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  • 201.
    Cornille, Amandine
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Salcedo, A.
    Univ Toronto, Dept Ecol & Evolutionary Biol, 25 Willcocks St, Toronto, ON M6R 1M3, Canada..
    Kryvokhyzha, Dmytro
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Glemin, Sylvain
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Holm, Karl
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Wright, S. I.
    Univ Toronto, Dept Ecol & Evolutionary Biol, 25 Willcocks St, Toronto, ON M6R 1M3, Canada..
    Lascoux, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Genomic signature of successful colonization of Eurasia by the allopolyploid shepherd's purse (Capsella bursa-pastoris)2016In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 25, no 2, p. 616-629Article in journal (Refereed)
    Abstract [en]

    Polyploidization is a dominant feature of flowering plant evolution. However, detailed genomic analyses of the interpopulation diversification of polyploids following genome duplication are still in their infancy, mainly because of methodological limits, both in terms of sequencing and computational analyses. The shepherd's purse (Capsella bursa-pastoris) is one of the most common weed species in the world. It is highly self-fertilizing, and recent genomic data indicate that it is an allopolyploid, resulting from hybridization between the ancestors of the diploid species Capsella grandiflora and Capsella orientalis. Here, we investigated the genomic diversity of C.bursa-pastoris, its population structure and demographic history, following allopolyploidization in Eurasia. To that end, we genotyped 261 C.bursa-pastoris accessions spread across Europe, the Middle East and Asia, using genotyping-by-sequencing, leading to a total of 4274 SNPs after quality control. Bayesian clustering analyses revealed three distinct genetic clusters in Eurasia: one cluster grouping samples from Western Europe and Southeastern Siberia, the second one centred on Eastern Asia and the third one in the Middle East. Approximate Bayesian computation (ABC) supported the hypothesis that C.bursa-pastoris underwent a typical colonization history involving low gene flow among colonizing populations, likely starting from the Middle East towards Europe and followed by successive human-mediated expansions into Eastern Asia. Altogether, these findings bring new insights into the recent multistage colonization history of the allotetraploid C.bursa-pastoris and highlight ABC and genotyping-by-sequencing data as promising but still challenging tools to infer demographic histories of selfing allopolyploids.

  • 202.
    Cortes, Andres J.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Waeber, S.
    Lexer, C.
    Sedlacek, J.
    Wheeler, J. A.
    van Kleunen, M.
    Bossdorf, O.
    Hoch, G.
    Rixen, C.
    Wipf, S.
    Karrenberg, Sophie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Small-scale patterns in snowmelt timing affect gene flow and the distribution of genetic diversity in the alpine dwarf shrub Salix herbacea2014In: Heredity, ISSN 0018-067X, E-ISSN 1365-2540, Vol. 113, no 3, p. 233-239Article in journal (Refereed)
    Abstract [en]

    Current threats to biodiversity, such as climate change, are thought to alter the within-species genetic diversity among microhabitats in highly heterogeneous alpine environments. Assessing the spatial organization and dynamics of genetic diversity within species can help to predict the responses of organisms to environmental change. In this study, we evaluated whether small-scale heterogeneity in snowmelt timing restricts gene flow between microhabitats in the common long-lived dwarf shrub Salix herbacea L. We surveyed 273 genets across 12 early-and late-snowmelt sites (that is, ridges and snowbeds) in the Swiss Alps for phenological variation over 2 years and for genetic variation using seven SSR markers. Phenological differentiation triggered by differences in snowmelt timing did not correlate with genetic differentiation between microhabitats. On the contrary, extensive gene flow appeared to occur between microhabitats and slightly less extensively among adjacent mountains. However, ridges exhibited significantly lower levels of genetic diversity than snowbeds, and patterns of effective population size (Ne) and migration (Nem) between microhabitats were strongly asymmetric, with ridges acting as sources and snowbeds as sinks. As no recent genetic bottlenecks were detected in the studied sites, this asymmetry is likely to reflect current metapopulation dynamics of the species dominated by gene flow via seeds rather than ancient re-colonization after the last glacial period. Overall, our results suggest that seed dispersal prevents snowmelt-driven genetic isolation, and snowbeds act as sinks of genetic diversity. We discuss the consequences of such small-scale variation in gene flow and diversity levels for population responses to climate change.

  • 203.
    Cortobius Fredriksson, Moa
    Södertörn University College, School of Life Sciences.
    ProBenefit: Implementing the Convention on Biological Diversity in the Ecuadorian Amazon2009Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [en]

    Legislation on benefit sharing dates back to 1992 and the commandment of the UNConvention on Biological Diversity, hence implementation still has few cases to fall back on(CBD, 1992). The case study of the project ProBenefit presented by the thesis highlights howlack of deliberation can undermine a democratic process. The objective of the thesis is thatProBenefit’s attempt to implement the standards of the CBD on access and benefit sharingwill highlight not only problems met by this specific project, but difficulties that generallymeet democratic processes in contexts of high inequality. To define if the project ProBenefitsucceeded in carrying out a deliberative process the project will be analyzed by the criteria:access to information, representation, legitimacy and involvement.The population in the project area of ProBenefit had a long history of social marginalization,which made it hard for foreign projects to gain legitimacy. The lack of independentorganizations and the late establishment of the project, which resulted in time shortage, madeit impossible to prevent the distrust of the local population. The failure of the projectcoordinators to ensure active participation of all stakeholders resulted in a late and lowinvolvement of the local participants. The absence of independent organization also madedemocratic legitimacy of the process questionable. Even if ProBenefit had a vision ofdemocratic deliberation the project was unable to break down the prevailing unequal powerdistribution which resulted in an unsustainable process and failure. The conclusion of thethesis is that the attainment of deliberation foremost depends on how a project deals with theexisting distribution of power and how it succeeds in involving all stakeholders.

  • 204. Cossu, Rosa Maria
    et al.
    Casola, Claudio
    Giacomello, Stefania
    Vidalis, Amaryllis
    Scofield, Douglas G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Zuccolo, Andrea
    LTR Retrotransposons Show Low Levels of Unequal Recombination and High Rates of Intraelement Gene Conversion in Large Plant Genomes2017In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 9, no 12, p. 3449-3462Article in journal (Refereed)
  • 205. Cossu, Rosa Maria
    et al.
    Casola, Claudio
    Giacomello, Stefania
    Vidalis, Amaryllis
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Section of Population Epigenetics and Epigenomics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Freising, Germany.
    Scofield, Douglas G.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Ecology and Genetics: Evolutionary Biology, Uppsala University, Sweden; Uppsala Multidisciplinary Center for Advanced Computational Science, Uppsala University, Sweden.
    Zuccolo, Andrea
    LTR Retrotransposons Show Low Levels of Unequal Recombination and High Rates of Intraelement Gene Conversion in Large Plant Genomes2017In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 9, no 12, p. 3449-3462Article in journal (Refereed)
    Abstract [en]

    The accumulat on and removal of transposable elements (TEs) is a major driver of genome size evolution in eukaryotes. In plants, long terminal repeat (LTR) retrotransposons (LTR-RTs) represent the majority of TEs and form most of the nuclear DNA in large genomes. Unequal recombination (UR) between LTRs leads to removal of intervening sequence and formation of solo-LTRs. UR is a major mechanism of LTR-RT removal in many angiosperms, but our understanding of LTR-RT-associated recombination within the large, LTR-RT-rich genomes of conifers is quite limited. We employ a novel read based methodology to estimate the relative rates of LTR-RT-associated UR within the genomes of four conifer and seven angiosperm species. We found the lowest rates of UR in the largest genomes studied, conifers and the angiosperm maize. Recombination may also resolve as gene conversion, which does not remove sequence, so we analyzed LTR-RT-associated gene conversion events (GCEs) in Norway spruce and six angiosperms. Opposite the trend for UR, we found the highest rates of GCEs in Norway spruce and maize. Unlike previous work in angiosperms, we found no evidence that rates of UR correlate with retroelement structural features in the conifers, suggesting that another process is suppressing UR in these species. Recent results from diverse eukaryotes indicate that heterochromatin affects the resolution of recombination, by favoring gene conversion over crossing-over, similar to our observation of opposed rates of UR and GCEs. Control of LTR-RT proliferation via formation of heterochromatin would be a likely step toward large genomes in eukaryotes carrying high LTR-RT content.

  • 206. Costa, H.
    et al.
    Xu, X.
    Overbeek, G.
    Vasaikar, S.
    Pawan K. Patro, C.
    Kostopoulou, O. N.
    Jung, M.
    Shafi, G.
    Ananthaseshan, S.
    Tsipras, G.
    Davoudi, B.
    Mohammad, A. -A
    Lam, H.
    Strååt, Klas
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Institutet, Sweden.
    Wilhelmi, V.
    Shang, M.
    Tegner, J.
    Tong, J. C.
    Wong, K. T.
    Söderberg-Naucler, C.
    Yaiw, K. -C
    Human cytomegalovirus may promote tumour progression by upregulating arginase-22016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 30, p. 47221-47231Article in journal (Refereed)
    Abstract [en]

    Background: Both arginase (ARG2) and human cytomegalovirus (HCMV) have been implicated in tumorigenesis. However, the role of ARG2 in the pathogenesis of glioblastoma (GBM) and the HCMV effects on ARG2 are unknown. We hypothesize that HCMV may contribute to tumorigenesis by increasing ARG2 expression. Results: ARG2 promotes tumorigenesis by increasing cellular proliferation, migration, invasion and vasculogenic mimicry in GBM cells, at least in part due to overexpression of MMP2/9. The nor-NOHA significantly reduced migration and tube formation of ARG2-overexpressing cells. HCMV immediate-early proteins (IE1/2) or its downstream pathways upregulated the expression of ARG2 in U-251 MG cells. Immunostaining of GBM tissue sections confirmed the overexpression of ARG2, consistent with data from subsets of Gene Expression Omnibus. Moreover, higher levels of ARG2 expression tended to be associated with poorer survival in GBM patient by analyzing data from TCGA. Methods: The role of ARG2 in tumorigenesis was examined by proliferation-, migration-, invasion-, wound healing- and tube formation assays using an ARG2- overexpressing cell line and ARG inhibitor, N (omega)-hydroxy-nor-L-arginine (nor-NOHA) and siRNA against ARG2 coupled with functional assays measuring MMP2/9 activity, VEGF levels and nitric oxide synthase activity. Association between HCMV and ARG2 were examined in vitro with 3 different GBM cell lines, and ex vivo with immunostaining on GBM tissue sections. The viral mechanism mediating ARG2 induction was examined by siRNA approach. Correlation between ARG2 expression and patient survival was extrapolated from bioinformatics analysis on data from The Cancer Genome Atlas (TCGA). Conclusions: ARG2 promotes tumorigenesis, and HCMV may contribute to GBM pathogenesis by upregulating ARG2.

  • 207. Cotton, James A.
    et al.
    Berriman, Matthew
    Dalén, Love
    Swedish Museum of Natural History, Department of Bioinformatics and Genetics.
    Barnes, Ian
    Eradication genomics-lessons for parasite control2018In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 361, no 6398, p. 130-131Article in journal (Refereed)
  • 208.
    Crona, Filip
    et al.
    Stockholm University, Wenner-Gren Institute, Developmental Biology, Arrhenius laboratories E3, Stockholm SE-10691, Sweden.
    Dahlberg, Olle
    Stockholm University, Wenner-Gren Institute, Developmental Biology, Arrhenius laboratories E3, Stockholm SE-10691, Sweden.
    Lundberg, Lina E
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Larsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Mannervik, Mattias
    Stockholm University, Wenner-Gren Institute, Developmental Biology, Arrhenius laboratories E3, Stockholm SE-10691, Sweden.
    Gene regulation by the lysine demethylase KDM4A in Drosophila2013In: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 737, no 2, p. 453-463Article in journal (Refereed)
    Abstract [en]

    Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic and can vary depending on cell cycle- or developmental stage. KDM4A demethylates H3K36me3, a modification enriched in the 3' end of active genes. The genomic targets and the role of KDM4 proteins in development remain largely unknown. We therefore generated KDM4A mutant Drosophila, and identified 99 mis-regulated genes in first instar larvae. Around half of these genes were down-regulated and the other half up-regulated in dKDM4A mutants. Although heterochromatin protein 1a (HP1a) can stimulate dKDM4A demethylase activity in vitro, we find that they antagonize each other in control of dKDM4A-regulated genes. Appropriate expression levels for some dKDM4A-regulated genes rely on the demethylase activity of dKDM4A, whereas others do not. Surprisingly, although highly expressed, many demethylase-dependent and independent genes are devoid of H3K36me3 in wild-type as well as in dKDM4A mutant larvae, suggesting that some of the most strongly affected genes in dKDM4A mutant animals are not regulated by H3K36 methylation. By contrast, dKDM4A over-expression results in a global decrease in H3K36me3 levels and male lethality, which might be caused by impaired dosage compensation. Our results show that a modest increase in global H3K36me3 levels is compatible with viability, fertility, and the expression of most genes, whereas decreased H3K36me3 levels are detrimental in males.

  • 209.
    Crooks, Lucy
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Nettelblad, Carl
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Scientific Computing. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computational Science.
    Carlborg, Örjan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    An improved method for estimating chromosomal line origin in QTL analysis of crosses between outbred lines2011In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 1, p. 57-64Article in journal (Refereed)
  • 210.
    Cárdenas, Paco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Moore, Jon A.
    Wilkes Honors College, Florida Atlantic University.
    First records of Geodia demosponges from the New England seamounts, an opportunity to test the use of DNA mini-barcodes on museum specimens2017In: Marine Biodiversity, ISSN 1867-1616, E-ISSN 1867-1624Article in journal (Refereed)
    Abstract [en]

    We report the first records of the sponge genus Geodia (Demospongiae, Tetractinellida, Geodiidae) from the New England Seamounts and Muir Seamount, at lower bathyal depths. Nine specimens collected between 2000 and 2005 belong to two boreal species (Geodia macandrewii and Geodia barretti) and a temperate species (Geodia megastrella). These records extend the distributions of these deep-sea amphi-Atlantic species to the west. Most of these specimens were originally fixed in formalin, which substantially degraded the DNA. We nonetheless managed to sequence two cytochrome c oxidase subunit I (COI) mini-barcodes: the universal mini-barcode at the 5′ end of the Folmer barcode (130 bp) and a newly proposed mini-barcode at the 3′ end of the Folmer barcode (296 bp). These mini-barcodes unambiguously confirmed our identifications. As an additional test, we also successfully sequenced these two mini-barcodes from the holotype of G. barretti, collected in 1855. We conclude by advocating the use of mini-barcodes on formalin-fixed or old specimens with degraded DNA.

  • 211.
    Dahlberg, Helena
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Has modern Swedish forestry affected genetic diversity in Norway spruce stands?2015Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    Norway spruce is one of two dominating species in Swedish forestry and the most economically important tree species in Sweden. In order to preserve the ability to adapt to a changing environment and to keep populations healthy, genetic diversity has to be preserved. When choosing a small number of individuals from a natural stand to establish a seed orchard the population size decrease. With only a small number of genetically different individuals the risk of inbreeding increase. Furthermore if many clones of the same tree are used in one seed orchard there is also an increased risk selfing. The aim of this study was therefore to investigate whether genetic diversity in Norway spruce differs between age groups and if this can be attributed to forestry practices. All sampling was done from a single location in Västerbotten, Sweden and the different age groups were chosen to represent stands not affected by the modern forest industry to recently planted forests. The chosen age groups are young (12-18 years), intermediate (30-45 years), and old (above 85 years). From each age group 150 individuals were sampled. With genomic microsatellite markers each individual was genotyped at eight simple sequence repeat (SSR) loci. Results show an overall high genetic diversity with an average expected heterozygosity (He) at 0.842 and low genetic differentiation with an average fixation index among populations (FST) of 0.003. The genetic diversity of each age group was also high (He 0.832 to 0.843) and the inbreeding coefficient ranged from 0.061 in the old group to 0.078 in the intermediate group. The pairwise FST value was highest between the old group and the young group but the differentiation was only 0.005 (P=0.001). An analysis of molecular variance also showed that only 0.34% of the total genetic variance was explained by differences among age groups. This study found little evidence for a decrease in genetic diversity due to forestry practices and revealed high genetic diversity and low differentiation between the age groups, indicating a healthy population.

  • 212.
    Dahl-Halvarsson, Martin
    et al.
    University of Gothenburg, Gothenburg, Sweden.
    Olive, Montse
    Institut Investigació Biomèdica de Bellvitge – Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.
    Pokrzywa, Malgorzata
    University of Gothenburg, Gothenburg, Sweden.
    Ejeskär, Katarina
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Palmer, Ruth H.
    University of Gothenburg, Gothenburg, Sweden.
    Uv, Anne Elisabeth
    University of Gothenburg, Gothenburg, Sweden.
    Tajsharghi, Homa
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Drosophila model of myosin myopathy rescued by overexpression of a TRIM-protein family member2018In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 28, p. E6566-E6575Article in journal (Refereed)
    Abstract [en]

    Myosin is a molecular motor indispensable for body movement and heart contractility. Apart from pure cardiomyopathy, mutations in MYH7 encoding slow/β-cardiac myosin heavy chain also cause skeletal muscle disease with or without cardiac involvement. Mutations within the α-helical rod domain of MYH7are mainly associated with Laing distal myopathy. To investigate the mechanisms underlying the pathology of the recurrent causative MYH7 mutation (K1729del), we have developed a Drosophila melanogaster model of Laing distal myopathy by genomic engineering of the Drosophila Mhc locus. Homozygous MhcK1728del animals die during larval/pupal stages, and both homozygous and heterozygous larvae display reduced muscle function. Flies expressing only MhcK1728del in indirect flight and jump muscles, and heterozygous MhcK1728del animals, were flightless, with reduced movement and decreased lifespan. Sarcomeres of MhcK1728del mutant indirect flight muscles and larval body wall muscles were disrupted with clearly disorganized muscle filaments. Homozygous MhcK1728del larvae also demonstrated structural and functional impairments in heart muscle, which were not observed in heterozygous animals, indicating a dose-dependent effect of the mutated allele. The impaired jump and flight ability and the myopathy of indirect flight and leg muscles associated with MhcK1728del were fully suppressed by expression of Abba/Thin, an E3-ligase that is essential for maintaining sarcomere integrity. This model of Laing distal myopathy in Drosophila recapitulates certain morphological phenotypic features seen in Laing distal myopathy patients with the recurrent K1729del mutation. Our observations that Abba/Thin modulates these phenotypes suggest that manipulation of Abba/Thin activity levels may be beneficial in Laing distal myopathy.

  • 213.
    Damen, Wim
    et al.
    Universität zu Köln.
    Janssen, Ralf
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Prpic, Nikola-Michael
    Universität zu Köln.
    Pair rule gene orthologs in spider segmentation2005In: Evolution & Development, ISSN 1520-541X, E-ISSN 1525-142X, Vol. 7, no 6, p. 618-628Article in journal (Refereed)
    Abstract [en]

    The activation of pair rule genes is the first indication of the metameric organization of the Drosophila embryo and thus forms a key step in the segmentation process. There are two classes of pair rule genes in Drosophila: the primary pair rule genes that are directly activated by the maternal and gap genes and the secondary pair rule genes that rely on input from the primary pair rule genes. Here we analyze orthologs of Drosophila primary and secondary pair rule orthologs in the spider Cupiennius salei. The expression patterns of the spider pair rule gene orthologs can be subdivided in three groups: even-skipped and runt-1 expression is in stripes that start at the posterior end of the growth zone and their expression ends before the stripes reach the anterior end of the growth zone, while hairy and pairberry-3 stripes also start at the posterior end, but do not cease in the anterior growth zone. Stripes of odd-paired, odd-skipped-related-1, and sloppy paired are only found in the anterior portion of the growth zone. The various genes thus seem to be active during different phases of segment specification. It is notable that the spider orthologs of the Drosophila primary pair rule genes are active more posterior in the growth zone and thus during earlier phases of segment specification than most orthologs of Drosophila secondary pair rule genes, indicating that parts of the hierarchy might be conserved between flies and spiders. The spider ortholog of the Drosophila pair rule gene fushi tarazu is not expressed in the growth zone, but is expressed in a Hox-like fashion. The segmentation function of fushi tarazu thus appears to be a newly acquired role of the gene in the lineage of the mandibulate arthropods.

    PMID:16336415

  • 214.
    Dandage, Rohan
    et al.
    CSIR Inst Genom & Integrat Biol, New Delhi, India;AcSIR, New Delhi, India.
    Pandey, Rajesh
    CSIR Inst Genom & Integrat Biol, CSIR Ayurgen Unit, TRISUTRA, New Delhi, India;MRC Harwell Inst, Mammalian Genet Unit, Harwell Sci & Innovat Campus, Didcot, Oxon, England.
    Jayaraj, Gopal
    CSIR Inst Genom & Integrat Biol, New Delhi, India;AcSIR, New Delhi, India;Max Planck Inst Biochem, Dept Cellular Biochem, Martinsried, Germany.
    Rai, Manish
    CSIR Inst Genom & Integrat Biol, New Delhi, India;AcSIR, New Delhi, India.
    Berger, David
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Chakraborty, Kausik
    CSIR Inst Genom & Integrat Biol, New Delhi, India;AcSIR, New Delhi, India.
    Differential strengths of molecular determinants guide environment specific mutational fates2018In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 14, no 5, article id e1007419Article in journal (Refereed)
    Abstract [en]

    Organisms maintain competitive fitness in the face of environmental challenges through molecular evolution. However, it remains largely unknown how different biophysical factors constrain molecular evolution in a given environment. Here, using deep mutational scanning, we quantified empirical fitness of >2000 single site mutants of the Gentamicin-resistant gene (GmR) in Escherichia coli, in a representative set of physical (non-native temperatures) and chemical (small molecule supplements) environments. From this, we could infer how different biophysical parameters of the mutations constrain molecular function in different environments. We find ligand binding, and protein stability to be the best predictors of mutants' fitness, but their relative predictive power differs across environments. While protein folding emerges as the strongest predictor at minimal antibiotic concentration, ligand binding becomes a stronger predictor of mutant fitness at higher concentration. Remarkably, strengths of environment-specific selection pressures were largely predictable from the degree of mutational perturbation of protein folding and ligand binding. By identifying structural constraints that act as determinants of fitness, our study thus provides coarse mechanistic insights into the environment specific accessibility of mutational fates.

  • 215.
    Daniel, Chammiran
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Silberberg, Gilad
    Behm, Mikaela
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Öhman, Marie
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Alu elements shape the primate transcriptome by cis-regulation of RNA editing2014In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 15, no 2, article id R28Article in journal (Refereed)
    Abstract [en]

    Background: RNA editing by adenosine to inosine deamination is a widespread phenomenon, particularly frequent in the human transcriptome, largely due to the presence of inverted Alu repeats and their ability to form double-stranded structures - a requisite for ADAR editing. While several hundred thousand editing sites have been identified within these primate-specific repeats, the function of Alu-editing has yet to be elucidated. Results: We show that inverted Alu repeats, expressed in the primate brain, can induce site-selective editing in cis on sites located several hundred nucleotides from the Alu elements. Furthermore, a computational analysis, based on available RNA-seq data, finds that site-selective editing occurs significantly closer to edited Alu elements than expected. These targets are poorly edited upon deletion of the editing inducers, as well as in homologous transcripts from organisms lacking Alus. Sequences surrounding sites near edited Alus in UTRs, have been subjected to a lesser extent of evolutionary selection than those far from edited Alus, indicating that their editing generally depends on cis-acting Alus. Interestingly, we find an enrichment of primate-specific editing within encoded sequence or the UTRs of zinc finger-containing transcription factors. Conclusions: We propose a model whereby primate-specific editing is induced by adjacent Alu elements that function as recruitment elements for the ADAR editing enzymes. The enrichment of site-selective editing with potentially functional consequences on the expression of transcription factors indicates that editing contributes more profoundly to the transcriptomic regulation and repertoire in primates than previously thought.

  • 216.
    Darolti, Iulia
    et al.
    UCL, Dept Genet Evolut & Environm, London, England.
    Wright, Alison E.
    UCL, Dept Genet Evolut & Environm, London, England;Univ Sheffield, Dept Anim & Plant Sci, Sheffield, S Yorkshire, England.
    Pucholt, Pascal
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Dept Plant Biol, Uppsala, Sweden.
    Berlin, Sofia
    Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Dept Plant Biol, Uppsala, Sweden.
    Mank, Judith E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology. UCL, Dept Genet Evolut & Environm, London, England.
    Slow evolution of sex-biased genes in the reproductive tissue of the dioecious plant Salix viminalis2018In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 27, no 3, p. 694-708Article in journal (Refereed)
    Abstract [en]

    The relative rate of evolution for sex-biased genes has often been used as a measure of the strength of sex-specific selection. In contrast to studies in a wide variety of animals, far less is known about the molecular evolution of sex-biased genes in plants, particularly in dioecious angiosperms. Here, we investigate the gene expression patterns and evolution of sex-biased genes in the dioecious plant Salix viminalis. We observe lower rates of sequence evolution for male-biased genes expressed in the reproductive tissue compared to unbiased and female-biased genes. These results could be partially explained by the lower codon usage bias for male-biased genes leading to elevated rates of synonymous substitutions compared to unbiased genes. However, the stronger haploid selection in the reproductive tissue of plants, together with pollen competition, would also lead to higher levels of purifying selection acting to remove deleterious variation. Future work should focus on the differential evolution of haploid- and diploid-specific genes to understand the selective dynamics acting on these loci.

  • 217. Das, S
    et al.
    Lagercrantz, Ulf
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Functional Genomics. Evolutionär Funktionsgenomik.
    Lascoux, Martin
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Department of Evolution, Genomics and Systematics, Evolutionary Functional Genomics. Evolutionär Funktionsgenomik.
    Black mustard2006In: Genome mapping and molecular breeding in plants: Oilseeds, Springer, , 2006Chapter in book (Refereed)
  • 218.
    Daskalaki, Evangelia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Archaeological Genetics - Approaching Human History through DNA Analysis2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    There are a variety of archaeological questions, which are difficult to assess by traditional archaeological methods. Similarly, there are genetic and population genetic questions about human evolution and migration that are difficult to assess by studying modern day genetic variation. Archaeological genetics can directly study the archaeological remains, allowing human history to be explored by means of genetics, and genetics to be expanded into historical and pre-historical times. Examples of archaeological questions that can be resolved by genetics are determining biological sex on archaeological remains and exploring the kinship or groups buried in close proximity. Another example is one of the most important events in human prehistory – the transition from a hunter-gatherer lifestyle to farming - was driven through the diffusion of ideas or with migrating farmers. Molecular genetics has the potential to contribute in answering all these questions as well as others of similar nature. However, it is essential that the pitfalls of ancient DNA, namely fragmentation, damage and contamination are handled during data collection and data analysis.

    Analyses of ancient DNA presented in this thesis are based on both mitochondrial DNA and nuclear DNA through the study of single nuclear polymorphisms (SNPs). I used pyrosequencing assays in order to identify the biological sex of archaeological remains as well as verifying if fragmented remains were human or from animal sources. I used a clonal assay approach in order to retrieve sequences for the HVRI of a small family-like burial constellation from the Viking age. By the use of low coverage shotgun sequencing I retrieved sequence data from 13 crew members from the 17th century Swedish man-of-war Kronan. This data was used to determine the ancestry of the crew, which in some cases was speculated to be of non-Scandinavian or non-European origin. However, I demonstrate that all individuals were of European ancestry. Finally, I retrieved sequence data from a Neolithic farmer from the Iberian Peninsula, which added one more facet of information in exploring the Neolithization process of Europe. The Neolithic Iberian individual was genetically similar to Scandinavian Neolithic farmers, indicating that the genetic variation of prehistoric Europe correlated with subsistence mode rather than with geography.

  • 219.
    Daskalaki, Evangelia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Andersson, Lars
    Stockholms läns museum.
    Wilerslev, Eske
    Statens Naturhistoriske Museum.
    Götherström, Anders
    Stockholm University.
    Mitochondrial DNA reveals a lack of kin relations in a suspected Viking age family constellation from a Swedish proto-Christian burial site.Manuscript (preprint) (Other academic)
  • 220.
    Daskalaki, Evangelia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Skoglund, Pontus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Einarson, Lars
    Kalmars läns museum.
    Kjellström, Anna
    Stockholm University.
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Götherström, Anders
    Stockholm University.
    Genomic analysis of biogeographic ancestry of 15 crewmembers from the 300 year-old Swedish man-of-war KronanManuscript (preprint) (Other academic)
  • 221.
    Davoine, Celine
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Abreu, Ilka N.
    Khajeh, Khalil
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Blomberg, Jeanette
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kidd, Brendan N.
    Kazan, Kemal
    Schenk, Peer M.
    Gerber, Lorenz
    Nilsson, Ove
    Moritz, Thomas
    Björklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Functional metabolomics as a tool to analyze Mediator function and structure in plants2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0179640Article in journal (Refereed)
    Abstract [en]

    Mediator is a multiprotein transcriptional co-regulator complex composed of four modules; Head, Middle, Tail, and Kinase. It conveys signals from promoter-bound transcriptional regulators to RNA polymerase II and thus plays an essential role in eukaryotic gene regulation. We describe subunit localization and activities of Mediator in Arabidopsis through metabolome and transcriptome analyses from a set of Mediator mutants. Functional metabolomic analysis based on the metabolite profiles of Mediator mutants using multivariate statistical analysis and heat-map visualization shows that different subunit mutants display distinct metabolite profiles, which cluster according to the reported localization of the corresponding subunits in yeast. Based on these results, we suggest localization of previously unassigned plant Mediator subunits to specific modules. We also describe novel roles for individual subunits in development, and demonstrate changes in gene expression patterns and specific metabolite levels in med18 and med25, which can explain their phenotypes. We find that med18 displays levels of phytoalexins normally found in wild type plants only after exposure to pathogens. Our results indicate that different Mediator subunits are involved in specific signaling pathways that control developmental processes and tolerance to pathogen infections.

  • 222. Dawson, Deborah
    et al.
    Ball, Alexander
    Spurgin, Lewis
    Martin-Galvez, David
    Stewart, Ian RK
    Horsburgh, Gavin
    Potter, Jonathan
    Molina-Morales, Mercedes
    Bicknell, Anthony W J
    Preston, Stephanie A J
    Ekblom, Robert
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Slate, Jon
    Burke, Terry
    High-utility conserved avian microsatellite markers enable parentage and population studies across a wide range of species2013In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 14, no 1, p. 176-Article in journal (Refereed)
    Abstract [en]

    Background: Microsatellites are widely used for many genetic studies. In contrast to single nucleotide polymorphism (SNP) and genotyping-by-sequencing methods, they are readily typed in samples of low DNA quality/concentration (e.g. museum/non-invasive samples), and enable the quick, cheap identification of species, hybrids, clones and ploidy. Microsatellites also have the highest cross-species utility of all types of markers used for genotyping, but, despite this, when isolated from a single species, only a relatively small proportion will be of utility. Marker development of any type requires skill and time. The availability of sufficient "off-the-shelf" markers that are suitable for genotypinga wide range of species would not only save resources but also uniquely enablenew comparisons of diversity among taxa at the same set of loci. No other marker types are capable of enabling this. We therefore developed a set of avianmicrosatellite markers with enhanced cross-species utility. Results: We selected highly-conserved sequences with a high number of repeat units in both of two genetically distant species. Twenty-four primer sets were designed from homologous sequences that possessed at least eight repeat units in both the zebra finch (Taeniopygia guttata) and chicken (Gallus gallus). Each primer sequence was a complete match to zebra finch and, after accounting for degenerate bases, at least 86% similar to chicken. We assessed primer-set utilityby genotyping individuals belonging to eight passerine and four non-passerinespecies. The majority of the new Conserved Avian Microsatellite (CAM) markersamplified in all 12 species tested (on average, 94% in passerines and 95% in non-passerines). This new marker set is of especially high utility in passerines, with amean 68% of loci polymorphic per species, compared with 42% in non-passerinespecies. Conclusions: When combined with previously described conserved loci, this new set of conserved markers will not only reduce the necessity and expense ofmicrosatellite isolation for a wide range of genetic studies, including avianparentage and population analyses, but will also now enable comparisons ofgenetic diversity among different species (and populations) at the same set of loci, with no or reduced bias. Finally, the approach used here can be applied to other taxa in which appropriate genome sequences are available.

  • 223.
    De Bustos, Cecilia
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Genetic and Epigenetic Variation in the Human Genome: Analysis of Phenotypically Normal Individuals and Patients Affected with Brain Tumors2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Genetic and epigenetic variation is a key determinant of human diversity and has an impact on disease predisposition. Single nucleotide polymorphisms (SNPs) and copy number polymorphisms (CNPs) are the main forms of genetic variation. The challenge is to distinguish normal variations from disease-associated changes. Combination of genetic and epigenetic alterations, often together with an environmental component, can cause cancer. In paper I, we investigated possible alterations affecting the transcriptional regulation of PDGFRα in patients affected with central nervous system tumors by characterizing the haplotype combinations in the PDGFRA gene promoter. A specific over-representation of one haplotype (H2δ) in primitive neuroectodermal tumors and ependymomas was observed, suggesting a functional role for the ZNF148/PDGFRα pathway in the tumor pathogenesis. In paper II, 50 glioblastomas were analyzed for DNA copy number variation with a chromosome 22 tiling genomic array. While 20% of tumors displayed monosomy 22, copy number variations affecting a portion of chromosome 22 were found in 14% of cases. This implies the presence of genes involved in glioblastoma development on 22q. Paper III described the analysis of copy number variation of 37 ependymomas using the same array. We detected monosomy in 51.5% of the samples. In addition, we identified two overlapping germline deletions of 2.2 Mb and 320 kb (the latter designated as Ep CNP). In order to investigate whether Ep CNP was a common polymorphism in the normal population or had an association with ependymoma development, we constructed a high-resolution PCR product-based microarray covering this locus (paper IV). For this purpose, we developed a program called Sequence Allocator, which automates the process of array design. This approach allowed assessment of copy number variation within regions of segmental duplications. Our results revealed that gains or deletions were identical in size and encompassed 290 kb. Therefore, papers I-IV suggest that some SNPs and CNPs can be regarded as tumor-associated polymorphisms. Finally, paper V describes variation of DNA methylation among fully differentiated tissues by using an array covering ~9% of the human genome. Major changes in the overall methylation were also found in colorectal cancer cell lines lacking one or two DNA methyltransferases.

  • 224.
    de La Torre, Amanda R
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Birol, Inanc
    Bousquet, Jean
    Ingvarsson, Pär K
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Jansson, Stefan
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Jones, Steven J. M
    Keeling, Christopher I
    MacKay, John
    Nilsson, Ove
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Ritland, Kermit
    Street, Nathaniel
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Yanchuk, Alvin
    Zerbe, Philipp
    Bohlmann, Jörg
    Insights into conifer giga-genomes2014In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 166, no 4, p. 1724-1732Article in journal (Refereed)
    Abstract [en]

    Insights from sequenced genomes of major land plant lineages have advanced research in almost every aspect of plant biology. Until recently, however, assembled genome sequences of gymnosperms have been missing from this picture. Conifers of the pine family (Pinaceae) are a group of gymnosperms that dominate large parts of the world's forests. Despite their ecological and economic importance, conifers seemed long out of reach for complete genome sequencing, due in part to their enormous genome size (20-30 Gb) and the highly repetitive nature of their genomes. Technological advances in genome sequencing and assembly enabled the recent publication of three conifer genomes: white spruce (Picea glauca), Norway spruce (Picea abies), and loblolly pine (Pinus taeda). These genome sequences revealed distinctive features compared with other plant genomes and may represent a window into the past of seed plant genomes. This Update highlights recent advances, remaining challenges, and opportunities in light of the publication of the first conifer and gymnosperm genomes.

  • 225.
    de La Torre, Amanda R.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Plant Sciences, University of California–Davis, Davis, CA.
    Li, Zhen
    Van de Peer, Yves
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Plant Biology, Uppsala Biocenter, Swedish University of Agr icultural Sciences, Uppsala, Sweden.
    Contrasting Rates of Molecular Evolution and Patterns of Selection among Gymnosperms and Flowering Plants2017In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 34, no 6, p. 1363-1377Article in journal (Refereed)
    Abstract [en]

    The majority of variation in rates of molecular evolution among seed plants remains both unexplored and unexplained. Although some attention has been given to flowering plants, reports of molecular evolutionary rates for their sister plant clade (gymnosperms) are scarce, and to our knowledge differences in molecular evolution among seed plant clades have never been tested in a phylogenetic framework. Angiosperms and gymnosperms differ in a number of features, of which contrasting reproductive biology, life spans, and population sizes are the most prominent. The highly conserved morphology of gymnosperms evidenced by similarity of extant species to fossil records and the high levels of macrosynteny at the genomic level have led scientists to believe that gymnosperms are slow-evolving plants, although some studies have offered contradictory results. Here, we used 31,968 nucleotide sites obtained from orthologous genes across a wide taxonomic sampling that includes representatives of most conifers, cycads, ginkgo, and many angiosperms with a sequenced genome. Our results suggest that angiosperms and gymnosperms differ considerably in their rates of molecular evolution per unit time, with gymnosperm rates being, on average, seven times lower than angiosperm species. Longer generation times and larger genome sizes are some of the factors explaining the slow rates of molecular evolution found in gymnosperms. In contrast to their slow rates of molecular evolution, gymnosperms possess higher substitution rate ratios than angiosperm taxa. Finally, our study suggests stronger and more efficient purifying and diversifying selection in gymnosperm than in angiosperm species, probably in relation to larger effective population sizes.

  • 226.
    De La Torre, Amanda R
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Lin, Yao-Cheng
    Van de Peer, Yves
    Ingvarsson, Pär K
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Genome-wide analysis reveals diverged patterns of codon bias, gene expression, and rates of sequence evolution in Picea gene families2015In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 7, no 4, p. 1002-1015Article in journal (Refereed)
    Abstract [en]

    The recent sequencing of several gymnosperm genomes has greatly facilitated studying the evolution of their genes and gene families. In this study, we examine the evidence for expression-mediated selection in the first two fully sequenced representatives of the gymnosperm plant clade (Picea abies and Picea glauca). We use genome-wide estimates of gene expression (> 50,000 expressed genes) to study the relationship between gene expression, codon bias, rates of sequence divergence, protein length, and gene duplication. We found that gene expression is correlated with rates of sequence divergence and codon bias, suggesting that natural selection is acting on Picea protein-coding genes for translational efficiency. Gene expression, rates of sequence divergence, and codon bias are correlated with the size of gene families, with large multicopy gene families having, on average, a lower expression level and breadth, lower codon bias, and higher rates of sequence divergence than single-copy gene families. Tissue-specific patterns of gene expression were more common in large gene families with large gene expression divergence than in single-copy families. Recent family expansions combined with large gene expression variation in paralogs and increased rates of sequence evolution suggest that some Picea gene families are rapidly evolving to cope with biotic and abiotic stress. Our study highlights the importance of gene expression and natural selection in shaping the evolution of protein-coding genes in Picea species, and sets the ground for further studies investigating the evolution of individual gene families in gymnosperms.

  • 227. Decker, Jared E.
    et al.
    McKay, Stephanie D.
    Rolf, Megan M.
    Kim, JaeWoo
    Molina Alcala, Antonio
    Sonstegard, Tad S.
    Hanotte, Olivier
    Götherström, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Seabury, Christopher M.
    Praharani, Lisa
    Babar, Masroor Ellahi
    de Almeida Regitano, Luciana Correia
    Yildiz, Mehmet Ali
    Heaton, Michael P.
    Liu, Wan-Sheng
    Lei, Chu-Zhao
    Reecy, James M.
    Saif-Ur-Rehman, Muhammad
    Schnabel, Robert D.
    Taylor, Jeremy F.
    Worldwide Patterns of Ancestry, Divergence, and Admixture in Domesticated Cattle2014In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 3, p. e1004254-Article in journal (Refereed)
    Abstract [en]

    The domestication and development of cattle has considerably impacted human societies, but the histories of cattle breeds and populations have been poorly understood especially for African, Asian, and American breeds. Using genotypes from 43,043 autosomal single nucleotide polymorphism markers scored in 1,543 animals, we evaluate the population structure of 134 domesticated bovid breeds. Regardless of the analytical method or sample subset, the three major groups of Asian indicine, Eurasian taurine, and African taurine were consistently observed. Patterns of geographic dispersal resulting from co-migration with humans and exportation are recognizable in phylogenetic networks. All analytical methods reveal patterns of hybridization which occurred after divergence. Using 19 breeds, we map the cline of indicine introgression into Africa. We infer that African taurine possess a large portion of wild African auroch ancestry, causing their divergence from Eurasian taurine. We detect exportation patterns in Asia and identify a cline of Eurasian taurine/indicine hybridization in Asia. We also identify the influence of species other than Bos taurus taurus and B. t. indicus in the formation of Asian breeds. We detect the pronounced influence of Shorthorn cattle in the formation of European breeds. Iberian and Italian cattle possess introgression from African taurine. American Criollo cattle originate from Iberia, and not directly from Africa with African ancestry inherited via Iberian ancestors. Indicine introgression into American cattle occurred in the Americas, and not Europe. We argue that cattle migration, movement and trading followed by admixture have been important forces in shaping modern bovine genomic variation.

  • 228.
    Delgado Vega, Angélica María
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Dissecting the Genetic Basis of Systemic Lupus Erythematosus: The Pursuit of Functional Variants2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease that primarily affects women during the childbearing years. SLE is characterized by the production of autoantibodies against nucleic acids and their interacting proteins. The exact molecular mechanisms leading to the breakdown of self-tolerance remain to a large extent unknown, but it is well established that they are influenced by both non-genetic (i.e. environmental and hormonal) and genetic factors. SLE is a complex, polygenic disease. Several susceptibility variants have been identified in SLE. However, the functional role in disease pathogenesis for the majority of them remains largely unknown.

    This thesis includes case-control association studies where the role of the genes TNFSF4 (Paper I), STAT4 (Paper II), CD226 (Paper III), and BLK (Papers IV and V) in the susceptibility of developing SLE was investigated. The primary focus was on the identification of the functional variants underlying the association. For each of these genes, fine mapping was performed using single nucleotide polymorphisms (SNPs), the linkage disequilibrium (LD) was characterized, and the association was narrowed down to specific haplotypes by means of several different statistical genetic strategies. Candidate variants were prioritized for further functional analysis on the basis of their potential effect on the gene function, their association, and/or biological plausibility. In Paper I, the association of TNFSF4 with SLE was validated and attributed to a risk haplotype tagged by SNPs rs1234317-T and rs12039904-T. Paper II provides evidence supporting the presence of at least two independent genetic effects within the STAT4 gene represented by rs3821236-A and rs7574865-A, which correlated with increased levels of gene expression. In Paper III, a functional allele in CD226 (rs727088-C) was identified, which was responsible for decreased levels in both mRNA and protein expression. In Paper IV, two independent genetic effects in the BLK gene were demonstrated. The first one comprised multiple regulatory variants in high LD that were enriched for NFκB and IRF4 binding sites and correlated with low BLK mRNA levels. The second was a low-frequency missense substitution (Ala71Thr) that decreased the BLK protein half-life. In Paper V, a genetic epistatic interaction between BANK1 rs10516487 (GG) and BLK rs2736340 (TT+TC) was demonstrated. Additional molecular analyses established that these molecules interact physically.  

    These studies have contributed to the dissection of the genetic architecture of SLE. They highlight the allelic heterogeneity of the disease and provide functional links to the associated variants, which has significantly aided in the understanding of SLE disease pathogenesis.

  • 229.
    Demczuk, Walter H.B.
    et al.
    National Microbiology Laboratory, Winnipeg, Canada.
    Sidhu, S.
    National Microbiology Laboratory, Winnipeg, Canada.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University Hospital, Örebro, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.
    Whiley, David M.
    Centre for Clinical Research, The University of Queensland, Brisbane, Australia.
    Allen, Vanessa G.
    Public Health Ontario Laboratories, Toronto , Canada.
    Dillon, Jeremiah R.
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Canada.
    Cole, Michelle J.
    Public Health England, London, United Kingdom.
    Seah, Christine
    Public Health Ontario Laboratories, Toronto, Canada.
    Trembizki, Ella
    Centre for Clinical Research, The University of Queensland, Brisbane, Australia.
    Trees, David L.
    Centers for Disease Control and Prevention, Atlanta GA, United States.
    Kersh, Ellen N.
    Centers for Disease Control and Prevention, Atlanta GA, United States.
    Abrams, A. Jeanine
    Centers for Disease Control and Prevention, Atlanta GA, United States.
    de Vries, Henry J.C.
    STI Outpatient Clinic, Department of Infectious Diseases, Public Health Service Amsterdam, Amsterdam, the Netherlands; Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    van Dam, Alje P.
    Public Health Laboratory, Public Health Service Amsterdam, Amsterdam, the Netherlands; Department of Medical Microbiology, OLVG General Hospital, Amsterdam, the Netherlands; .
    Medina, I.
    National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg MB, Canada.
    Bharat, Amrita
    National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg MB, Canada.
    Mulvey, Michael Richard
    National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg MB, Canada.
    Van Domselaar, Gary
    National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg MB, Canada.
    Martin, Irene E.
    National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg MB, Canada.
    Neisseria gonorrhoeae Sequence Typing for Antimicrobial Resistance: a Novel Antimicrobial Resistance Multilocus Typing Scheme for Tracking Global Dissemination of N. gonorrhoeae Strains2017In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 55, no 5, p. 1454-1468Article in journal (Refereed)
    Abstract [en]

    A curated Web-based user-friendly sequence typing tool based on antimicrobial resistance determinants in Neisseria gonorrhoeae was developed and is publicly accessible (https://ngstar.canada.ca). The N. gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) molecular typing scheme uses the DNA sequences of 7 genes (penA, mtrR, porB, ponA, gyrA, parC, and 23S rRNA) associated with resistance to β-lactam antimicrobials, macrolides, or fluoroquinolones. NG-STAR uses the entire penA sequence, combining the historical nomenclature for penA types I to XXXVIII with novel nucleotide sequence designations; the full mtrR sequence and a portion of its promoter region; portions of ponA, porB, gyrA, and parC; and 23S rRNA sequences. NG-STAR grouped 768 isolates into 139 sequence types (STs) (n = 660) consisting of 29 clonal complexes (CCs) having a maximum of a single-locus variation, and 76 NG-STAR STs (n = 109) were identified as unrelated singletons. NG-STAR had a high Simpson's diversity index value of 96.5% (95% confidence interval [CI] = 0.959 to 0.969). The most common STs were NG-STAR ST-90 (n = 100; 13.0%), ST-42 and ST-91 (n = 45; 5.9%), ST-64 (n = 44; 5.72%), and ST-139 (n = 42; 5.5%). Decreased susceptibility to azithromycin was associated with NG-STAR ST-58, ST-61, ST-64, ST-79, ST-91, and ST-139 (n = 156; 92.3%); decreased susceptibility to cephalosporins was associated with NG-STAR ST-90, ST-91, and ST-97 (n = 162; 94.2%); and ciprofloxacin resistance was associated with NG-STAR ST-26, ST-90, ST-91, ST-97, ST-150, and ST-158 (n = 196; 98.0%). All isolates of NG-STAR ST-42, ST-43, ST-63, ST-81, and ST-160 (n = 106) were susceptible to all four antimicrobials. The standardization of nomenclature associated with antimicrobial resistance determinants through an internationally available database will facilitate the monitoring of the global dissemination of antimicrobial-resistant N. gonorrhoeae strains.

  • 230.
    Demenais, Florence
    et al.
    INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France.;Univ Paris Diderot, Univ Sorbonne Paris Cite, Inst Univ Hematol, Paris, France..
    Margaritte-Jeannin, Patricia
    INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France.;Univ Paris Diderot, Univ Sorbonne Paris Cite, Inst Univ Hematol, Paris, France..
    Barnes, Kathleen C.
    Univ Colorado, Colorado Ctr Personalized Med, Div Biomed Informat & Personalized Med, Denver, CO 80202 USA..
    Cookson, William O. C.
    Natl Heart & Lung Inst, Sect Genom Med, London, England..
    Altmueller, Janine
    Univ Cologne, Cologne Ctr Genom, Cologne, Germany.;Univ Cologne, CMMC, Cologne, Germany..
    Ang, Wei
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA, Australia..
    Barr, R. Graham
    Columbia Univ, Dept Med, New York, NY USA.;Columbia Univ, Div Epidemiol, New York, NY USA..
    Beaty, Terri H.
    Johns Hopkins Univ, Div Genet Epidemiol, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA..
    Becker, Allan B.
    Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB, Canada..
    Beilby, John
    Queen Elizabeth II Med Ctr, Dept Diagnost Genom Lab, PathWest Lab Med, Nedlands, WA, Australia..
    Bisgaard, Hans
    Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark..
    Bjornsdottir, Unnur Steina
    Natl Univ Hosp Iceland, Landspitali, Dept Med, Reykjavik, Iceland..
    Bleecker, Eugene
    Wake Forest Univ, Sch Med, Ctr Gen, Winston Salem, NC 27109 USA..
    Bonnelykke, Klaus
    Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark..
    Boomsma, Dorret I.
    Vrjie Univ, Amsterdam Publ Hlth Res Inst, Dept Biol Psychol, Amsterdam, Netherlands..
    Bouzigon, Emmanuelle
    INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France.;Univ Paris Diderot, Univ Sorbonne Paris Cite, Inst Univ Hematol, Paris, France..
    Brightling, Christopher E.
    Univ Leicester, Glenfield Hosp, Inst Lung Hlth, Leicester, Leics, England..
    Brossard, Myriam
    INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France.;Univ Paris Diderot, Univ Sorbonne Paris Cite, Inst Univ Hematol, Paris, France..
    Brusselle, Guy G.
    Ghent Univ Hosp, Dept Resp Med, Ghent, Belgium.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Resp Med, Rotterdam, Netherlands..
    Burchard, Esteban
    Univ Calif San Francisco, Dept Bioengn & Therapeut Sci & Med, San Francisco, CA 94143 USA..
    Burkart, Kristin M.
    Columbia Univ, Coll Phys & Surg, Div Pulm Allergy & Crit Care, New York, NY USA..
    Bush, Andrew
    Imperial Coll London, Natl Heart & Lung Inst, London, England.;Royal Brompton Harefield Natl Hlth Serv NHS Fdn T, London, England..
    Chan-Yeung, Moira
    Univ British Columbia, Dept Med, Vancouver, BC, Canada..
    Chung, Kian Fan
    Imperial Coll London, Natl Heart & Lung Inst, London, England.;Royal Brompton & Harefield Natl Hlth Serv NHS Tru, Biomed Res Unit, London, England..
    Alves, Alexessander Couto
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Curtin, John A.
    Univ Manchester, Div Infect Immun & Resp Med, Sch Biol Sci, Fac Biol Med & Hlth,Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England..
    Custovic, Adnan
    Imperial Coll London, Dept Pediat, London, England..
    Daley, Denise
    Univ British Columbia, Dept Med, Vancouver, BC, Canada.;Univ British Columbia, Ctr Heart & Lung Innovat, Vancouver, BC, Canada..
    de Jongste, Johan C.
    Univ Med Ctr Rotterdam, Erasmus MC, Div Resp Med, Dept Pediat, Rotterdam, Netherlands..
    Del-Rio-Navarro, Blanca E.
    Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico..
    Donohue, Kathleen M.
    Columbia Univ, Dept Med, New York, NY USA.;Columbia Univ, Div Epidemiol, New York, NY USA..
    Duijts, Liesbeth
    Univ Med Ctr Rotterdam, Erasmus MC, Div Resp Med, Dept Pediat, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Div Neonatol, Rotterdam, Netherlands..
    Eng, Celeste
    Univ Calif San Francisco, Dept Med, San Francisco, CA USA..
    Eriksson, Johan G.
    Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Farrall, Martin
    Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Fedorova, Yuliya
    Russian Acad Sci, Inst Biochem & Genet, Ufa Sci Ctr, Ufa, Russia..
    Feenstra, Bjarke
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Ferreira, Manuel A.
    QIMR Berghofer Med Res Inst, Genet & Computat Biol, Brisbane, Qld, Australia..
    Freidin, Maxim B.
    Tomsk NRMC, Res Inst Med Genet, Populat Genet Lab, Tomsk, Russia..
    Gajdos, Zofia
    Childrens Hosp, Div Genet & Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA.;Broad Inst, Cambridge, MA USA..
    Gauderman, Jim
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA..
    Gehring, Ulrike
    Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Utrecht, Netherlands..
    Geller, Frank
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Genuneit, Jon
    Ulm Univ, Inst Epidemiol & Med Biometry, Ulm, Germany..
    Gharib, Sina A.
    Univ Washington, Dept Med, Seattle, WA USA..
    Gilliland, Frank
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA..
    Granell, Raquel
    Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Graves, Penelope E.
    Univ Arizona, Asthma & Airway Dis Res Ctr, Tucson, AZ USA.;Univ Arizona, Inst BIO5, Tucson, AZ USA..
    Gudbjartsson, Daniel F.
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.;Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland..
    Haahtela, Tari
    Univ Helsinki, Skin & Allergy Hosp, Helsinki, Finland..
    Heckbert, Susan R.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Heederik, Dick
    Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Utrecht, Netherlands..
    Heinrich, Joachim
    Univ Hosp Munich, Inst & Outpatient Clin Occupat Social & En, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, Neuherberg, Germany..
    Heliovaara, Markku
    Natl Inst Hlth & Welf THL, Helsinki, Finland..
    Henderson, John
    Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Himes, Blanca E.
    Univ Penn, Dept Biostat Epidemiol & Informat, Philadelphia, PA 19104 USA..
    Hirose, Hiroshi
    Keio Univ, Dept Internal Med, Hlth Ctr, Tokyo, Japan..
    Hirschhorn, Joel N.
    Broad Inst, Cambridge, MA USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Harvard Med Sch, Dept Pediat, Boston, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA..
    Hofman, Albert
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Holt, Patrick
    Univ Western Australia, Cell Biol Telethon Kids Inst, Subiaco, WA, Australia..
    Hottenga, Jouke
    Vrjie Univ, Amsterdam Publ Hlth Res Inst, Dept Biol Psychol, Amsterdam, Netherlands..
    Hudson, Thomas J.
    Ontario Inst Canc Res, Toronto, ON, Canada.;AbbVie Inc, Redwood City, CA USA..
    Hui, Jennie
    Queen Elizabeth II Med Ctr, Dept Diagnost Genom Lab, PathWest Lab Med, Nedlands, WA, Australia.;Busselton Populat Med Res Inst, Perth, WA, Australia.;Univ Western Australia, Sch Populat & Global Hlth, Nedlands, WA, Australia..
    Imboden, Medea
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.;Univ Basel, Basel, Switzerland..
    Ivanov, Vladimir
    Kursk State Med Univ, Dept Biol Med Genet & Ecol, Kursk, Russia..
    Jaddoe, Vincent W. V.
    Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Dept Pediat, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    James, Alan
    Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Busselton Populat Med Res Inst, Nedlands, WA, Australia.;Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Jarvelin, Marjo-Riitta
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London, England.;Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu, Finland.;Univ Oulu, Bioctr Oulu, Oulu, Finland.;Oulu Univ Hosp, Unit Primary Care, Oulu, Finland..
    Jarvis, Deborah
    Imperial Coll London, Natl Heart & Lung Inst, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Jones, Graham
    Western Sydney Univ, Sch Sci & Hlth, Sydney, NSW, Australia..
    Jonsdottir, Ingileif
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Jousilahti, Pekka
    Natl Inst Hlth & Welf THL, Helsinki, Finland..
    Kabesch, Michael
    Univ Childrens Hosp Regensburg KUNO, Dept Pediat Pneumol & Allergy, Regensburg, Germany..
    Kahonen, Mika
    Univ Tampere, Dept Clin Physiol, Tampere, Finland.;Tampere Univ Hosp, Tampere, Finland..
    Kantor, David B.
    Boston Childrens Hosp, Div Crit Care Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA.;Harvard Med Sch, Dept Anaesthesia, Boston, MA USA..
    Karunas, Alexandra S.
    Russian Acad Sci, Inst Biochem & Genet, Ufa Sci Ctr, Ufa, Russia.;Bashkir State Univ, Dept Genet & Fundamental Med, Ufa, Russia..
    Khusnutdinova, Elza
    Russian Acad Sci, Inst Biochem & Genet, Ufa Sci Ctr, Ufa, Russia.;Bashkir State Univ, Dept Genet & Fundamental Med, Ufa, Russia..
    Koppelman, Gerard H.
    Univ Groningen, Beatrix Childrens Hosp, Univ Med Ctr Groningen, Dept Pediat Pulmonol & Pediat Allergol, Groningen, Netherlands.;Groningen Res Inst Asthma & COPD GRIAC, Groningen, Netherlands..
    Kozyrskyj, Anita L.
    Univ Alberta, Dept Pediat, Edmonton, AB, Canada..
    Kreiner, Eskil
    Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark..
    Kubo, Michiaki
    RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan..
    Kumar, Rajesh
    Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.;Northwestern Univ, Dept Pediat, Div Allergy & Clin Immunol, Feinberg Sch Med, Chicago, IL 60611 USA..
    Kumar, Ashish
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.;Univ Basel, Basel, Switzerland.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Kuokkanen, Mikko
    Natl Inst Hlth & Welf THL, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Lahousse, Lies
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Univ Ghent, Fac Pharmaceut Sci, Pharmaceut Care Unit, Ghent, Belgium..
    Laitinen, Tarja
    Univ Turku, Dept Pulm Med, Turku, Finland.;Turku Univ Hosp, Turku, Finland..
    Laprise, Catherine
    Univ Quebec Chicoutimi, Dept Sci Fondament, Chicoutimi, PQ, Canada.;Ctr Sante & Serv Sociaux Saguenay Lac St Jean, Saguenay, PQ, Canada..
    Lathrop, Mark
    McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada..
    Lau, Susanne
    Charite, Pediat Pneumol & Immunol, Berlin, Germany..
    Lee, Young-Ae
    Max Delbruck Centrum MDC Mol Med, Berlin, Germany.;Charite, Pediat Allergol Expt & Clin Res Ctr, Berlin, Germany..
    Lehtimaki, Terho
    Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, Finland..
    Letort, Sebastien
    INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France.;Univ Paris Diderot, Univ Sorbonne Paris Cite, Inst Univ Hematol, Paris, France..
    Levin, Albert M.
    Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA..
    Li, Guo
    Univ Washington, Dept Med, Seattle, WA USA..
    Liang, Liming
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Loehr, Laura R.
    Univ North Carolina Chapel Hill, Div Gen Med, Chapel Hill, NC USA..
    London, Stephanie J.
    NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA..
    Loth, Daan W.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Manichaikul, Ani
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA..
    Marenholz, Ingo
    Max Delbruck Centrum MDC Mol Med, Berlin, Germany.;Charite, Pediat Allergol Expt & Clin Res Ctr, Berlin, Germany..
    Martinez, Fernando J.
    Univ Arizona, Asthma & Airway Dis Res Ctr, Tucson, AZ USA.;Univ Arizona, Inst BIO5, Tucson, AZ USA..
    Matheson, Melanie C.
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia..
    Mathias, Rasika A.
    Johns Hopkins Univ, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD USA..
    Matsumoto, Kenji
    Natl Res Inst Child Hlth & Dev, Dept Allergy & Clin Immunol, Tokyo, Japan..
    Mbarek, Hamdi
    Vrjie Univ, Amsterdam Publ Hlth Res Inst, Dept Biol Psychol, Amsterdam, Netherlands..
    McArdle, Wendy L.
    Univ Bristol, Sch Social & Community Med, Bristol Bioresource Labs, Bristol, Avon, England..
    Melbye, Mads
    Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark.;Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark.;Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA..
    Melen, Erik
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden.;Sachs Childrens Hosp, Stockholm, Sweden..
    Meyers, Deborah
    Wake Forest Univ, Sch Med, Ctr Gen, Winston Salem, NC 27109 USA..
    Michel, Sven
    Univ Childrens Hosp Regensburg KUNO, Dept Pediat Pneumol & Allergy, Regensburg, Germany..
    Mohamdi, Hamida
    INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France.;Univ Paris Diderot, Univ Sorbonne Paris Cite, Inst Univ Hematol, Paris, France..
    Musk, Arthur W.
    Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA, Australia.;Univ Western Australia, Sch Populat Hlth, Perth, WA, Australia.;Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia..
    Myers, Rachel A.
    Duke Univ, Sch Med, Ctr Appl Genom & Precis Med, Durham, NC USA..
    Nieuwenhuis, Maartje A. E.
    Groningen Res Inst Asthma & COPD GRIAC, Groningen, Netherlands.;Univ Groningen, Dept Pulmonol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Noguchi, Emiko
    Univ Tsukuba, Fac Med, Dept Med Genet, Tsukuba, Ibaraki, Japan..
    O'Connor, George T.
    Boston Univ, Sch Med, Dept Med, Pulmonary Ctr, Boston, MA 02118 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA..
    Ogorodova, Ludmila M.
    Siberian State Med Univ, Dept Fac Pediat, Tomsk, Russia..
    Palmer, Cameron D.
    Broad Inst, Cambridge, MA USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA..
    Palotie, Aarno
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Med, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Neurol, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Psychiat, Boston, MA 02114 USA.;Broad Inst, Stanley Ctr Psychiat Res & Program Med & Populat, Cambridge, MA USA..
    Park, Julie E.
    Univ British Columbia, Dept Med, Vancouver, BC, Canada..
    Pennell, Craig E.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA, Australia..
    Pershagen, Goran
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Polonikov, Alexey
    Kursk State Med Univ, Dept Biol Med Genet & Ecol, Kursk, Russia..
    Postma, Dirkje S.
    Groningen Res Inst Asthma & COPD GRIAC, Groningen, Netherlands.;Univ Groningen, Dept Pulmonol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Probst-Hensch, Nicole
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.;Univ Basel, Basel, Switzerland..
    Puzyrev, Valery P.
    Tomsk NRMC, Res Inst Med Genet, Populat Genet Lab, Tomsk, Russia..
    Raby, Benjamin A.
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Raitakari, Olli T.
    Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland.;Turku Univ Hosp, Turku, Finland..
    Ramasamy, Adaikalavan
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Kings Coll London, Dept Med & Mol Genet, London, England..
    Rich, Stephen S.
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA..
    Robertson, Colin F.
    Murdoch Childrens Res Inst, Respiratory Med, Melbourne, Vic, Australia..
    Romieu, Isabelle
    Mory Univ, Hubert Dept Global Hlth, Atlanta, GA USA.;Natl Inst Publ Hlth, Ctr Populat Hlth Res, Cuernavaca, Morelos, Mexico..
    Salam, Muhammad T.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.;Kern Med, Dept Psychiat, Bakersfield, CA USA..
    Salomaa, Veikko
    Natl Inst Hlth & Welf THL, Helsinki, Finland..
    Schlunssen, Vivi
    Aarhus Univ, Sect Environm Occupat & Hlth, Dept Publ Hlth, Aarhus, Denmark..
    Scott, Robert
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England..
    Selivanova, Polina A.
    Siberian State Med Univ, Dept Fac Therapy, Tomsk, Russia..
    Sigsgaard, Torben
    Aarhus Univ, Sect Environm Occupat & Hlth, Dept Publ Hlth, Aarhus, Denmark..
    Simpson, Angela
    Univ Manchester, Div Infect Immun & Resp Med, Sch Biol Sci, Fac Biol Med & Hlth,Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.;Natl Hlth Serv NHS Fdn Trust, Univ Hosp South Manchester, Manchester, Lancs, England..
    Siroux, Valerie
    INSERM, Inst Adv Biosci, Team Environm Epidemiol Appl Reprod & Resp Hlth, U1209, Grenoble, France.;Univ Grenoble Alpes, CNRS, UMR5309, Inst Adv Biosci,Team Environm Epidemiol Appl Repr, Grenoble, France..
    Smith, Lewis J.
    Northwestern Univ, Div Pulm & Crit Care Med, Feinberg Sch Med, Chicago, IL 60611 USA..
    Solodilova, Maria
    Kursk State Med Univ, Dept Biol Med Genet & Ecol, Kursk, Russia..
    Standl, Marie
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, Neuherberg, Germany..
    Stefansson, Kari
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Strachan, David P.
    St Georges Univ London, Populat Hlth Res Inst, London, England..
    Stricker, Bruno H.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Netherlands Healthcare Inspectorate, The Hague, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Takahashi, Atsushi
    RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan..
    Thompson, Philip J.
    Univ Western Australia, Inst Resp Hlth, Nedlands, WA, Australia.;Univ Western Australia, Harry Perkins Inst Med Res, Nedlands, WA, Australia.;Lung Hlth Clin, Nedlands, WA, Australia..
    Thorleifsson, Gudmar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland..
    Thorsteinsdottir, Unnur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Tiesler, Carla M. T.
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Div Metab Dis & Nutrit Med, Munich, Germany..
    Torgerson, Dara G.
    Univ Calif San Francisco, Dept Med, San Francisco, CA USA..
    Tsunoda, Tatsuhiko
    RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.;Tokyo Med & Dent Univ, Dept Med Sci Math, Med Res Inst, Tokyo, Japan..
    Uitterlinden, Andre G.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    van der Valk, Ralf J. P.
    Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Dept Pediat,Div Resp Med, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Vaysse, Amaury
    INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France.;Univ Paris Diderot, Univ Sorbonne Paris Cite, Inst Univ Hematol, Paris, France..
    Vedantam, Sailaja
    Childrens Hosp, Div Genet & Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA.;Broad Inst, Cambridge, MA USA..
    von Berg, Andrea
    Marien Hosp Wesel, Dept Pediat, Wesel, Germany..
    von Mutius, Erika
    Ludwig Maximilians Univ Munchen, Dr Von Hauner Childrens Hosp, Munich, Germany.;German Ctr Lung Res, Munich, Germany..
    Vonk, Judith M.
    Groningen Res Inst Asthma & COPD GRIAC, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Waage, Johannes
    Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark..
    Wareham, Nick J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England..
    Weiss, Scott T.
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    White, Wendy B.
    Tougaloo Coll, UTEC, Jackson Heart Study, Jackson, MI USA..
    Wickman, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Widen, Elisabeth
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Willemsen, Gonneke
    Vrjie Univ, Amsterdam Publ Hlth Res Inst, Dept Biol Psychol, Amsterdam, Netherlands..
    Williams, L. Keoki
    Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA.;Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI USA..
    Wouters, Inge M.
    Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Utrecht, Netherlands..
    Yang, James J.
    Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England..
    Moffatt, Miriam F.
    Natl Heart & Lung Inst, Sect Genom Med, London, England..
    Ober, Carole
    Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA..
    Nicolae, Dan L.
    Univ Chicago, Dept Stat, Med Genet Sect, Chicago, IL 60637 USA.;Univ Chicago, Dept Human Genet, Med Genet Sect, Chicago, IL 60637 USA.;Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA..
    Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 1, p. 42-+Article in journal (Refereed)
    Abstract [en]

    We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

  • 231.
    den Tex, Robert-Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Patterns and Processes of Evolution in Sundaland2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Biodiversity in the tropics is disproportionately high compared to other habitats, and also under disproportionate threat from human impact. It is necessary to understand how this diversity evolved and how it is partitioned across space in order to preserve it. In this thesis I construct phylogenies of tropical forest dependent vertebrates from Southeast Asia and the islands of the Sunda shelf, a region referred to as Sundaland. I focus on the tree squirrels (genus Sundasciurus) and Asian barbets (Aves: Family Megalaimidae), two taxa with similar ecological characteristics. I use these phylogenies to test hypotheses that have been put forward to explain high levels of tropical diversity including the Pleistocene pump and museum hypotheses. I also use phylogenies to elucidate phylogeographic patterns within the region. I find no evidence for an increase in speciation in the Pleistocene, but I do find within species structure that dates to this period. Common phylogeographic patterns were identified between many forest dependent vertebrates that suggest that populations on the island of Sumatra are generally more closely related to Malay Peninsula populations than to populations on Borneo.

    From a methodological viewpoint we propose careful usage of universal primers in ancient DNA studies because of our finding of increased risk of amplifying pseudogenes of the mtDNA.

  • 232. Dessimoz, Christophe
    et al.
    Gabaldón, Toni
    Roos, David S
    Sonnhammer, Erik L L
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Herrero, Javier
    Toward community standards in the quest for orthologs.2012In: Bioinformatics (Oxford, England), ISSN 1367-4811, Vol. 28, no 6, p. 900-4Article in journal (Refereed)
    Abstract [en]

    The identification of orthologs-genes pairs descended from a common ancestor through speciation, rather than duplication-has emerged as an essential component of many bioinformatics applications, ranging from the annotation of new genomes to experimental target prioritization. Yet, the development and application of orthology inference methods is hampered by the lack of consensus on source proteomes, file formats and benchmarks. The second 'Quest for Orthologs' meeting brought together stakeholders from various communities to address these challenges. We report on achievements and outcomes of this meeting, focusing on topics of particular relevance to the research community at large. The Quest for Orthologs consortium is an open community that welcomes contributions from all researchers interested in orthology research and applications.

  • 233. Didinger, Chelsea
    et al.
    Eimes, John
    Lillie, Mette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Waldman, Bruce
    Multiple major histocompatibility complex class I genes in Asian anurans: Ontogeny and phylogeny2017In: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 70, p. 69-79Article in journal (Refereed)
    Abstract [en]

    Amphibians, as the first terrestrial vertebrates, offer a window into early major histocompatibility complex (MHC) evolution. We characterized the MHC class I of two Korean amphibians, the Asiatic toad (Bufo gargarizans) and the Japanese tree frog (Hyla japonica). We found at least four transcribed MHC class I (MHC I) loci, the highest number confirmed in any anuran to date. Furthermore, we identified MHC I transcripts in terrestrial adults, and possibly in aquatic larvae, of both species. We conducted a phylogenetic analysis based on MHC I sequence data and found that B. gargarizans and H. japonica cluster together in the superfamily Nobleobatrachia. We further identified three supertypes shared by the two species. Our results reveal substantial variation in the number of MHC I loci in anurans and suggest that certain supertypes have particular physiochemical properties that may confer pathogen resistance.

  • 234. Diez-del-Molino, David
    et al.
    Sanchez-Barreiro, Fatima
    Barnes, Ian
    Gilbert, M. Thomas P.
    Dalen, Love
    Quantifying Temporal Genomic Erosion in Endangered Species2018In: Trends in Ecology & Evolution, ISSN 0169-5347, E-ISSN 1872-8383, Vol. 33, no 3, p. 176-185Article in journal (Refereed)
  • 235.
    Dinca, Vlad
    et al.
    Univ Guelph, Biodivers Inst Ontario, Guelph, ON N1G 2W1, Canada..
    Backstrom, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Dapporto, Leonardo
    Oxford Brookes Univ, Dept Biol & Med Sci, Oxford OX3 0BP, England..
    Friberg, Magne
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Garcia-Barros, Enrique
    Univ Autonoma Madrid, Dept Biol, Madrid 28049, Spain..
    Hebert, Paul D. N.
    Univ Guelph, Biodivers Inst Ontario, Guelph, ON N1G 2W1, Canada..
    Hernandez-Roldan, Juan
    Univ Autonoma Madrid, Dept Biol, Madrid 28049, Spain..
    Hornett, Emily
    Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England..
    Lukhtanov, Vladimir
    Russian Acad Sci, Inst Zool, Dept Karyosystemat, St Petersburg 199034, Russia..
    Marec, Frantisek
    Univ South Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic..
    DNA barcodes highlight unique research models in European butterflies2015In: Genome, ISSN 0831-2796, E-ISSN 1480-3321, Vol. 58, no 5, p. 212-212Article in journal (Other academic)
  • 236.
    Dinca, Vlad
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Wiklund, Christer
    Stockholm University, Faculty of Science, Department of Zoology.
    Lukhtanov, V. A.
    Kodandaramaiah, U.
    Norén, Karin
    Stockholm University, Faculty of Science, Department of Zoology.
    Dapporto, L.
    Wahlberg, N.
    Vila, R.
    Friberg, Mange
    Stockholm University, Faculty of Science, Department of Zoology.
    Reproductive isolation and patterns of genetic differentiation in a cryptic butterfly species complex2013In: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 26, no 10, p. 2095-2106Article in journal (Refereed)
    Abstract [en]

    Molecular studies of natural populations are often designed to detect and categorize hidden layers of cryptic diversity, and an emerging pattern suggests that cryptic species are more common and more widely distributed than previously thought. However, these studies are often decoupled from ecological and behavioural studies of species divergence. Thus, the mechanisms by which the cryptic diversity is distributed and maintained across large spatial scales are often unknown. In 1988, it was discovered that the common Eurasian Wood White butterfly consisted of two species (Leptidea sinapis and Leptidea reali), and the pair became an emerging model for the study of speciation and chromosomal evolution. In 2011, the existence of a third cryptic species (Leptidea juvernica) was proposed. This unexpected discovery raises questions about the mechanisms preventing gene flow and about the potential existence of additional species hidden in the complex. Here, we compare patterns of genetic divergence across western Eurasia in an extensive data set of mitochondrial and nuclear DNA sequences with behavioural data on inter- and intraspecific reproductive isolation in courtship experiments. We show that three species exist in accordance with both the phylogenetic and biological species concepts and that additional hidden diversity is unlikely to occur in Europe. The Leptidea species are now the best studied cryptic complex of butterflies in Europe and a promising model system for understanding the formation of cryptic species and the roles of local processes, colonization patterns and heterospecific interactions for ecological and evolutionary divergence.

  • 237.
    Dirks-Mulder, Anita
    et al.
    Naturalis Biodivers Ctr, Endless Forms Grp, Vondellaan 55, NL-2332 AA Leiden, Netherlands.;Univ Appl Sci Leiden, Fac Sci & Technol, Zernikedreef 11, NL-2333 CK Leiden, Netherlands..
    Butot, Roland
    Naturalis Biodivers Ctr, Endless Forms Grp, Vondellaan 55, NL-2332 AA Leiden, Netherlands..
    van Schaik, Peter
    Univ Appl Sci Leiden, Fac Sci & Technol, Zernikedreef 11, NL-2333 CK Leiden, Netherlands..
    Wijnands, Jan Willem P. M.
    Univ Appl Sci Leiden, Fac Sci & Technol, Zernikedreef 11, NL-2333 CK Leiden, Netherlands..
    van den Berg, Roel
    Univ Appl Sci Leiden, Fac Sci & Technol, Zernikedreef 11, NL-2333 CK Leiden, Netherlands..
    Krol, Louie
    Univ Appl Sci Leiden, Fac Sci & Technol, Zernikedreef 11, NL-2333 CK Leiden, Netherlands..
    Doebar, Sadhana
    Univ Appl Sci Leiden, Fac Sci & Technol, Zernikedreef 11, NL-2333 CK Leiden, Netherlands..
    van Kooperen, Kelly
    Univ Appl Sci Leiden, Fac Sci & Technol, Zernikedreef 11, NL-2333 CK Leiden, Netherlands..
    de Boer, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology. Naturalis Biodivers Ctr, Endless Forms Grp, Vondellaan 55, NL-2332 AA Leiden, Netherlands.;Univ Oslo, Nat Hist Museum, POB 1172 Blindern, N-0318 Oslo, Norway..
    Kramer, Elena M.
    Harvard Univ, Dept Organism & Evolutionary Biol, 16 Div Ave, Cambridge, MA 02138 USA..
    Smets, Erik F.
    Naturalis Biodivers Ctr, Endless Forms Grp, Vondellaan 55, NL-2332 AA Leiden, Netherlands.;Katholieke Univ Leuven, Ecol Evolut & Biodivers Conservat cluster, Kasteelpark Arenberg 31, B-3001 Leuven, Belgium..
    Vos, Rutger A.
    Naturalis Biodivers Ctr, Endless Forms Grp, Vondellaan 55, NL-2332 AA Leiden, Netherlands.;Univ Amsterdam, Inst Biodivers & Ecosyst Dynam, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands..
    Vrijdaghs, Alexander
    Katholieke Univ Leuven, Ecol Evolut & Biodivers Conservat cluster, Kasteelpark Arenberg 31, B-3001 Leuven, Belgium..
    Gravendeel, Barbara
    Naturalis Biodivers Ctr, Endless Forms Grp, Vondellaan 55, NL-2332 AA Leiden, Netherlands.;Univ Appl Sci Leiden, Fac Sci & Technol, Zernikedreef 11, NL-2333 CK Leiden, Netherlands.;Leiden Univ, Inst Biol, Sylviusweg 72, NL-2333 BF Leiden, Netherlands..
    Exploring the evolutionary origin of floral organs of Erycina pusilla, an emerging orchid model system2017In: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 17, article id 89Article in journal (Refereed)
    Abstract [en]

    Background: Thousands of flowering plant species attract pollinators without offering rewards, but the evolution of this deceit is poorly understood. Rewardless flowers of the orchid Erycina pusilla have an enlarged median sepal and incised median petal ('lip') to attract oil-collecting bees. These bees also forage on similar looking but rewarding Malpighiaceae flowers that have five unequally sized petals and gland-carrying sepals. The lip of E. pusilla has a 'callus' that, together with winged 'stelidia', mimics these glands. Different hypotheses exist about the evolutionary origin of the median sepal, callus and stelidia of orchid flowers. Results: The evolutionary origin of these organs was investigated using a combination of morphological, molecular and phylogenetic techniques to a developmental series of floral buds of E. pusilla. The vascular bundle of the median sepal indicates it is a first whorl organ but its convex epidermal cells reflect convergence of petaloid features. Expression of AGL6 EpMADS4 and APETALA3 EpMADS14 is low in the median sepal, possibly correlating with its petaloid appearance. A vascular bundle indicating second whorl derivation leads to the lip. AGL6 EpMADS5 and APETALA3 EpMADS13 are most highly expressed in lip and callus, consistent with current models for lip identity. Six vascular bundles, indicating a stamen-derived origin, lead to the callus, stelidia and stamen. AGAMOUS is not expressed in the callus, consistent with its sterilization. Out of three copies of AGAMOUS and four copies of SEPALLATA, EpMADS22 and EpMADS6 are most highly expressed in the stamen. Another copy of AGAMOUS, EpMADS20, and the single copy of SEEDSTICK, EpMADS23, are most highly expressed in the stelidia, suggesting EpMADS22 may be required for fertile stamens. Conclusions: The median sepal, callus and stelidia of E. pusilla appear to be derived from a sepal, a stamen that gained petal identity, and stamens, respectively. Duplications, diversifying selection and changes in spatial expression of different MADS-box genes shaped these organs, enabling the rewardless flowers of E. pusilla to mimic an unrelated rewarding flower for pollinator attraction. These genetic changes are not incorporated in current models and urge for a rethinking of the evolution of deceptive flowers.

  • 238. Dixon, Christopher J
    et al.
    Schoenswetter, Peter
    Suda, Jan
    Wiedermann, Magdalena M
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Schneeweiss, Gerald M
    Reciprocal Pleistocene origin and postglacial range formation of an allopolyploid and its sympatric ancestors (Androsace adfinis group, Primulaceae)2009In: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 50, no 1, p. 74-83Article in journal (Refereed)
    Abstract [en]

    The biogeographic history of polyploids and their lower-ploid ancestors is an important feature to achieve a better understanding of polyploid evolution. This is exemplified here using the ecologically congruent members of the Androsace adfinis group (Primulaceae) endemic to the southwestern European Alps. Employing relative genome size, AFLP fingerprint and chloroplast sequence haplotype data, we show that Androsace brigantiaca is a recent (probably no more than 0.2 million years) allopolyploid derivative of the geographically close A adfinis and A puberula, which formed reciprocally in a comparatively restricted area in the southern Southwestern Alps. Bayesian admixture analysis-also of artificial additive AFLP profiles-shows that the nuclear genome of A. brigantiaca is significantly biased towards the puberula-genome irrespective of maternal parentage. Nevertheless, there is no evidence for genetic interaction (hybridization, introgression) of A brigantiaca with either of its ancestors, including the widely sympatric A. puberula. Sympatry might be facilitated by ecological displacement on a local scale or might be a transitory phase on the way to competitive replacement via, for instance, polyploid superiority.

  • 239.
    Dnyansagar, Rohit
    University of Skövde, School of Life Sciences.
    Investigation of phylogenetic relationships using microRNA sequences and secondary structures2010Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    MicroRNAs are important biomolecules for regulating biological processes. Moreover, the secondary structure of microRNA is important for its activity and has been used previously as a mean for finding unknown microRNAs. A phylogenetic study of the microRNA secondary structure reveals more information than its primary sequence, because the primary sequence can undergo mutations that give rise to different phylogenetic relationships, whereas the secondary structure is more robust against mutations and therefore sometimes  more informative.

    Here we constructed a phylogenetic tree entirely based on microRNA secondary structures using tools PHYLIP (Felsenstein, 1995) and RNAforester (Matthias Höchsmann, 2003, Hochsmann et al., 2004), and compared the overall topology and clusters with the phylogenetic tree constructed using microRNA sequence. The purpose behind this comparison was to investigate the sequence and structure similarity in phylogenetic context and also to investigate if functionally similar microRNA genes are closer in their structure-derived phylogenetic tree.

    Our phylogenetic comparison shows that the sequence similarity has hardly any effect on the structure similarity in the phylogenetic tree. MicroRNAs that have similar function are closer in the phylogenetic tree based on secondary structure than its respective sequence phylogeny. Hence, this approach can be very useful in predicting the functions of the new microRNAs whose function is yet to be known, since the function of the miRNAs heavily relies on its secondary structure.

     

  • 240. Doan, Karolina
    et al.
    Mackiewicz, Pawel
    Sandoval-Castellanos, Edson
    Stefaniak, Krzysztof
    Ridush, Bogdan
    Dalén, Love
    Swedish Museum of Natural History, Department of Bioinformatics and Genetics.
    Weglenski, Piotr
    Stankovic, Ana
    The history of Crimean red deer population and Cervus phylogeography in Eurasia2018In: Zoological Journal of the Linnean Society, ISSN 0024-4082, E-ISSN 1096-3642, Vol. 183, no 1, p. 208-225Article in journal (Refereed)
  • 241. Dobbins, Sara E.
    et al.
    Broderick, Peter
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Feychting, Maria
    Johansen, Christoffer
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Schramm, Johannes
    Olver, Bianca
    Lloyd, Amy
    Ma, Yussanne P.
    Hosking, Fay J.
    Lönn, Stefan
    Ahlbom, Anders
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schoemaker, Minouk J.
    Hepworth, Sarah J.
    Hoffmann, Per
    Muehleisen, Thomas W.
    Noethen, Markus M.
    Moebus, Susanne
    Eisele, Lewin
    Kosteljanetz, Michael
    Muir, Kenneth
    Swerdlow, Anthony
    Simon, Matthias
    Houlston, Richard S.
    Common variation at 10p12.31 near MLLT10 influences meningioma risk2011In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 43, no 9, p. 825-827Article in journal (Refereed)
    Abstract [en]

    To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.

  • 242.
    Domingo Prim, Judit
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    The exosome and the maintenance of genome integrity2016Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The RNA exosome acts on different RNA substrates and plays important roles in RNA metabolism. The fact that short non-coding RNAs are involved in the DNA damage response led us to investigate whether the exosome plays a role in DNA repair. We have shown that the exosome catalytic subunit RRP6/EXOSC10 is recruited to DNA double-strand breaks (DSBs) in Drosophila S2 cells and human HeLa cells exposed to either ionizing radiation or I-PpoI endonuclease cleavage. DIS3, the other catalytic subunit of the nuclear exosome, is also recruited to DSBs, whereas the exosome core subunit EXOSC7 is not. Depletion of different exosome subunits does not interfere with the phosphorylation of the histone variants H2Av (Drosophila) or H2AX (humans), but depletion of RRP6/EXOSC10 impairs the recruitment of the homologous recombination factor RAD51 to the damaged sites, without affecting RAD51 levels. The recruitment of RAD51 to DSBs in S2 cells is also inhibited by overexpression of RRP6-Y361A–V5, a catalytically inactive RRP6 mutant. Furthermore, cells depleted of RRP6 or EXOSC10 are more sensitive to radiation, which is consistent with RRP6/EXOSC10 playing a role in DNA repair. RRP6/EXOSC10 can be co-immunoprecipitated with RAD51, which links RRP6/EXOSC10 to the homologous recombination pathway in animal cells. Taken together, our results suggest that a 3’-5’ ribonucleolytic activity is required for efficient DNA repair. 

  • 243.
    Dondorp, Wybo
    et al.
    Maastricht Univ, Res Sch CAPHRI, Dept Hlth Eth & Soc, NL-6200 MD Maastricht, Netherlands.;Maastricht Univ, Res Sch GROW, Dept Hlth Eth & Soc, NL-6200 MD Maastricht, Netherlands..
    de Wert, Guido
    Maastricht Univ, Res Sch CAPHRI, Dept Hlth Eth & Soc, NL-6200 MD Maastricht, Netherlands.;Maastricht Univ, Res Sch GROW, Dept Hlth Eth & Soc, NL-6200 MD Maastricht, Netherlands..
    Bombard, Yvonne
    Univ Toronto, Fac Med, Li Ka Shing Knowledge Inst, St Michaels Hosp, Toronto, ON, Canada.;Univ Toronto, Fac Med, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada..
    Bianchi, Diana W.
    Tufts Univ, Sch Med, Dept Pediat Obstet & Gynecol, Boston, MA 02111 USA..
    Bergmann, Carsten
    Ctr Human Genet Biosci, Ingelheim, Germany.;Univ Freiburg, Med Ctr, Dept Med, D-79106 Freiburg, Germany..
    Borry, Pascal
    Leuven Univ, Ctr Biomed Eth & Law, Dept Publ Hlth & Primary Care, Louvain, Belgium..
    Chitty, Lyn S.
    Great Ormond St Hosp & UCLH NHS Fdn Trusts, UCL Inst Child Hlth, Clin & Mol Genet Unit, London, England..
    Fellmann, Florence
    Univ Lausanne Hosp, Serv Med Genet, Lausanne, Switzerland..
    Forzano, Francesca
    Osped Galliera, Med Genet Unit, Genoa, Italy..
    Hall, Alison
    PHG Fdn, Cambridge, England..
    Henneman, Lidewij
    Vrije Univ Amsterdam Med Ctr, Sect Community Genet, Dept Clin Genet, Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Howard, Heidi C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Lucassen, Anneke
    Univ Southampton, Dept Clin Eth & Law CELS, Southampton, Hants, England.;Wessex Clin Genet Serv, Southampton, Hants, England..
    Ormond, Kelly
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA USA.;Stanford Univ, Sch Med, Stanford Ctr Biomed Eth, Stanford, CA USA..
    Peterlin, Borut
    Univ Ljubljana, Med Ctr, Clin Inst Med Genet, Ljubljana 61000, Slovenia..
    Radojkovic, Dragica
    Univ Belgrade, IMGGE, Lab Mol Biol, Belgrade, Serbia..
    Rogowski, Wolf
    Helmholtz Zentrum, Deutsch Forschungszentrum Gesundheit & Umwelt, Munich, Germany..
    Soller, Maria
    Lund Univ, Div Clin Genet, Lund, Sweden.;Univ Lund Hosp, Reg Labs Reg Skane, S-22185 Lund, Sweden..
    Tibben, Aad
    Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands..
    Tranebjaerg, Lisbeth
    Bispebjerg Hosp, Rigshosp, Dept Audiol, Copenhagen, Denmark.;Univ Copenhagen, Kennedy Ctr, Dept Clin Genet, Copenhagen, Denmark.;Univ Copenhagen, ICMM, Inst Cellular & Mol Med, Copenhagen, Denmark..
    van El, Carla G.
    Vrije Univ Amsterdam Med Ctr, Sect Community Genet, Dept Clin Genet, Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Cornel, Martina C.
    Vrije Univ Amsterdam Med Ctr, Sect Community Genet, Dept Clin Genet, Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening2015In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 23, no 11, p. 1438-1450Article in journal (Refereed)
    Abstract [en]

    This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non-laboratory aspects such as information and counseling), education of professionals, systematic evaluation of all aspects of prenatal screening, development of better evaluation tools in the light of the aim of the practice, accountability to all stakeholders including children born from screened pregnancies and persons living with the conditions targeted in prenatal screening and promotion of equity of access.

  • 244. Dongre, Mitesh
    et al.
    Khatri, Neelam
    Dureja, Chetna
    Raychaudhuri, Saumya
    Alanine-scanning mutagenesis of selected residues in the N-terminal region alters the functionality of LuxO: lessons from a natural variant LuxOPL91.2011In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 60, no Pt 6, p. 856-60Article in journal (Refereed)
  • 245. Dongre, Mitesh
    et al.
    Tripathi, Ranjana
    Jain, Vibhu
    Raychaudhuri, Saumya
    Functional independence of a variant LuxOPL91 from a non-O1 non-O139 Vibrio cholerae over the activity of CsrA and Fis.2008In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 57, no Pt 8, p. 1041-5Article in journal (Refereed)
  • 246.
    D'Onofrio, Brian M.
    et al.
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA.
    Class, Quetzal A.
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA.
    Rickert, Martin E.
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA.
    Sujan, Ayesha C.
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA.
    Larsson, Henrik
    Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Karolinska Institutet, Stockholm, Sweden.
    Sjölander, Arvid
    Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul
    Karolinska Institutet, Stockholm, Sweden.
    Oberg, A. Sara
    Karolinska Institutet, Stockholm, Sweden; Harvard T.H. Chan School of Public Health, Boston, USA.
    Translational Epidemiologic Approaches to Understanding the Consequences of Early-Life Exposures2016In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 46, no 3, p. 315-328Article, review/survey (Refereed)
    Abstract [en]

    Prominent developmental theories posit a causal link between early-life exposures and later functioning. Yet, observed associations with early exposures may not reflect causal effects because of genetic and environmental confounding. The current manuscript describes how a systematic series of epidemiologic analyses that combine several genetically-informative designs and statistical approaches can help distinguish between competing theories. In particular, the manuscript details how combining the use of measured covariates with sibling-comparisons, cousin-comparisons, and additional designs can help elucidate the sources of covariation between early-life exposures and later outcomes, including the roles of (a) factors that are not shared in families, including a potential causal effect of the exposure; (b) carryover effects from the exposure of one child to the next; and (c) familial confounding. We also describe key assumptions and how they can be critically evaluated. Furthermore, we outline how subsequent analyses, including effect decomposition with respect to measured, plausible mediators, and quantitative genetic models can help further specify the underlying processes that account for the associations between early-life exposures and offspring outcomes.

  • 247.
    Dorafshan Esfahani, Eshagh
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University.
    Methyltransferase Ash1, histone methylation and their impact on Polycomb repression2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Antagonistic interactions between Polycomb Group (PcG) and Trithorax Group (TrxG) proteins orchestrate the expression of key developmental genes. Distinct maternally loaded repressors establish the silenced state of these genes in cells where they should not be expressed and later PcG proteins sense whether a target gene is inactive and maintain the repression throughout multiple cell divisions. PcG proteins are targeted to genes by DNA elements called Polycomb Response Elements (PREs). The proteins form two major classes of complexes, namely Polycomb Repressive Complex 1 (PRC1) and Polycomb Repressive Complex 2 (PRC2). Mechanistic details of Polycomb repression are not fully understood, however, tri-methylation of Lysine 27 of histone H3 (H3K27me3) is essential for this process. Using Drosophila cell lines deficient for either PRC1 or PRC2, I investigated the role of H3K27 methylation and the interdependence of PRC1 complexes for their recruitment to PREs. My results indicate that recruitment of PcG complexes to PREs proceed via multiple pathways and that H3K27 methylation is not needed for their targeting. However, the methylation is required to stabilize interactions of PRE-anchored PcG complexes with surrounding chromatin.

    TrxG proteins prevent erroneous repression of Polycomb target genes where these genes need to be expressed. Ash1 is a TrxG protein which binds Polycomb target genes when they are transcriptionally active. It contains a SET domain which methylates Lysine 36 of histone H3 (H3K36). In vitro, histone H3 methylated at K36 is a poor substrate for H3K27 methylation by PRC2. This prompted a model where Ash1 counteracts Polycomb repression through H3K36 methylation. However, this model was never tested in vivo and does not consider several experimental observations. First, in the ash1 mutant flies the bulk H3K36me2/H3K36me3 levels remain unchanged. Second, in Drosophila, there are two other H3K36-specific histone methyltransferases, NSD and Set2, which should be capable to inhibit PRC2. Third, Ash1 contains multiple evolutionary conserved domains whose roles have not been investigated. Therefore, I asked whether H3K36 methylation is critical for Ash1 to counteract Polycomb repression in vivo and whether NSD and Set2 proteins contribute to this process. I used flies lacking endogenous histone genes and complemented them with transgenic histone genes where Lysine 36 is replaced by Arginine. In these animals, I assayed erroneous repression of HOX genes as a readout for erroneous Polycomb repression. I used the same readout in the NSD or Set2 mutant flies. I also asked if other conserved domains of Ash1 are essential for its function. In addition to SET and domain, Ash1 contains three AT hook motifs as well as BAH and PHD domains. I genetically complemented ash1 loss of function animals with transgenic Ash1 variants, in each, one domain of Ash1 is deleted. I found that Ash1 is the only H3K36-specific histone methyltransferase which counteracts Polycomb repression in Drosophila. My findings suggest that the model, where Ash1 counteracts PcG repression by inhibiting PRC2 via methylation of H3K36, has to be revised. I also showed that, in vivo, Ash1 acts as a multimer and requires SET, BAH and PHD domains to counteract Polycomb repression.

    This work led to two main conclusions. First, trimethylation of H3K27 is not essential for targeting PcG proteins to PREs but acts afterwards to stabilize their interaction with the chromatin of the neighboring genes. Second, while SET domain is essential for Ash1 to oppose Polycomb repression, methylation of H3K36 does not play a central role in the process.

    The full text will be freely available from 2019-12-18 00:01
  • 248.
    Dorafshan, Eshagh
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Kahn, Tatyana G.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Glotov, Alexander
    Savitsky, Mikhail
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Schwartz, Yuri B.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Functional dissection of Drosophila Ash1 domainsManuscript (preprint) (Other academic)
  • 249.
    Dorafshan, Eshagh
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Kahn, Tatyana G.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Glotov, Alexander
    Savitsky, Mikhail
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Walther, Matthias
    Reuter, Gunter
    Schwartz, Yuri B.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Does Ash1 counteract Polycomb repression by methylating H3K36?Manuscript (preprint) (Other academic)
    Abstract [en]

    Polycomb repression is critical to maintain cell type specific genome expression programs in a wide range of multicellular animals. Equally important but less studied is the Trithorax group system, which safeguards Polycomb target genes from the repression in cells where they have to remain active. Based on in vitro studies it was proposed that the Trithorax group system acts via methylation of histone H3 at Lysine 4 (H3K4) and Lysine 36 (H3K36) thereby inhibiting histone methyltransferase activity of the Polycomb complexes. This hypothesis is yet to be comprehensively tested in vivo. Here we used the power of the Drosophila model to investigate how the Trithorax group protein Ash1 and the H3K36 methylation counteract Polycomb repression. We show, for the first time, that Ash1 is the only Drosophila H3K36-specific methyltransferase required to prevent excessive Polycomb repression of homeotic genes. Unexpectedly, our experiments revealed no correlation between the extent of H3K36 methylation and the resistance to Polycomb repression. Furthermore, we find that complete substitution of the zygotic histone H3 with a variant in which Lysine 36 is replaced by Arginine does not cause excessive repression of Drosophila homeotic genes. Together with earlier studies, our results suggest that the model, where the Trithorax group proteins methylate histone H3 to inhibit the histone methyltransferase activity of the Polycomb complexes, may need to be reevaluated.

  • 250.
    Dowling, Damian K
    et al.
    Animal Ecology/Department of Ecology and Evolution, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Friberg, Urban
    Department of Ecology and Environmental Science, Umeå University, SE-901 87 Umeå , Sweden.
    Hailer, Frank
    Animal Ecology/Department of Ecology and Evolution, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Arnqvist, Göran
    Animal Ecology/Department of Ecology and Evolution, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Intergenomic epistasis for fitness: within-population interactions between cytoplasmic and nuclear genes in Drosophila melanogaster.2007In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 175, no 1, p. 235-44Article in journal (Refereed)
    Abstract [en]

    The symbiotic relationship between the mitochondrial and nuclear genomes coordinates metabolic energy production and is fundamental to life among eukaryotes. Consequently, there is potential for strong selection to shape interactions between these two genomes. Substantial research attention has focused on the possibility that within-population sequence polymorphism in mitochondrial DNA (mtDNA) is maintained by mitonuclear fitness interactions. Early theory predicted that selection will often eliminate mitochondrial polymorphisms. However, recent models demonstrate that intergenomic interactions can promote the maintenance of polymorphism, especially if the nuclear genes involved are linked to the X chromosome. Most empirical studies to date that have assessed cytonuclear fitness interactions have studied variation across populations and it is still unclear how general and strong such interactions are within populations. We experimentally tested for cytonuclear interactions within a laboratory population of Drosophila melanogaster using 25 randomly sampled cytoplasmic genomes, expressed in three different haploid nuclear genetic backgrounds, while eliminating confounding effects of intracellular bacteria (e.g., Wolbachia). We found sizable cytonuclear fitness interactions within this population and present limited evidence suggesting that these effects were sex specific. Moreover, the relative fitness of cytonuclear genotypes was environment specific. Sequencing of mtDNA (2752 bp) revealed polymorphism within the population, suggesting that the observed cytoplasmic genetic effects may be mitochondrial in origin.

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