes (including genetic analyses of type series) and formally described two new species, B. cypriensis sp. nov. (endemic to Cyprus) and B. perrini sp. nov. (endemic to Central Asia). Embracing the genomic age, our framework marks the advent of a new exciting era for evolutionary research in these iconic amphibians.

  • 303.
    Eiche, Andrievs
    Stockholms universitet.
    Response to X-rays in Drosophila melanogaster populations with different irradiation backgrounds1973Doktoravhandling, med artikler (Annet vitenskapelig)
  • 304.
    Eisfeldt, J.
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Mårtensson, G.
    KTH.
    Ameur, A.
    Uppsala Univ, Uppsala, Sweden..
    Nilsson, D.
    Karolinska Inst, Stockholm, Sweden..
    Lindstrand, A.
    Karolinska Inst, Stockholm, Sweden..
    Discovery of novel Viking sequences in Swedish genomes2019Inngår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 27, s. 1766-1766Artikkel i tidsskrift (Annet vitenskapelig)
  • 305.
    Eisfeldt, Jesper
    et al.
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Inst, Sci Life Lab, Sci Pk, Solna, Sweden.;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden..
    Mårtensson, Gustaf
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH).
    Ameur, Adam
    Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Nilsson, Daniel
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Inst, Sci Life Lab, Sci Pk, Solna, Sweden.;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden..
    Lindstrand, Anna
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden..
    Discovery of Novel Sequences in 1,000 Swedish Genomes2020Inngår i: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 37, nr 1, s. 18-30Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Novel sequences (NSs), not present in the human reference genome, are abundant and remain largely unexplored. Here, we utilize de novo assembly to study NS in 1,000 Swedish individuals first sequenced as part of the SweGen project revealing a total of 46 Mb in 61,044 distinct contigs of sequences not present in GRCh38. The contigs were aligned to recently published catalogs of Icelandic and Pan-African NSs, as well as the chimpanzee genome, revealing a great diversity of shared sequences. Analyzing the positioning of NS across the chimpanzee genome, we find that 2,807 NS align confidently within 143 chimpanzee orthologs of human genes. Aligning the whole genome sequencing data to the chimpanzee genome, we discover ancestral NS common throughout the Swedish population. The NSs were searched for repeats and repeat elements: revealing a majority of repetitive sequence (56%), and enrichment of simple repeats (28%) and satellites (15%). Lastly, we align the unmappable reads of a subset of the thousand genomes data to our collection of NS, as well as the previously published Pan-African NS: revealing that both the Swedish and Pan-African NS are widespread, and that the Swedish NSs are largely a subset of the Pan-African NS. Overall, these results highlight the importance of creating a more diverse reference genome and illustrate that significant amounts of the NS may be of ancestral origin.

  • 306.
    Eisfeldt, Jesper
    et al.
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Inst, Sci Life Lab, Sci Pk, Solna, Sweden;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
    Mårtensson, Gustaf
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Sci Life Lab, Div Nanobiotechnol,Dept Prot Sci, Stockholm, Sweden.
    Ameur, Adam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nilsson, Daniel
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Inst, Sci Life Lab, Sci Pk, Solna, Sweden;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
    Lindstrand, Anna
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
    Discovery of Novel Sequences in 1,000 Swedish Genomes2020Inngår i: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 37, nr 1, s. 18-30Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Novel sequences (NSs), not present in the human reference genome, are abundant and remain largely unexplored. Here, we utilize de novo assembly to study NS in 1,000 Swedish individuals first sequenced as part of the SweGen project revealing a total of 46 Mb in 61,044 distinct contigs of sequences not present in GRCh38. The contigs were aligned to recently published catalogs of Icelandic and Pan-African NSs, as well as the chimpanzee genome, revealing a great diversity of shared sequences. Analyzing the positioning of NS across the chimpanzee genome, we find that 2,807 NS align confidently within 143 chimpanzee orthologs of human genes. Aligning the whole genome sequencing data to the chimpanzee genome, we discover ancestral NS common throughout the Swedish population. The NSs were searched for repeats and repeat elements: revealing a majority of repetitive sequence (56%), and enrichment of simple repeats (28%) and satellites (15%). Lastly, we align the unmappable reads of a subset of the thousand genomes data to our collection of NS, as well as the previously published Pan-African NS: revealing that both the Swedish and Pan-African NS are widespread, and that the Swedish NSs are largely a subset of the Pan-African NS. Overall, these results highlight the importance of creating a more diverse reference genome and illustrate that significant amounts of the NS may be of ancestral origin.

    Fulltekst (pdf)
    fulltext
  • 307. Eisfeldt, Jesper
    et al.
    Nazaryan-Petersen, Lusine
    Lundin, Johanna Lundin
    Pettersson, Maria
    Nilsson, Daniel
    Wincent, Josephine
    Lieden, Agne
    Vezzi, Francesco
    Wirta, Valteri
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Käller, Max
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Duelund, Tina
    Houssari, Rayan
    Pignata, Laura
    Bak, Mads
    Tommerup, Niels
    Lundberg, Elisabeth Syk
    Tumer, Zeynep
    Lindstrand, Anna
    Whole genome characterization of array defined clustered CNVs reveals two distinct complex rearrangement subclasses generated through either non homologous repair or template switching2017Inngår i: Molecular Cytogenetics, ISSN 1755-8166, E-ISSN 1755-8166, Vol. 10Artikkel i tidsskrift (Annet vitenskapelig)
  • 308. Ek, Weronica
    et al.
    Sahlqvist, Anna-Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet.
    Crooks, Lucy
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Sgonc, Roswitha
    Dietrich, Hermann
    Wick, Georg
    Ekwall, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet.
    Andersson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Carlborg, Örjan
    Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet.
    Kerje, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Mapping QTL affecting a systemic sclerosis-like disorder in a cross between UCD-200 and red jungle fowl chickens2012Inngår i: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 38, nr 2, s. 352-359Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Systemic sclerosis (SSc) or scleroderma is a rare, autoimmune, multi-factorial disease characterized by early microvascular alterations, inflammation, and fibrosis. Chickens from the UCD-200 line develop a hereditary SSc-like disease, showing all the hallmarks of the human disorder, which makes this line a promising model to study genetic factors underlying the disease. A backcross was generated between UCD-200 chickens and its wild ancestor - the red jungle fowl and a genome-scan was performed to identify loci affecting early (21days of age) and late (175days of age) ischemic lesions of the comb. A significant difference in frequency of disease was observed between sexes in the BC population, where the homogametic males were more affected than females, and there was evidence for a protective W chromosome effect. Three suggestive disease predisposing loci were mapped to chromosomes 2, 12 and 14. Three orthologues of genes implicated in human SSc are located in the QTL region on chromosome 2, TGFRB1, EXOC2-IRF4 and COL1A2, as well as CCR8, which is more generally related to immune function. IGFBP3 is also located within the QTL on chromosome 2 and earlier studies have showed increased IGFBP3 serum levels in SSc patients. To our knowledge, this study is the first to reveal a potential genetic association between IGFBP3 and SSc. Another gene with an immunological function, SOCS1, is located in the QTL region on chromosome 14. These results illustrate the usefulness of the UCD-200 chicken as a model of human SSc and motivate further in-depth functional studies of the implicated candidate genes.

  • 309.
    Ekblom, Robert
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Biao, Wang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi. Uppsala Univ, Dept Ecol & Genet, Evolutionary Biol Ctr, Norbyvagen 18D, S-75236 Uppsala, Sweden..
    Development of transcriptome genetic markers for the great snipe (Gallinago media)2017Inngår i: Conservation Genetics Resources, ISSN 1877-7252, E-ISSN 1877-7260, Vol. 9, nr 4, s. 643-645Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We sequenced the transcriptomes of 14 great snipe (Gallinago media) males from the Gavalia study population (central Norway) using Roche 454 technology. The assembled transcriptome sequences (RNA-Seq) was used to identify 140 microsatellite repeat sequences with sufficient flanking sequence information for primer design. In addition several 1000 single nucleotide polymorphisms in the transcriptome were identified, and a small subset of these were verified by independent genotyping.

    Fulltekst (pdf)
    fulltext
  • 310.
    Ekblom, Robert
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Brechlin, Birte
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Persson, Jens
    Swedish Univ Agr Sci, Dept Ecol, Grimso Wildlife Res Stn, Riddarhyttan, Sweden.
    Smeds, Linnea
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Johansson, Malin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Magnusson, Jessica
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Flagstad, Oystein
    Norwegian Inst Nat Res, Trondheim, Norway.
    Ellegren, Hans
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Genome sequencing and conservation genomics in the Scandinavian wolverine population2018Inngår i: Conservation Biology, ISSN 0888-8892, E-ISSN 1523-1739, Vol. 32, nr 6, s. 1301-1312Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genetic approaches have proved valuable to the study and conservation of endangered populations, especially for monitoring programs, and there is potential for further developments in this direction by extending analyses to the genomic level. We assembled the genome of the wolverine (Gulo gulo), a mustelid that in Scandinavia has recently recovered from a significant population decline, and obtained a 2.42 Gb draft sequence representing >85% of the genome and including >21,000 protein-coding genes. We then performed whole-genome resequencing of 10 Scandinavian wolverines for population genomic and demographic analyses. Genetic diversity was among the lowest detected in a red-listed population (mean genome-wide nucleotide diversity of 0.05%). Results of the demographic analyses indicated a long-term decline of the effective population size (N-e) from 10,000 well before the last glaciation to N-e appeared even lower. The genome-wide F-IS level was 0.089 (possibly signaling inbreeding), but this effect was not observed when analyzing a set of highly variable SNP markers, illustrating that such markers can give a biased picture of the overall character of genetic diversity. We found significant population structure, which has implications for population connectivity and conservation. We used an integrated microfluidic circuit chip technology to develop an SNP-array consisting of 96 highly informative markers that, together with a multiplex pre-amplification step, was successfully applied to low-quality DNA from scat samples. Our findings will inform management, conservation, and genetic monitoring of wolverines and serve as a genomic roadmap that can be applied to other endangered species. The approach used here can be generally utilized in other systems, but we acknowledge the trade-off between investing in genomic resources and direct conservation actions.

    Fulltekst (pdf)
    FULLTEXT01
  • 311.
    Ekblom, Robert
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Slate, Jon
    Horsburgh, Gavin J
    Birkhead, Tom
    Burke, Terry
    Comparison between Normalised and Unnormalised 454-Sequencing Libraries for Small-Scale RNA-Seq Studies2012Inngår i: Comparative and functional genomics, ISSN 1531-6912, E-ISSN 1532-6268, Vol. 2012, s. 281693-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Next-generation sequencing of transcriptomes (RNA-Seq) is being used increasingly in studies of nonmodel organisms. Here, we evaluate the effectiveness of normalising cDNA libraries prior to sequencing in a small-scale study of the zebra finch. We find that assemblies produced from normalised libraries had a larger number of contigs but used fewer reads compared to unnormalised libraries. Considerably more genes were also detected using the contigs produced from normalised cDNA, and microsatellite discovery was up to 73% more efficient in these. There was a positive correlation between the detected expression level of genes in normalised and unnormalised cDNA, and there was no difference in the number of genes identified as being differentially expressed between blood and spleen for the normalised and unnormalised libraries. We conclude that normalised cDNA libraries are preferable for many applications of RNA-Seq and that these can also be used in quantitative gene expression studies.

    Fulltekst (pdf)
    Ekblom et al 2012
  • 312.
    Ekblom, Robert
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi, Populationsbiologi.
    Sæther, Stein Are
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi, Populationsbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi, Evolutionsbiologi.
    Grahn, Mats
    Fiske, Peder
    Kålås, John Atle
    Höglund, Jacob
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi, Populationsbiologi.
    Major histocompatibility complex variation and mate choice in a lekking bird, the great snipe (Gallinago media)2004Inngår i: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 13, nr 12, s. 3821-3828Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genes of the major histocompatibility complex (MHC) play a major part in the activation of the vertebrate immune system. In addition, they also appear to function as cues for mate choice. In mammals especially, several kinds of MHC-dependent mate choice have been hypothesized and observed. These include choice of mates that share no or few alleles with the choosing individual, choice of mates with alleles that differ as much as possible from the choosing individual, choice of heterozygous mates, choice of certain genotypes and choice of rare alleles. We investigated these different aspects of mate choice in relation to MHC in a lekking bird species, the great snipe (Gallinago media). We found no evidence for MHC disassortative mating, no preference for males with many MHC alleles and no preference for rare alleles. However, we did find that some allelic lineages were more often found in males with mating success than in males without mating success. Females do not seem to use themselves as references for the MHC-dependent mate choice, rather they seem to prefer males with certain allele types. We speculate that these alleles may be linked to resistance to common parasites.

  • 313.
    Ekblom, Robert
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Wennekes, Paul
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik.
    Horsburgh, Gavin J.
    Burke, Terry
    Characterization of the house sparrow (Passer domesticus) transcriptome: a resource for molecular ecology and immunogenetics2014Inngår i: Molecular Ecology Resources, ISSN 1755-098X, E-ISSN 1755-0998, Vol. 14, nr 3, s. 636-646Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The house sparrow (Passer domesticus) is an important model species in ecology and evolution. However, until recently, genomic resources for molecular ecological projects have been lacking in this species. Here, we present transcriptome sequencing data (RNA-Seq) from three different house sparrow tissues (spleen, blood and bursa). These tissues were specifically chosen to obtain a diverse representation of expressed genes and to maximize the yield of immune-related gene functions. After de novo assembly, 15250 contigs were identified, representing sequence data from a total of 8756 known avian genes (as inferred from the closely related zebra finch). The transcriptome assembly contain sequence data from nine manually annotated MHC genes, including an almost complete MHC class I coding sequence. There were 407, 303 and 68 genes overexpressed in spleen, blood and bursa, respectively. Gene ontology terms related to ribosomal function were associated with overexpression in spleen and oxygen transport functions with overexpression in blood. In addition to the transcript sequences, we provide 327 gene-linked microsatellites (SSRs) with sufficient flanking sequences for primer design, and 3177 single-nucleotide polymorphisms (SNPs) within genes, that can be used in follow-up molecular ecology studies of this ecological well-studied species.

    Fulltekst (pdf)
    fulltext
  • 314.
    Ekhteraei-Tousi, Samaneh
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Lewerentz, Jacob
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Larsson, Jan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Painting of Fourth and the X-Linked 1.688 Satellite in D. melanogaster is Involved in Chromosome-Wide Gene Regulation2020Inngår i: Cells, ISSN 2073-4409, Vol. 9, nr 2, artikkel-id 323Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chromosome-specific regulatory mechanisms provide a model to understand the coordinated regulation of genes on entire chromosomes or on larger genomic regions. In fruit flies, two chromosome-wide systems have been characterized: The male-specific lethal (MSL) complex, which mediates dosage compensation and primarily acts on the male X-chromosome, and Painting of fourth (POF), which governs chromosome-specific regulation of genes located on the 4th chromosome. How targeting of one specific chromosome evolves is still not understood; but repeated sequences, in forms of satellites and transposable elements, are thought to facilitate the evolution of chromosome-specific targeting. The highly repetitive 1.688 satellite has been functionally connected to both these systems. Considering the rapid evolution and the necessarily constant adaptation of regulatory mechanisms, such as dosage compensation, we hypothesised that POF and/or 1.688 may still show traces of dosage-compensation functions. Here, we test this hypothesis by transcriptome analysis. We show that loss of Pof decreases not only chromosome 4 expression but also reduces the X-chromosome expression in males. The 1.688 repeat deletion, Zhr1(Zygotic hybrid rescue), does not affect male dosage compensation detectably; however, Zhr1 in females causes a stimulatory effect on X-linked genes with a strong binding affinity to the MSL complex (genes close to high-affinity sites). Lack of pericentromeric 1.688 also affected 1.688 expression in trans and was linked to the differential expression of genes involved in eggshell formation. We discuss our results with reference to the connections between POF, the 1.688 satellite and dosage compensation, and the role of the 1.688 satellite in hybrid lethality.

    Fulltekst (pdf)
    fulltext
  • 315.
    Ekwall, Karl
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institute.
    Epigenetic control of centromere behavior2007Inngår i: Annual review of genetics / [ed] Allan Campbell, Wyatt W Anderson, Elizabeth W Jones, Palo Atlo: Annual Reviews , 2007, s. 63-81Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    The centromere is the DNA region that ensures genetic stability and is therefore of vital importance. Paradoxically, centromere proteins and centromeric structural domains are conserved despite that fact that centromere DNA sequences are highly variable and are not conserved. Remarkably, heritable states at the centromere can be propagated independent of the underlying centromeric DNA sequences. This review describes the epigenetic mechanisms governing centromere behavior, i.e., the mechanisms that control centromere assembly and propagation. A centromeric histone variant, CenH3, and histone modifications play key roles at centromeric chromatin. Histone modifications and RNA interference are important in assembly of pericentric heterochromatin structures. The molecular machinery that is directly involved in epigenetic control of centromeres is shared with regulation of gene expression. Nucleosome remodeling factors, histone chaperones, histone-modifying enzymes, transcription factors, and even RNA polymerase II itself control epigenetic states at centromeres.

  • 316.
    Ekwall, Karl
    Södertörns högskola, Institutionen för livsvetenskaper.
    Genome-wide analysis of HDAC function2005Inngår i: Trends in Genetics, ISSN 0168-9525, E-ISSN 1362-4555, Vol. 21, nr 11, s. 608-615Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This article focuses on new developments in the genome-wide analysis of histone deacetylase (HDAC) function in yeast. HDACs are highly conserved in many organisms; therefore, their basic functions can be investigated using experimentally tractable model organisms, such as the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. New microarray techniques have enabled the systematic study of HDACs by identifying their direct and indirect gene targets in addition to their physiological functions and enzymatic specificity. These new approaches have already provided new surprising insights into the basic function of HDACs.

  • 317.
    Elisabeth, Ahlgren
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska högskolan.
    Marker generation for Fine Mapping a QTL in the chicken2014Independent thesis Basic level (degree of Bachelor), 10,5 poäng / 16 hpOppgave
    Abstract [en]

    The purpose of this study was to design and test five SNP markers in an inbred chicken cross between Red Junglefowl and domestic White Leghorn of the 8th generation. The markers lie in a region affecting the tonic immobility behaviour which differs significantly between the two species. The markers could be identified by usage of PCR and pyrosequencing. The data obtained were further used in a small scale quantitative trait locus (QTL) analysis. QTL analysis is a statistical method to link phenotypic traits to genotypic data. Four out of five markers could be genotypes and thereby, made it possible to proceed with the QTL analysis. The results showed that there is no QTL associated with the markers identified. The two flanking markers were closest to a significant difference between genotypes and it is therefore a possibility that a QTL lies close further down or up the searched region. From the line map it is indicated that there is little recombination in the marker region.

    Fulltekst (pdf)
    Marker generation for Fine Mapping a QTL in the chicken
  • 318.
    Ellegaard, Kirsten M.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Tamarit, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Javelind, Emelie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Olofsson, Tobias C.
    Andersson, Siv G. E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Vasquez, Alejandra
    Extensive intra-phylotype diversity in lactobacilli and bifidobacteria from the honeybee gut2015Inngår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 16, artikkel-id 284Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In the honeybee Apis mellifera, the bacterial gut community is consistently colonized by eight distinct phylotypes of bacteria. Managed bee colonies are of considerable economic interest and it is therefore important to elucidate the diversity and role of this microbiota in the honeybee. In this study, we have sequenced the genomes of eleven strains of lactobacilli and bifidobacteria isolated from the honey crop of the honeybee Apis mellifera. Results: Single gene phylogenies confirmed that the isolated strains represent the diversity of lactobacilli and bifidobacteria in the gut, as previously identified by 16S rRNA gene sequencing. Core genome phylogenies of the lactobacilli and bifidobacteria further indicated extensive divergence between strains classified as the same phylotype. Phylotype-specific protein families included unique surface proteins. Within phylotypes, we found a remarkably high level of gene content diversity. Carbohydrate metabolism and transport functions contributed up to 45% of the accessory genes, with some genomes having a higher content of genes encoding phosphotransferase systems for the uptake of carbohydrates than any previously sequenced genome. These genes were often located in highly variable genomic segments that also contained genes for enzymes involved in the degradation and modification of sugar residues. Strain-specific gene clusters for the biosynthesis of exopolysaccharides were identified in two phylotypes. The dynamics of these segments contrasted with low recombination frequencies and conserved gene order structures for the core genes. Hits for CRISPR spacers were almost exclusively found within phylotypes, suggesting that the phylotypes are associated with distinct phage populations. Conclusions: The honeybee gut microbiota has been described as consisting of a modest number of phylotypes; however, the genomes sequenced in the current study demonstrated a very high level of gene content diversity within all three described phylotypes of lactobacilli and bifidobacteria, particularly in terms of metabolic functions and surface structures, where many features were strain-specific. Together, these results indicate niche differentiation within phylotypes, suggesting that the honeybee gut microbiota is more complex than previously thought.

    Fulltekst (pdf)
    fulltext
  • 319.
    Ellegaard, Kirsten Maren
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Klasson, Lisa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Näslund, Kristina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bourtzis, Kostas
    Andersson, Siv G. E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Comparative Genomics of Wolbachia and the Bacterial Species Concept2013Inngår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, nr 4, s. e1003381-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The importance of host-specialization to speciation processes in obligate host-associated bacteria is well known, as is also the ability of recombination to generate cohesion in bacterial populations. However, whether divergent strains of highly recombining intracellular bacteria, such as Wolbachia, can maintain their genetic distinctness when infecting the same host is not known. We first developed a protocol for the genome sequencing of uncultivable endosymbionts. Using this method, we have sequenced the complete genomes of the Wolbachia strains wHa and wNo, which occur as natural double infections in Drosophila simulans populations on the Seychelles and in New Caledonia. Taxonomically, wHa belong to supergroup A and wNo to supergroup B. A comparative genomics study including additional strains supported the supergroup classification scheme and revealed 24 and 33 group-specific genes, putatively involved in host-adaptation processes. Recombination frequencies were high for strains of the same supergroup despite different host-preference patterns, leading to genomic cohesion. The inferred recombination fragments for strains of different supergroups were of short sizes, and the genomes of the co-infecting Wolbachia strains wHa and wNo were not more similar to each other and did not share more genes than other A- and B-group strains that infect different hosts. We conclude that Wolbachia strains of supergroup A and B represent genetically distinct clades, and that strains of different supergroups can co-exist in the same arthropod host without converging into the same species. This suggests that the supergroups are irreversibly separated and that barriers other than host-specialization are able to maintain distinct clades in recombining endosymbiont populations. Acquiring a good knowledge of the barriers to genetic exchange in Wolbachia will advance our understanding of how endosymbiont communities are constructed from vertically and horizontally transmitted genes.

    Fulltekst (pdf)
    fulltext
  • 320.
    Ellegren, H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    DNA löser brott med djur.2004Inngår i: Kriminalteknik, nr 3, s. 10-11Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 321.
    Ellegren, H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    Genetisk forskning visar på den framgångsrike hingsten.2004Inngår i: Miljöforskning: (FORMAS), Vol. 2, nr 22-24Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 322.
    Ellegren, H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    Microsatellites: simple sequences with complex evolution.2004Inngår i: Nature Reviews Genetics, nr 5, s. 435-445Artikkel i tidsskrift (Fagfellevurdert)
  • 323.
    Ellegren, H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    Vad är en människa?2004Inngår i: Forsking och framsteg, nr 4, s. 16-Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 324.
    Ellegren, Hans
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    Evolution: Natural selection in the evolution of humans and chimps.2005Inngår i: Curren Biology, nr 22, s. R919-922Artikkel i tidsskrift (Fagfellevurdert)
  • 325.
    Ellegren, Hans
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    The avian genome uncovered.2005Inngår i: Trends in Ecology and Evolution, nr 20, s. 180-186Artikkel i tidsskrift (Fagfellevurdert)
  • 326.
    Ellegren, Hans
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    The dog has its day.2005Inngår i: Nature, nr 438, s. 745-746Artikkel i tidsskrift (Fagfellevurdert)
  • 327.
    Ellegren, Hans
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Galtier, Nicolas
    Univ Montpellier 2, French Natl Ctr Sci Res CNRS, Inst Evolutionary Sci, Pl E Bataillon, F-34095 Montpellier, France..
    Determinants of genetic diversity2016Inngår i: Nature reviews genetics, ISSN 1471-0056, E-ISSN 1471-0064, Vol. 17, nr 7, s. 422-433Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Genetic polymorphism varies among species and within genomes, and has important implications for the evolution and conservation of species. The determinants of this variation have been poorly understood, but population genomic data from a wide range of organisms now make it possible to delineate the underlying evolutionary processes, notably how variation in the effective population size (Ne) governs genetic diversity. Comparative population genomics is on its way to providing a solution to 'Lewontin's paradox' - the discrepancy between the many orders of magnitude of variation in population size and the much narrower distribution of diversity levels. It seems that linked selection plays an important part both in the overall genetic diversity of a species and in the variation in diversity within the genome. Genetic diversity also seems to be predictable from the life history of a species.

  • 328.
    Ellencrona, Ellen
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper.
    Melik, Wessam
    Södertörns högskola, Institutionen för livsvetenskaper.
    Johansson, Magnus
    Södertörns högskola, Institutionen för livsvetenskaper.
    Novel PDZ dependent cell associations of the NS5 proteins of Tick-borne encephalitis virus and West-Nile virusManuskript (preprint) (Annet vitenskapelig)
  • 329.
    Ellencrona, Karin
    Södertörns högskola, Institutionen för livsvetenskaper.
    Functional characterization of interactions between the flavivirus NS5 protein and PDZ proteins of the mammalian host2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Flaviviruses are found all over the world and affect and infect millions of people every year. Flavivirus infection can lead to severe clinical outcomes resulting in neuronal damages e.g. Tick-borne encephalitis virus (TBEV), or severe hemorrhagic fevers e.g. Dengue virus (DENV). In order to effectively treat infected patients and to prevent these diseases we must understand how these viruses work and how they interfere with the mammalian host. This thesis is focusing on interactions between the virus protein NS5 and human host cell proteins. The interactions presented here might be key factors for out-come of viral disease. NS5 is the largest of the non-structural proteins and is essential for the replication and the capping as it contains both RNA dependent RNA polymerase and Methyltransferase domains. We found that TBEV NS5 interacts with human PDZ domain protein Scribble, a polarization protein important e.g. in regulating membrane trafficking. We determined that the interaction depend on a novel internal motif in TBEVNS5. This interaction could be correlated to NS5s ability to interfere with the immune system as absence of Scribble prevented NS5 from blocking phosphorylation of STAT upon Interferon induction. The role of NS5 in human PDZ domain targeting was addressed further by using a PDZ array system. Both TBEVNS5 and DENVNS5 bind additional PDZ domains using the internal motif. The tight junction protein ZO-1 binds both DENVNS5 and TBEVNS5. DENVNS5 is mainly present in the nucleus and co-localize with ZO-1 in un-polarized cells. In polarized cells TBEVNS5 and ZO-1 co-localize at the plasmamembrane. Putative C-terminal PDZ binding motifs of TBEVNS5 and WNVNS5 were characterized using the PDZ array system. This detected four novel binding partners of TBEVNS5 but numerous of potential WNVNS5 binding partners. We found that TBEVNS5 co-localizes with ZO-2 in the cellular membrane. Further, we found that TBEVNS5 induce the AP-1 by a 2 fold over the control.

  • 330.
    Ellencrona, Karin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Functional characterization of interactions between the flavivirus NS5 protein and PDZ proteins of the mammalian host2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Flaviviruses are found all over the world and affect and infect millions of people every year. Flavivirus infection can lead to severe clinical outcomes resulting in neuronal damages e.g. Tick-borne encephalitis virus (TBEV), or severe hemorrhagic fevers e.g. Dengue virus (DENV). In order to effectively treat infected patients and to prevent these diseases we must understand how these viruses work and how they interfere with the mammalian host. This thesis is focusing on interactions between the virus protein NS5 and human host cell proteins. The interactions presented here might be key factors for out-come of viral disease. NS5 is the largest of the non-structural proteins and is essential for the replication and the capping as it contains both RNA dependent RNA polymerase and Methyltransferase domains. We found that TBEV NS5 interacts with human PDZ domain protein Scribble, a polarization protein important e.g. in regulating membrane trafficking. We determined that the interaction depend on a novel internal motif in TBEVNS5. This interaction could be correlated to NS5s ability to interfere with the immune system as absence of Scribble prevented NS5 from blocking phosphorylation of STAT upon Interferon induction. The role of NS5 in human PDZ domain targeting was addressed further by using a PDZ array system. Both TBEVNS5 and DENVNS5 bind additional PDZ domains using the internal motif. The tight junction protein ZO-1 binds both DENVNS5 and TBEVNS5. DENVNS5 is mainly present in the nucleus and co-localize with ZO-1 in un-polarized cells. In polarized cells TBEVNS5 and ZO-1 co-localize at the plasmamembrane. Putative C-terminal PDZ binding motifs of TBEVNS5 and WNVNS5 were characterized using the PDZ array system. This detected four novel binding partners of TBEVNS5 but numerous of potential WNVNS5 binding partners. We found that TBEVNS5 co-localizes with ZO-2 in the cellular membrane. Further, we found that TBEVNS5 induce the AP-1 by a 2 fold over the control.

  • 331.
    Elmberg, Johan
    et al.
    Högskolan Kristianstad, Sektionen för lärande och miljö, Avdelningen för Naturvetenskap. Högskolan Kristianstad, Forskningsmiljön Man & Biosphere Health (MABH).
    Söderquist, Pär
    Högskolan Kristianstad, Forskningsmiljön Man & Biosphere Health (MABH). Högskolan Kristianstad, Sektionen för lärande och miljö, Avdelningen för Naturvetenskap.
    Gunnarsson, Gunnar
    Högskolan Kristianstad, Sektionen för lärande och miljö, Avdelningen för Naturvetenskap. Högskolan Kristianstad, Forskningsmiljön Man & Biosphere Health (MABH).
    Thulin, Carl-Gustaf
    SLU, Umeå.
    Champagnon, Jocelyn
    Frankrike.
    Guillemain, Matthieu
    Frankrike.
    Kreisinger, Jakub
    Tjeckien.
    Prins, H. H. T.
    Nederländerna.
    Crooijmans, R. P. M. A.
    Nederländerna.
    Kraus, R. H. S.
    Tyskland.
    Farmed European mallards are genetically different and cause introgression in the wild population following releases2016Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The practice of restocking already viable populations to increase harvest potential has since long been common in forestry, fisheries and wildlife management. The potential risks of restocking native species have long been overshadowed by the related issue of invasive alien species. However, during the last decade releases of native species with potentially non-native genome have received more attention. A suitable model to study genetic effects of large-scale releases of native species is the Mallard Anas platyrhynchos, being the most widespread duck in the world, largely migratory, and an important quarry species. More than 3 million unfledged hatchlings are released each year around Europe to increase local harvest. The aims of this study were to determine if wild and released farmed Mallards differ genetically, if there are signs of previous or ongoing introgression between wild and farmed birds, and if the genetic structure of the wild Mallard population has changed since large-scale releases started in Europe in the 1970s. Using 360 Single Nucleotide Polymorphisms (SNPs) we found that the genetic structure differed among historical wild, present-day wild, and farmed Mallards in Europe. We also found signs of introgression in the wild Mallard population, that is, individuals with a genetic background of farmed stock are part of the present free-living population. Although only a small proportion of the released Mallards appears to survive to merge with the free-living breeding population, their numbers are still so large that the genetic impact may have significance for the wild population in terms of individual survival and longterm fitness.

  • 332. El-Sayed, Najib M.
    et al.
    Myler, Peter J
    Bartholomeu, Daniella C
    Nilsson, Daniel
    Aggarwal, Gautam
    Tran, Anh-Nhi
    Ghedin, Elodie
    Worthey, Elizabeth A
    Delcher, Arthur L
    Blandin, Gaêlle
    Westenberger, Scott J
    Caler, Elisabet
    Cerqueira, Gustavo C
    Branche, Carole
    Haas, Brian
    Anupama, Atashi
    Arner, Erik
    Aslund, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Attipoe, Philip
    Bontempi, Esteban
    Bringaud, Frederic
    Burton, Peter
    Cadag, Eithon
    Campbell, David A
    Carrington, Mark
    Crabtree, Jonathan
    Darban, Hamid
    da Silveira, Jose Franco
    de Jong, Pieter
    Edwards, Kimberly
    Englund, Paul T
    Fazelina, Gholam
    Feldblyum, Tamara
    Ferella, Marcela
    Frasch, Alberto Carlos
    Gull, Keith
    Horn, David
    Hou, Lihua
    Huang, Yiting
    Kindlund, Ellen
    Klingbeil, Michele
    Kluge, Sindy
    Koo, Hean
    Lacerda, Daniela
    Levin, Mariano J
    Lorenzi, Hernan
    Louie, Tin
    Machado, Carlos Renato
    McCulloch, Richard
    McKenna, Alan
    Mizuno, Yumi
    Mottram, Jeremy C
    Nelson, Siri
    Ochaya, Stephen
    Osoegawa, Kazutoyo
    Pai, Grace
    Parsons, Marilyn
    Pentony, Martin
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Pop, Mihai
    Ramirez, Jose Luis
    Rinta, Joel
    Robertson, Laura
    Salzberg, Steven L
    Sanchez, Daniel O
    Seyler, Amber
    Sharma, Reuben
    Shetty, Jyoti
    Simpson, Anjana J
    Sisk, Ellen
    Tammi, Martti T
    Tarleton, Rick
    Teixeira, Santuza
    Van Aken, Susan
    Vogt, Christy
    Ward, Pauline N
    Wickstead, Bill
    Wortman, Jennifer
    White, Owen
    Fraser, Claire M
    Stuart, Kenneth D
    Andersson, Björn
    The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease.2005Inngår i: Science, ISSN 1095-9203, Vol. 309, nr 5733, s. 409-15Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.

  • 333.
    Emilsson, Lina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik.
    Nilsson, Tatjana
    Cedazo-Minguez, Angel
    Benedikz, Eirikur
    Jazin, Elena
    RGS4: A novel mediator of APP processingManuskript (Annet vitenskapelig)
  • 334.
    Emilsson, Lina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Evolutionsbiologi.
    Saetre, Peter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Evolutionsbiologi.
    Balciuniene, Jorune
    Castensson, Anja
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Evolutionsbiologi.
    Cairns, Nigel
    Jazin, Elena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Evolutionsbiologi.
    Increased monoamine oxidase messenger RNA expression levels in frontal cortex of Alzheimer's disease patients2002Inngår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 326, nr 1, s. 56-60.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia in the industrialised world. The two monoamine oxidase (MAO) enzymes, monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB), are important in the metabolism of monoamine neurotransmitters. AD and ageing have been shown to increase enzyme activity for both MAOA and MAOB. An increase (rather than decrease) of enzyme activity is a rare event in a disease that results in a decrease in the number of cells in the brain. The mechanism, transcriptional or post-transcriptional, responsible for the increase in protein activity, is not known. In this study, we investigate for the first time the messenger RNA (mRNA) expression levels of both MAOA and MAOB in 246 cortical brain samples obtained at autopsy from 62 AD patients and 61 normal controls. We found a significant increase in mRNA levels for both MAOA (P=0.001) and MAOB (P=0.002) in disease brain tissue. This indicates that both MAO enzymes might be important in the progression of AD.

  • 335.
    Emilsson, Lina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Zoologisk utvecklingsbiologi.
    Saetre, Peter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Zoologisk utvecklingsbiologi.
    Jazin, Elena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Zoologisk utvecklingsbiologi.
    Alzheimer’s disease: mRNA expression profiles of multiple patients show alterations of genes involved with calcium signalling2006Inngår i: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 21, nr 3, s. 618-625Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We combined global and high-resolution strategies to find genes with altered mRNA expression levels in one of the largest collection of brain autopsies from Alzheimer's patients and controls ever studied. Our global analysis involved microarray hybridizations of large pools of samples obtained from 114 individuals, using two independent sets of microarrays. Ten genes selected from the microarray experiments were quantified on each individual separately using real-time RT-PCR. This high-resolution analysis accounted for systematic differences in age, postmortem interval, brain pH, and reference gene expression, and it estimated the effect of disease on mRNA levels, on top of the effect of all other variables. Differential expression was confirmed for eight out of ten genes. Among them, Type B inositol 1,4,5-trisphosphate 3-kinase (ITPKB), and regulator of G protein signaling 4 (RGS4) showed highly altered expression levels in patients (P values < 0.0001). Our results point towards increased inositol triphospate (IP3)-mediated calcium signaling in Alzheimer's disease.

  • 336.
    Emma, Lind
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Zoologiska institutionen. Södertörns högskola.
    Ohlin, Helena
    Mälardalens högskola.
    Grahn, Mats
    Södertörns högskola.
    Fine scale genetic structure in Thresspine sticklback (Gasterosteus aculeatus) along Sweden's coastManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    There are three basic types of population structures in marine environments; populations that are distinct, with a continuous change and without any differentiation. In each type the population units are characterized by groups of individuals with panmixia within groups and site fidelity to a limited geographic area. Earlier studies of the population genetic structure on sticklebacks in the Baltic Sea have shown none or only little structure. We have sampled 8 sites (253 individuals) along Sweden’s coast to estimate the genetic structure, using five microsatellites and 173 Amplified Fragment Length Polymorphism (AFLP) markers and detected a fine scale genetic structure (AFLP FST= 25%, microsatellites FST = 2.7%). With AFLPs the observed variation followed isolation by distance model (but not with microsatellites). Even sites separated by only 2 km of water are significantly separated. Both Bayesian clustering analysis and Capscale separated populations and identified populations from Gulf of Bothnia (4 psu) and from the west coast (20 psu) as genetically distinctly different from Baltic populations (about 7-8 psu).  In conclusion, gene flow is limited between sampled sites, and since no geographic barriers can be distinguished the population structure is likely caused by the sticklebacks’ behavior. Hence, we have probably sampled either stationary populations of marine sticklebacks, or homing sticklebacks. In this study AFLP and microsatellites did not give congruent results; with AFLPs we got high separation, and genetic variation followed isolation by distance model and supported the continuous change type of population structure.

  • 337. Engstrom, Karin
    et al.
    Wojdacz, Tomasz K.
    Marabita, Francesco
    Ewels, Philip
    Käller, Max
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Vezzi, Francesco
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Prezza, Nicola
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Gruselius, Joel
    Vahter, Marie
    Broberg, Karin
    Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women2017Inngår i: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 91, nr 5, s. 2067-2078Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Arsenic, a carcinogen with immunotoxic effects, is a common contaminant of drinking water and certain food worldwide. We hypothesized that chronic arsenic exposure alters gene expression, potentially by altering DNA methylation of genes encoding central components of the immune system. We therefore analyzed the transcriptomes (by RNA sequencing) and methylomes (by target-enrichment next-generation sequencing) of primary CD4-positive T cells from matched groups of four women each in the Argentinean Andes, with fivefold differences in urinary arsenic concentrations (median concentrations of urinary arsenic in the lower- and high-arsenic groups: 65 and 276 mu g/l, respectively). Arsenic exposure was associated with genome-wide alterations of gene expression; principal component analysis indicated that the exposure explained 53% of the variance in gene expression among the top variable genes and 19% of 28,351 genes were differentially expressed (false discovery rate < 0.05) between the exposure groups. Key genes regulating the immune system, such as tumor necrosis factor alpha and interferon gamma, as well as genes related to the NF-kappa-beta complex, were significantly downregulated in the high-arsenic group. Arsenic exposure was associated with genome-wide DNA methylation; the high-arsenic group had 3% points higher genome-wide full methylation (> 80% methylation) than the lower-arsenic group. Differentially methylated regions that were hyper-methylated in the high-arsenic group showed enrichment for immune-related gene ontologies that constitute the basic functions of CD4-positive T cells, such as isotype switching and lymphocyte activation and differentiation. In conclusion, chronic arsenic exposure from drinking water was related to changes in the transcriptome and methylome of CD4-positive T cells, both genome wide and in specific genes, supporting the hypothesis that arsenic causes immunotoxicity by interfering with gene expression and regulation.

  • 338.
    Enroth, Stefan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bosdotter Enroth, Sofia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Strong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs2014Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 5, s. 4684-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ideal biomarkers used for disease diagnosis should display deviating levels in affected individuals only and be robust to factors unrelated to the disease. Here we show the impact of genetic, clinical and lifestyle factors on circulating levels of 92 protein biomarkers for cancer and inflammation, using a population-based cohort of 1,005 individuals. For 75% of the biomarkers, the levels are significantly heritable and genome-wide association studies identifies 16 novel loci and replicate 2 previously known loci with strong effects on one or several of the biomarkers with P-values down to 4.4 × 10−58. Integrative analysis attributes as much as 56.3% of the observed variance to non-disease factors. We propose that information on the biomarker-specific profile of major genetic, clinical and lifestyle factors should be used to establish personalized clinical cutoffs, and that this would increase the sensitivity of using biomarkers for prediction of clinical end points.

  • 339.
    Eriksson, Harald
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Bacterial viruses targeting multi-resistant Klebsiella pneumoniae and Escherichia coli2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The global increase in antibiotic resistance levels in bacteria is a growing concern to our society and highlights the need for alternative strategies to combat bacterial infections. Bacterial viruses (phages) are the natural predators of bacteria and are as diverse as their hosts, but our understanding of them is limited. The current levels of knowledge regarding the role that phage play in the control of bacterial populations are poor, despite the use of phage therapy as a clinical therapy in Eastern Europe.

    The aim of this doctoral thesis is to increase knowledge of the diversity and characteristics of bacterial viruses and to assess their potential as therapeutic agents towards multi-resistant bacteria.

    Paper I is the product of de novo sequencing of newly isolated phages that infect and kill multi-resistant Klebsiella pneumoniae. Based on similarities in gene arrangement, lysis cassette type and conserved RNA polymerase, the creation of a new phage genus within Autographivirinae is proposed.

    Paper II describes the genomic and proteomic analysis of a phage of the rare C3 morphotype, a Podoviridae phage with an elongated head that uses multi-resistant Escherichia coli as its host.

    Paper III describes the study of a pre-made phage cocktail against 125 clinical K. pneumoniae isolates. The phage cocktail inhibited the growth of 99 (79 %) of the bacterial isolates tested. This study also demonstrates the need for common methodologies in the scientific community to determine how to assess phages that infect multiple serotypes to avoid false positive results.

    Paper IV studies the effects of phage predation on bacterial virulence: phages were first allowed to prey on a clinical K. pneumoniae isolate, followed by the isolation of phage-resistant bacteria. The phage resistant bacteria were then assessed for their growth rate, biofilm production in vitro. The virulence of the phage resistant bacteria was then assessed in Galleria mellonella. In the single phage treatments, two out of four phages showed an increased virulence in the in G. mellonella, which was also linked to an increased growth rate of the phage resistant bacteria. In multi-phage treatments however, three out of five phage cocktails decreased the bacterial virulence in G. mellonella compared to an untreated control.

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  • 340.
    Eriksson, Harald
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Maciejewska, Barbara
    Latka, Agnieszka
    Majkowska-Skrobek, Grazyna
    Hellstrand, Marios
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Melefors, Öjar
    Wang, Jin-Town
    Kropinski, Andrew M.
    Drulis-Kawa, Zuzanna
    Nilsson, Anders S.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    A suggested new bacteriophage genus, “Kp34likevirus”, within the Autographivirinae subfamily of Podoviridae2015Inngår i: Viruses, ISSN 1999-4915, E-ISSN 1999-4915, Vol. 7, nr 4, s. 1804-1822Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Klebsiella pneumoniae phages vB_KpnP_SU503 (SU503) and vB_KpnP_SU552A (SU552A) are virulent viruses belonging to theAutographivirinae subfamily of Podoviridae that infect and kill multi-resistant K. pneumoniae isolates. Phages SU503 and SU552A show high pairwise nucleotide identity to Klebsiella phages KP34 (NC_013649), F19 (NC_023567) and NTUH-K2044-K1-1 (NC_025418). Bioinformatic analysis of these phage genomes show high conservation of gene arrangement and gene content, conserved catalytically active residues of their RNA polymerase, a common and specific lysis cassette, and form a joint cluster in phylogenetic analysis of their conserved genes. Also, we have performed biological characterization of the burst size, latent period, host specificity (together with KP34 and NTUH-K2044-K1-1), morphology, and structural genes as well as sensitivity testing to various conditions. Based on the analyses of these phages, the creation of a new phage genus is suggested within the Autographivirinae, called “Kp34likevirus” after their type phage, KP34. This genus should encompass the recently genome sequenced Klebsiella phages KP34, SU503, SU552A, F19 and NTUH-K2044-K1-1.

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  • 341.
    Eriksson, Jesper
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Structure-Function Studies of Bacteriophage P2 Integrase and Cox protein2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Probably no group of organisms has been as important as bacteriophages when it comes to the understanding of fundamental biological processes like transcriptional control, DNA replication, site-specific recombination, e.t.c.

    The work presented in this thesis is a contribution towards the complete understanding of these organisms. Two proteins, integrase, and Cox, which are important for the choice of the life mode of bacteriophage P2, are investigated. P2 is a temperate phage, i.e. it can either insert its DNA into the host chromosome (by site-specific recombination) and wait (lysogeny), or it can produce new progeny with the help of the host protein machinery and thereafter lyse the cell (lytic cycle). The integrase protein is necessary for the integration and excision of the phage genome. The Cox protein is involved as a directional factor in the site-specific recombination, where it stimulates excision and inhibits integration. It has been shown that the Cox protein also is important for the choice of the lytic cycle. The choice of life mode is regulated on a transcriptional level, where two mutually exclusive promoters direct whether the lytic cycle (Pe) or lysogeny (Pc) is chosen. The Cox pro-tein has been shown to repress the Pc promoter and thereby making tran-scription from the Pe promoter possible, leading to the lytic cycle. Further, the Cox protein can function as a transcriptional activator on the parasite phage, P4. P4 has gained the ability to adopt the P2 protein machinery to its own purposes.

    In this work the importance of the native size for biologically active integrase and Cox proteins has been determined. Further, structure-function analyses of the two proteins have been performed with focus on the protein-protein interfaces. In addition it is shown that P2 Cox and the P2 relative Wphi Cox changes the DNA topology upon specific binding. From the obtained results a mechanism for P2 Cox-DNA interaction is discussed.

    The results from this thesis can be used in the development of a gene delivery system based on the P2 site-specific recombination system.

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  • 342.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Hellström, Anders
    Rubin, Carl-Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Wang, Chao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Sayyab, Shumaila
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences.
    Kerje, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    David, Gourichon
    INRA, PEAT, Nouzilly, France.
    Bed'hom, Bertrand
    INRA, AgroParisTech, Animal Genetics and Integrative Biology.
    Tixier-Boichard, Michèle
    INRA, AgroParisTech, Animal Genetics and Integrative Biology.
    Andersson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    A frameshift mutation in COMTD1 specifically dilutes pheomelanin pigmentation in chickenManuskript (preprint) (Annet vitenskapelig)
  • 343.
    Eriksson, Mats
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Moseley, Jeffrey L
    Tottey, Stephen
    Del Campo, Jose A
    Quinn, Jeanette
    Kim, Youngbae
    Merchant, Sabeeha
    Genetic dissection of nutritional copper signaling in chlamydomonas distinguishes regulatory and target genes2004Inngår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 168, nr 2, s. 795-807Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A genetic screen for Chlamydomonas reinhardtii mutants with copper-dependent growth or nonphotosynthetic phenotypes revealed three loci, COPPER RESPONSE REGULATOR 1 (CRR1), COPPER RESPONSE DEFECT 1 (CRD1), and COPPER RESPONSE DEFECT 2 (CRD2), distinguished as regulatory or target genes on the basis of phenotype. CRR1 was shown previously to be required for transcriptional activation of target genes like CYC6, CPX1, and CRD1, encoding, respectively, cytochrome c(6) (which is a heme-containing substitute for copper-containing plastocyanin), coproporphyrinogen III oxidase, and Mg-protoporphyrin IX monomethylester cyclase. We show here that CRR1 is required also for normal accumulation of copper proteins like plastocyanin and ferroxidase in copper-replete medium and for apoplastocyanin degradation in copper-deficient medium, indicating that a single pathway controls nutritional copper homeostasis at multiple levels. CRR1 is linked to the SUPPRESSOR OF PCY1-AC208 13 (SOP13) locus, which corresponds to a gain-of-function mutation resulting in copper-independent expression of CYC6. CRR1 is required also for hypoxic growth, pointing to a physiologically meaningful regulatory connection between copper deficiency and hypoxia. The growth phenotype of crr1 strains results primarily from secondary iron deficiency owing to reduced ferroxidase abundance, suggesting a role for CRR1 in copper distribution to a multicopper ferroxidase involved in iron assimilation. Mutations at the CRD2 locus also result in copper-conditional iron deficiency, which is consistent with a function for CRD2 in a pathway for copper delivery to the ferroxidase. Taken together, the observations argue for a specialized copper-deficiency adaptation for iron uptake in Chlamydomonas.

  • 344.
    Esberg, Anders
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Moqtaderi, Zarmik
    Fan, Xiaochun
    Lu, Jian
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Struhl, Kevin
    Byström, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Iwr1 protein is important for preinitiation complex formation by all three nuclear RNA polymerases in Saccharomyces cerevisiae2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 6, s. e20829-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Iwr1, a protein conserved throughout eukaryotes, was originally identified by its physical interaction with RNA polymerase (Pol) II.

    PRINCIPAL FINDINGS: Here, we identify Iwr1 in a genetic screen designed to uncover proteins involved in Pol III transcription in S. cerevisiae. Iwr1 is important for Pol III transcription, because an iwr1 mutant strain shows reduced association of TBP and Pol III at Pol III promoters, a decreased rate of Pol III transcription, and lower steady-state levels of Pol III transcripts. Interestingly, an iwr1 mutant strain also displays reduced association of TBP to Pol I-transcribed genes and of both TBP and Pol II to Pol II-transcribed promoters. Despite this, rRNA and mRNA levels are virtually unaffected, suggesting a post-transcriptional mechanism compensating for the occupancy defect.

    CONCLUSIONS: Thus, Iwr1 plays an important role in preinitiation complex formation by all three nuclear RNA polymerases.

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  • 345. Fahrer, Jörg
    et al.
    Huelsenbeck, Johannes
    Jaurich, Henriette
    Dörsam, Bastian
    Frisan, Teresa
    Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
    Eich, Marcus
    Roos, Wynand P
    Kaina, Bernd
    Fritz, Gerhard
    Cytolethal distending toxin (CDT) is a radiomimetic agent and induces persistent levels of DNA double-strand breaks in human fibroblasts2014Inngår i: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 18, s. 31-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cytolethal distending toxin (CDT) is a unique genotoxin produced by several pathogenic bacteria. The tripartite protein toxin is internalized into mammalian cells via endocytosis followed by retrograde transport to the ER. Upon translocation into the nucleus, CDT catalyzes the formation of DNA double-strand breaks (DSBs) due to its intrinsic endonuclease activity. In the present study, we compared the DNA damage response (DDR) in human fibroblasts triggered by recombinant CDT to that of ionizing radiation (IR), a well-known DSB inducer. Furthermore, we dissected the pathways involved in the detection and repair of CDT-induced DNA lesions. qRT-PCR array-based mRNA and western blot analyses showed a partial overlap in the DDR pattern elicited by CDT and IR, with strong activation of both the ATM-Chk2 and the ATR-Chk1 axis. In line with its in vitro DNase I-like activity on plasmid DNA, neutral and alkaline Comet assay revealed predominant induction of DSBs in CDT-treated fibroblasts, whereas irradiation of cells generated higher amounts of SSBs and alkali-labile sites. Using confocal microscopy, the dynamics of the DSB surrogate marker γ-H2AX was monitored after pulse treatment with CDT or IR. In contrast to the fast induction and disappearance of γ-H2AX-foci observed in irradiated cells, the number of γ-H2AX-foci induced by CDT were formed with a delay and persisted. 53BP1 foci were also generated following CDT treatment and co-localized with γ-H2AX foci. We further demonstrated that ATM-deficient cells are very sensitive to CDT-induced DNA damage as reflected by increased cell death rates with concomitant cleavage of caspase-3 and PARP-1. Finally, we provided novel evidence that both homologous recombination (HR) and non-homologous end joining (NHEJ) protect against CDT-elicited DSBs. In conclusion, the findings suggest that CDT functions as a radiomimetic agent and, therefore, is an attractive tool for selectively inducing persistent levels of DSBs and unveiling the associated cellular responses.

  • 346. Falahati-Anbaran, Mohsen
    et al.
    Lundemo, Sverre
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik.
    Ansell, Stephen W.
    Stenoien, Hans K.
    Contrasting Patterns of Genetic Structuring in Natural Populations of Arabidopsis lyrata Subsp petraea across Different Regions in Northern Europe2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 9, s. e107479-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Level and partitioning of genetic diversity is expected to vary between contrasting habitats, reflecting differences in strength of ecological and evolutionary processes. Therefore, it is necessary to consider processes acting on different time scales when trying to explain diversity patterns in different parts of species' distributions. To explore how historical and contemporary factors jointly may influence patterns of genetic diversity and population differentiation, we compared genetic composition in the perennial herb Arabidopsis lyrata ssp. petraea from the northernmost parts of its distribution range on Iceland to that previously documented in Scandinavia. Leaf tissue and soil were sampled from ten Icelandic populations of A. lyrata. Seedlings were grown from soil samples, and tissue from above-ground and seed bank individuals were genotyped with 21 microsatellite markers. Seed bank density in Icelandic populations was low but not significantly different from that observed in Norwegian populations. While within-population genetic diversity was relatively high on Iceland (H-E = 0.35), among-population differentiation was low (F-ST = 0.10) compared to Norwegian and Swedish populations. Population differentiation was positively associated with geographical distance in both Iceland and Scandinavia, but the strength of this relationship varied between regions. Although topography and a larger distribution range may explain the higher differentiation between mountainous Norwegian relative to lowland populations in Sweden, these factors cannot explain the lower differentiation in Icelandic compared to Swedish populations. We propose that low genetic differentiation among Icelandic populations is not caused by differences in connectivity, but is rather due to large historical effective population sizes. Thus, rather than contemporary processes, historical factors such as survival of Icelandic lineages in northern refugia during the last glacial period may have contributed to the observed pattern.

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    fulltext
  • 347.
    Fall, Tove
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kuja-Halkola, Ralf
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Dobney, Keith
    Univ Liverpool, Dept Archaeol Class & Egyptol, Liverpool, Merseyside, England.
    Westgarth, Carri
    Univ Liverpool, Inst Infect & Global Hlth, Liverpool, Merseyside, England;Univ Liverpool, Inst Vet Sci, Liverpool, Merseyside, England.
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Evidence of large genetic influences on dog ownership in the Swedish Twin Registry has implications for understanding domestication and health associations2019Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 7554Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Dogs were the first domesticated animal and, according to the archaeological evidence, have had a close relationship with humans for at least 15,000 years. Today, dogs are common pets in our society and have been linked to increased well-being and improved health outcomes in their owners. A dog in the family during childhood is associated with ownership in adult life. The underlying factors behind this association could be related to experiences or to genetic influences. We aimed to investigate the heritability of dog ownership in a large twin sample including all twins in the Swedish Twin Registry born between 1926 and 1996 and alive in 2006. Information about dog ownership was available from 2001 to 2016 from national dog registers. The final data set included 85,542 twins from 50,507 twin pairs with known zygosity, where information on both twins were available in 35,035 pairs. Structural equation modeling was performed to estimate additive genetic effects (the heritability), common/shared environmental, and unique/non-shared environmental effects. We found that additive genetic factors largely contributed to dog ownership, with heritability estimated at 57% for females and 51% for males. An effect of shared environmental factors was only observed in early adulthood. In conclusion, we show a strong genetic contribution to dog ownership in adulthood in a large twin study. We see two main implications of this finding: (1) genetic variation may have contributed to our ability to domesticate dogs and other animals and (2) potential pleiotropic effects of genetic variation affecting dog ownership should be considered in studies examining health impacts of dog ownership.

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    fulltext
  • 348.
    Fallahshahroudi, Amir
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Domestication Effects on the Stress Response in Chickens: Genetics, Physiology, and Behaviour2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Animal domestication, the process where animals become adapted to living in proximity to humans, is associated with the alteration of multiple traits, including decreased fearfulness and stress response. With an estimated population of 50 billion, the domesticated chicken is the most populous avian species in the world. Hundreds of chicken breeds have been developed for meat and egg production, hobby or research purposes. Multidirectional selection and the relaxation of natural selection in captivity have created immense phenotypic diversity amongst domesticates in a relatively short evolutionary time. The extensive phenotypic diversity, existence of the wild ancestor, and feasibility of intercrossing various breeds makes the chicken a suitable model animal for deciphering genetic determinants of complex traits such as stress response. We used chicken domestication as a model to gain insights about the mechanisms that regulate stress response in an avian species. We studied behavioural and physiological stress response in the ancestral Red Junglefowl and one of its domesticated progenies, White Leghorn. An advanced intercross between the aforementioned breeds was later used to map genetic loci underlying modification of stress response. The general pattern of the stress response in chickens was comparable with that reported in mammals, however we identified distinctive differences in the stress modulatory pathways in chickens. We showed that changes in the expression levels of several stress modulatory genes in the brain, the pituitary and the adrenal glands underlie the observed modified stress response in domesticated chickens. Using quantitative trait loci (QTL) mapping, several QTL underlying stress induced corticosterone, aldosterone and baseline dehydroepiandrosterone (DHEA) levels were detected. As a next step, we combined QTL mapping with gene expression (eQTL) mapping and narrowed two QTL down to the putative causal genes, SERPINA10 and PDE1C. Both of these genes were differentially expressed in the adrenal glands of White Leghorn and the Red Junglefowl, had overlapping eQTL with hormonal QTL, and their expression levels in the adrenal glands were correlated with plasma levels of corticosterone and al-dosterone. These two genes thus serve as strong candidates for further functional investigation concerning modification of the stress response during domestication. This dissertation increase the knowledge about genetics and physiology of the stress response in an avian species and its modification during domestication. Our findings expand the basic knowledge about the stress response in chicken, which can potentially be used to improve welfare through appropriate genetic selection.

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    Domestication Effects on the Stress Response in Chickens: Genetics, Physiology, and Behaviour
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  • 349.
    Fallahshahroudi, Amir
    et al.
    Uppsala Univ, Sweden.
    Sorato, Enrico
    Reneco Int Wildlife Consultants, U Arab Emirates.
    Altimiras, Jordi
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Jensen, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    The Domestic BCO2 Allele Buffers Low-Carotenoid Diets in Chickens: Possible Fitness Increase Through Species Hybridization2019Inngår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 212, nr 4, s. 1445-1452Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Domestic animals are adapted to conditions vastly different from those of their wild ancestors, and this is particularly true for their diets. The most numerous of all domestic species, the chicken, originated from the Red Junglefowl (RJF), a native of subtropical forests in Southeast Asia. Surprisingly however, in domestic chicken breeds, a common haplotype of the beta-carotene oxygenase 2 (BCO2) gene, which is involved in carotenoid metabolism, is introgressed from a related species, the Gray Junglefowl, and has been under strong selective pressure during domestication. This suggests that a hybridization event may have conferred a fitness advantage on chickens carrying the derived allele. To investigate the possible biological function of the introgressed BCO2 allele in chicken, we introgressed the ancestral BCO2 allele into domestic White Leghorn chickens. We measured gene expression as well as carotenoid accumulation in skin and eggs of chickens carrying either the ancestral or the derived BCO2 allele. The derived haplotype was associated with down-regulation of BCO2 in skin, muscle, and adipose tissue, but not in liver or duodenum, indicating that carotenoid accumulation occurred in the tissues with reduced gene expression. Most importantly, we found that hens with the derived BCO2 genotype were capable of allocating stored carotenoids to their eggs, suggesting a functional benefit through buffering any shortage in the diet during egg production. Nevertheless, it is of interest that loss of function mutations in BCO2 gene are prevalent in other domesticates including cows, rabbits, and sheep, and, given the importance of carotenoids in development, reproduction, and immunity, it is possible that derived BCO2 alleles may provide a general mechanism in multiple domestic species to deal with higher demand for carotenoids in an environment with carotenoid shortage in the diet.

  • 350.
    Fallahshahroudi, Amir
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Sorato, Enrico
    Reneco Int Wildlife Consultants, Abu Dhabi, U Arab Emirates.
    Altimiras, Jordi
    Linkoping Univ, IFM Biol, AVIAN Behav Genom & Physiol Grp, S-58183 Linkoping, Sweden.
    Jensen, Per
    Linkoping Univ, IFM Biol, AVIAN Behav Genom & Physiol Grp, S-58183 Linkoping, Sweden.
    The Domestic BCO2 Allele Buffers Low-Carotenoid Diets in Chickens: Possible Fitness Increase Through Species Hybridization2019Inngår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 212, nr 4, s. 1445-1452Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Domestic animals are adapted to conditions vastly different from those of their wild ancestors, and this is particularly true for their diets. The most numerous of all domestic species, the chicken, originated from the Red Junglefowl (RJF), a native of subtropical forests in Southeast Asia. Surprisingly however, in domestic chicken breeds, a common haplotype of the beta-carotene oxygenase 2 (BCO2) gene, which is involved in carotenoid metabolism, is introgressed from a related species, the Gray Junglefowl, and has been under strong selective pressure during domestication. This suggests that a hybridization event may have conferred a fitness advantage on chickens carrying the derived allele. To investigate the possible biological function of the introgressed BCO2 allele in chicken, we introgressed the ancestral BCO2 allele into domestic White Leghorn chickens. We measured gene expression as well as carotenoid accumulation in skin and eggs of chickens carrying either the ancestral or the derived BCO2 allele. The derived haplotype was associated with down-regulation of BCO2 in skin, muscle, and adipose tissue, but not in liver or duodenum, indicating that carotenoid accumulation occurred in the tissues with reduced gene expression. Most importantly, we found that hens with the derived BCO2 genotype were capable of allocating stored carotenoids to their eggs, suggesting a functional benefit through buffering any shortage in the diet during egg production. Nevertheless, it is of interest that loss of function mutations in BCO2 gene are prevalent in other domesticates including cows, rabbits, and sheep, and, given the importance of carotenoids in development, reproduction, and immunity, it is possible that derived BCO2 alleles may provide a general mechanism in multiple domestic species to deal with higher demand for carotenoids in an environment with carotenoid shortage in the diet.

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