Change search
Refine search result
2345678 201 - 250 of 1218
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 201. 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.

  • 202.
    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.

  • 203.
    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)
  • 204.
    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.

  • 205.
    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.

  • 206.
    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.

  • 207.
    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

  • 208.
    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.

  • 209.
    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.

  • 210. 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)
  • 211.
    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.

  • 212.
    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)
  • 213.
    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)
  • 214.
    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.

  • 215. 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.

  • 216.
    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.

  • 217.
    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.

  • 218.
    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.

  • 219.
    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.

  • 220. 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.

  • 221.
    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.

  • 222.
    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.

  • 223.
    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.

  • 224.
    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.

  • 225. 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.

  • 226. 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.

  • 227.
    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)
  • 228.
    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.

  • 229.
    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.

  • 230. 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.

  • 231.
    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.

     

  • 232. 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.

  • 233.
    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. 

  • 234.
    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.

  • 235. 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)
  • 236. 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)
  • 237.
    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.

  • 238.
    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.

  • 239.
    Dowling, Damian K.
    et al.
    Centre for Evolutionary Biology, School of Animal Biology (M092), The University of Western Australia, Crawley, WA, Australia / Animal Ecology/Department of Ecology and Evolution, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Friberg, Urban
    Department of Ecology, Evolution and Marine Biology, University of California, Santa Barbara, CA, USA.
    Lindell, Johan
    Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Evolutionary implications of non-neutral mitochondrial genetic variation2008In: Trends in Ecology & Evolution, ISSN 0169-5347, E-ISSN 1872-8383, Vol. 23, no 10, p. 546-554Article, review/survey (Refereed)
    Abstract [en]

    Sequence variation in mitochondrial DNA (mtDNA) was traditionally considered to be selectively neutral. However, an accumulating body of evidence indicates that this assumption is invalid. Furthermore, recent advances indicate that mtDNA polymorphism can be maintained within populations via selection on the joint mitochondrial-nuclear genotype. Here, we review the latest findings that show mitochondrial and cytoplasmic genetic variation for life-history traits and fitness. We highlight the key importance of the mitochondrial-nuclear interaction as a unit of selection and discuss the consequences of mitochondrially encoded fitness effects on several key evolutionary processes. Our goal is to draw attention to the profound, yet neglected, influence of the mitochondrial genome on the fields of ecology and evolution.

  • 240.
    Dragan, Smiljic
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Studies of small bicoid knock-down and overexpression at early and late stage of development in Drosophila melanogaster.2016Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
  • 241. Drotz, Marcus K
    et al.
    Brodin, Tomas
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Nilsson, Anders N
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Changing Names with Changed Address: Integrated Taxonomy and Species Delimitation in the Holarctic Colymbetes paykulli Group (Coleoptera: Dytiscidae)2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, article id e0143577Article in journal (Refereed)
    Abstract [en]

    Species delimitation of geographically isolated forms is a long-standing problem in less studied insect groups. Often taxonomic decisions are based directly on morphologic variation, and lack a discussion regarding sample size and the efficiency of migration barriers or dispersal/migration capacity of the studied species. These problems are here exemplified in a water beetle complex from the Bering Sea region that separates North America from Eurasia. Only a few sampled specimens occur from this particular area and they are mostly found in museum and private collections. Here we utilize the theory of integrated taxonomy to discuss the speciation of the Holarctic Colymbetes paykulli water beetle complex, which historically has included up to five species of which today only two are recognized. Three delimitation methods are used; landmark based morphometry of body shape, variation in reticulation patterns of the pronotum exo-skeleton and sequence variation of the partial mitochondrial gene Cyt b. Our conclusion is that the Palearctic and Nearctic populations of C. paykulli are given the status of separate species, based on the fact that all methods showed significant separation between populations. As a consequence the name of the Palearctic species is C. paykulli Erichson and the Nearctic species should be known as C. longulus LeConte. There is no clear support for delineation between Palearctic and Nearctic populations of C. dahuricus based on mtDNA. However, significant difference in size and reticulation patterns from the two regions is shown. The combined conclusion is that the C. dahuricus complex needs a more thorough investigation to fully disentangle its taxonomic status. Therefore it is here still regarded as a Holarctic species. This study highlights the importance to study several diagnosable characters that has the potential to discriminate evolutionary lineage during speciation.

  • 242. Du, Qingzhang
    et al.
    Tian, Jiaxing
    Yang, Xiaohui
    Pan, Wei
    Xu, Baohua
    Li, Bailian
    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).
    Zhang, Deqiang
    Identification of additive, dominant, and epistatic variation conferred by key genes in cellulose biosynthesis pathway in Populus tomentosa2015In: DNA research, ISSN 1340-2838, E-ISSN 1756-1663, Vol. 22, no 1, p. 53-67Article in journal (Refereed)
    Abstract [en]

    Economically important traits in many species generally show polygenic, quantitative inheritance. The components of genetic variation (additive, dominant and epistatic effects) of these traits conferred by multiple genes in shared biological pathways remain to be defined. Here, we investigated 11 full-length genes in cellulose biosynthesis, on 10 growth and wood-property traits, within a population of 460 unrelated Populus tomentosa individuals, via multi-gene association. To validate positive associations, we conducted single-marker analysis in a linkage population of 1,200 individuals. We identified 118, 121, and 43 associations (P < 0.01) corresponding to additive, dominant, and epistatic effects, respectively, with low to moderate proportions of phenotypic variance (R-2). Epistatic interaction models uncovered a combination of three non-synonymous sites from three unique genes, representing a significant epistasis for diameter at breast height and stem volume. Single-marker analysis validated 61 associations (false discovery rate, Q <= 0.10), representing 38 SNPs from nine genes, and its average effect (R-2 = 3.8%) nearly 2-fold higher than that identified with multi-gene association, suggesting that multi-gene association can capture smaller individual variants. Moreover, a structural gene-gene network based on tissue-specific transcript abundances provides a better understanding of the multi-gene pathway affecting tree growth and lignocellulose biosynthesis. Our study highlights the importance of pathway-based multiple gene associations to uncover the nature of genetic variance for quantitative traits and may drive novel progress in molecular breeding.

  • 243.
    Duan, Chen
    et al.
    Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Guo, Xiong
    Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Zhang, Xiao-Dong
    First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Yu, Han-Jie
    Northwest University, Xi'an, Shaanxi, China.
    Yan, Hua
    Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Gao, Ying
    Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Ma, Wei-Juan
    Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Gao, Zong-Qiang
    Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    Xu, Peng
    Xi'an Red Cross Hospital, Xi'an, Shaanxi, China.
    Lammi, Mikko
    University of Kuopio, Kuopio, Finland.
    Comparative analysis of gene expression profiles between primary knee osteoarthritis and an osteoarthritis endemic to Northwestern China, Kashin-Beck disease.2010In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, no 3, p. 771-780, article id 20131229Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the differences in gene expression profiles of adult articular cartilage from patients with Kashin-Beck disease (KBD) versus those with primary knee osteoarthritis (OA).

    METHODS: The messenger RNA expression profiles of articular cartilage from patients with KBD, diagnosed according to the clinical criteria for KBD in China, were compared with those of cartilage from patients with OA, diagnosed according to the Western Ontario and McMaster Universities OA Index. Total RNA was isolated separately from 4 pairs of the KBD and OA cartilage samples, and the expression profiles were evaluated by Agilent 4x44k Whole Human Genome density oligonucleotide microarray analysis. The microarray data for selected transcripts were confirmed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) amplification.

    RESULTS: For 1.2 x 10(4) transcripts, corresponding to 58.4% of the expressed transcripts, 2-fold changes in differential expression were revealed. Expression levels higher in KBD than in OA samples were observed in a mean + or - SD 6,439 + or - 1,041 (14.6 + or - 2.4%) of the transcripts, and expression levels were lower in KBD than in OA samples in 6,147 + or - 1,222 (14.2 + or - 2.8%) of the transcripts. After application of the selection criteria, 1.85% of the differentially expressed genes (P < 0.001 between groups) were detected. These included 233 genes, of which 195 (0.4%) were expressed at higher levels and 38 (0.08%) were expressed at lower levels in KBD than in OA cartilage. Comparisons of the quantitative RT-PCR data supported the validity of our microarray data.

    CONCLUSION: Differences between KBD and OA cartilage exhibited a similar pattern among all 4 of the pairs examined, indicating the presence of disease mechanisms, mainly chondrocyte matrix metabolism, cartilage degeneration, and apoptosis induction pathways, which contribute to cartilage destruction in KBD.

  • 244. Dudgeon, Crissy
    et al.
    Shreeram, Sathyavageeswaran
    Tanoue, Kan
    Mazur, Sharlyn J
    Sayadi, Ahmed
    Institute of Molecular and Cell Biology; Proteos; Singapore.
    Robinson, Robert C
    Appella, Ettore
    Bulavin, Dmitry V
    Genetic variants and mutations of PPM1D control the response to DNA damage2013In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 12, no 16Article in journal (Refereed)
    Abstract [en]

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

  • 245. Eisfeldt, Jesper
    et al.
    Nazaryan-Petersen, Lusine
    Lundin, Johanna Lundin
    Pettersson, Maria
    Nilsson, Daniel
    Wincent, Josephine
    Lieden, Agne
    Vezzi, Francesco
    Wirta, Valteri
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Käller, Max
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Duelund, Tina
    Houssari, Rayan
    Pignata, Laura
    Bak, Mads
    Tommerup, Niels
    Lundberg, Elisabeth Syk
    Tumer, Zeynep
    Lindstrand, Anna
    Whole genome characterization of array defined clustered CNVs reveals two distinct complex rearrangement subclasses generated through either non homologous repair or template switching2017In: Molecular Cytogenetics, ISSN 1755-8166, E-ISSN 1755-8166, Vol. 10Article in journal (Other academic)
  • 246. Ek, Weronica
    et al.
    Sahlqvist, Anna-Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Crooks, Lucy
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Sgonc, Roswitha
    Dietrich, Hermann
    Wick, Georg
    Ekwall, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Carlborg, Örjan
    Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Kerje, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mapping QTL affecting a systemic sclerosis-like disorder in a cross between UCD-200 and red jungle fowl chickens2012In: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 38, no 2, p. 352-359Article in journal (Refereed)
    Abstract [en]

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

  • 247.
    Ekblom, Robert
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Biao, Wang
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala Univ, Dept Ecol & Genet, Evolutionary Biol Ctr, Norbyvagen 18D, S-75236 Uppsala, Sweden..
    Development of transcriptome genetic markers for the great snipe (Gallinago media)2017In: Conservation Genetics Resources, ISSN 1877-7252, E-ISSN 1877-7260, Vol. 9, no 4, p. 643-645Article in journal (Refereed)
    Abstract [en]

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

  • 248.
    Ekblom, Robert
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Slate, Jon
    Horsburgh, Gavin J
    Birkhead, Tom
    Burke, Terry
    Comparison between Normalised and Unnormalised 454-Sequencing Libraries for Small-Scale RNA-Seq Studies2012In: Comparative and functional genomics, ISSN 1531-6912, E-ISSN 1532-6268, Vol. 2012, p. 281693-Article in journal (Refereed)
    Abstract [en]

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

  • 249.
    Ekblom, Robert
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Population Biology.
    Sæther, Stein Are
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Population Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Evolutionary Biology.
    Grahn, Mats
    Fiske, Peder
    Kålås, John Atle
    Höglund, Jacob
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Population Biology.
    Major histocompatibility complex variation and mate choice in a lekking bird, the great snipe (Gallinago media)2004In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 13, no 12, p. 3821-3828Article in journal (Refereed)
    Abstract [en]

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

  • 250.
    Ekblom, Robert
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Wennekes, Paul
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Horsburgh, Gavin J.
    Burke, Terry
    Characterization of the house sparrow (Passer domesticus) transcriptome: a resource for molecular ecology and immunogenetics2014In: Molecular Ecology Resources, ISSN 1755-098X, E-ISSN 1755-0998, Vol. 14, no 3, p. 636-646Article in journal (Refereed)
    Abstract [en]

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

2345678 201 - 250 of 1218
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf