Digitala Vetenskapliga Arkivet

Endre søk
Begrens søket
2345678 201 - 250 of 1525
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 201.
    Castroviejo-Fisher, Santiago
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Skoglund, Pontus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Valadez, Raul
    Laboratorio de Paleozoología, Instituto de Investigaciones Antropológicas, Universidad Nacional Autónoma de México.
    Vilá, Carles
    Conservation and Evolutionary Genetics Group, Estación Biológica de Doñana (EBD-CSIC).
    Leonard, Jennifer A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Vanishing Native American dog lineages2011Inngår i: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 11, s. 73-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Dogs were an important element in many native American cultures at the time Europeans arrived. Although previous ancient DNA studies revealed the existence of unique native American mitochondrial sequences, these have not been found in modern dogs, mainly purebred, studied so far.

    Results: We identified many previously undescribed mitochondrial control region sequences in 400 dogs from rural and isolated areas as well as street dogs from across the Americas. However, sequences of native American origin proved to be exceedingly rare, and we estimate that the native population contributed only a minor fraction of the gene pool that constitutes the modern population.

    Conclusions: The high number of previously unidentified haplotypes in our sample suggests that a lot of unsampled genetic variation exists in non-breed dogs. Our results also suggest that the arrival of European colonists to the Americas may have led to an extensive replacement of the native American dog population by the dogs of the invaders.

  • 202.
    Catalan, Ana
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi. Ludwig Maximilians Univ Munchen, Div Evolutionary Biol, D-82152 Planegg Martinsried, Germany.
    Briscoe, Adriana D.
    Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92697 USA.
    Hohna, Sebastian
    Ludwig Maximilians Univ Munchen, Div Evolutionary Biol, D-82152 Planegg Martinsried, Germany;Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92697 USA;Ludwig Maximilians Univ Munchen, Dept Earth & Environm Sci Paleontol & Geobiol, D-80333 Munich, Germany;Ludwig Maximilians Univ Munchen, GeoBio Ctr, D-80333 Munich, Germany.
    Drift and Directional Selection Are the Evolutionary Forces Driving Gene Expression Divergence in Eye and Brain Tissue of Heliconius Butterflies2019Inngår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 213, nr 2, s. 581-594Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Investigating gene expression evolution over micro- and macroevolutionary timescales will expand our understanding of the role of gene expression in adaptation and speciation. In this study, we characterized the evolutionary forces acting on gene expression levels in eye and brain tissue of five Heliconius butterflies with divergence times of similar to 5-12 MYA. We developed and applied Brownian motion (BM) and Ornstein-Uhlenbeck (OU) models to identify genes whose expression levels are evolving through drift, stabilizing selection, or a lineage-specific shift. We found that 81% of the genes evolve under genetic drift. When testing for branch-specific shifts in gene expression, we detected 368 (16%) shift events. Genes showing a shift toward upregulation have significantly lower gene expression variance than those genes showing a shift leading toward downregulation. We hypothesize that directional selection is acting in shifts causing upregulation, since transcription is costly. We further uncovered through simulations that parameter estimation of OU models is biased when using small phylogenies and only becomes reliable with phylogenies having >= 50 taxa. Therefore, we developed a new statistical test based on BM to identify highly conserved genes (i.e., evolving under strong stabilizing selection), which comprised 3% of the orthoclusters. In conclusion, we found that drift is the dominant evolutionary force driving gene expression evolution in eye and brain tissue in Heliconius. Nevertheless, the higher proportion of genes evolving under directional than under stabilizing selection might reflect species-specific selective pressures on vision and the brain that are necessary to fulfill species-specific requirements. Characterization of gene expression patterns across species - and the evolutionary forces driving them - can reveal processes that have remained conserved across species, as well as those that have changed in a species- specific manner...

    Fulltekst (pdf)
    FULLTEXT01
  • 203. Catania, Francesco
    et al.
    Gao, Xiang
    Scofield, Douglas
    Endogenous Mechanisms for the Origins of Spliceosomal Introns2009Inngår i: Journal of Heredity, ISSN 0022-1503, E-ISSN 1465-7333, Vol. 100, nr 5, s. 591-596Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Over 30 years since their discovery, the origin of spliceosomal introns remains uncertain. One nearly universally accepted hypothesis maintains that spliceosomal introns originated from self-splicing group-II introns that invaded the uninterrupted genes of the last eukaryotic common ancestor (LECA) and proliferated by “insertion” events. Although this is a possible explanation for the original presence of introns and splicing machinery, the emphasis on a high number of insertion events in the genome of the LECA neglects a considerable body of empirical evidence showing that spliceosomal introns can simply arise from coding or, more generally, nonintronic sequences within genes. After presenting a concise overview of some of the most common hypotheses and mechanisms for intron origin, we propose two further hypotheses that are broadly based on central cellular processes: 1) internal gene duplication and 2) the response to aberrant and fortuitously spliced transcripts. These two nonmutually exclusive hypotheses provide a powerful way to explain the establishment of spliceosomal introns in eukaryotes without invoking an exogenous source.

  • 204.
    Cavalli, Marco
    et al.
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Baltzer, Nicholas
    Uppsala Univ, Dept Cell & Mol Biol Computat Biol & Bioinformat, Uppsala, Sweden..
    Umer, Husen M.
    Uppsala Univ, Dept Cell & Mol Biol Computat Biol & Bioinformat, Uppsala, Sweden..
    Grau, Jan
    Martin Luther Univ Halle Wittenberg, Inst Comp Sci, Halle, Germany..
    Lemnian, Ioana
    Martin Luther Univ Halle Wittenberg, Inst Comp Sci, Halle, Germany..
    Pan, Gang
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Wallerman, Ola
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Spalinskas, Rapolas
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Sahlén, Pelin
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Grosse, Ivo
    Martin Luther Univ Halle Wittenberg, Inst Comp Sci, Halle, Germany.;German Ctr Integrat Biodivers Res iDiv, Leipzig, Germany..
    Komorowski, Jan
    Uppsala Univ, Dept Cell & Mol Biol Computat Biol & Bioinformat, Uppsala, Sweden.;Polish Acad Sci, Inst Comp Sci, Warsaw, Poland..
    Wadelius, Claes
    Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Allele specific chromatin signals, 3D interactions, and motif predictions for immune and B cell related diseases2019Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 2695Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Several Genome Wide Association Studies (GWAS) have reported variants associated to immune diseases. However, the identified variants are rarely the drivers of the associations and the molecular mechanisms behind the genetic contributions remain poorly understood. ChIP-seq data for TFs and histone modifications provide snapshots of protein-DNA interactions allowing the identification of heterozygous SNPs showing significant allele specific signals (AS-SNPs). AS-SNPs can change a TF binding site resulting in altered gene regulation and are primary candidates to explain associations observed in GWAS and expression studies. We identified 17,293 unique AS-SNPs across 7 lymphoblastoid cell lines. In this set of cell lines we interrogated 85% of common genetic variants in the population for potential regulatory effect and we identified 237 AS-SNPs associated to immune GWAS traits and 714 to gene expression in B cells. To elucidate possible regulatory mechanisms we integrated long-range 3D interactions data to identify putative target genes and motif predictions to identify TFs whose binding may be affected by AS-SNPs yielding a collection of 173 AS-SNPs associated to gene expression and 60 to B cell related traits. We present a systems strategy to find functional gene regulatory variants, the TFs that bind differentially between alleles and novel strategies to detect the regulated genes.

  • 205. Cavelier, L
    et al.
    Erikson, I
    Tammi, M
    Jalonen, P
    Lindholm, Eva
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Evolutionsbiologi.
    Jazin, Elena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Evolutionsbiologi.
    Smith, P
    Luthman, H
    Gyllensten, U
    MtDNA mutations in maternally inherited diabetes: presence of the 3397 ND1 mutation previously associated with Alzheimer's and Parkinson's disease2001Inngår i: Hereditas, ISSN 0018-0661, E-ISSN 1601-5223, Vol. 135, nr 1, s. 65-70Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mutations in the mitochondrial tRNA(leu) (UUR) gene have been associated with diabetes mellitus and deafness. We screened for the presence of mtDNA mutations in the tRNA(leu) (UUR) gene and adjacent ND1 sequences in 12 diabetes mellitus pedigrees with a possible maternal inheritance of the disease. One patient carried a G to A substitution at nt 3243 (tRNA(leu) (UUR) gene) in heteroplasmic state. In a second pedigree a patient had an A to G substitution at nt 3397 in the ND1 gene. All maternal relatives of the proband had the 3397 substitution in homoplasmic state. This substitution was not present in 246 nonsymptomatic Caucasian controls. The 3397 substitution changes a highly conserved methionine to a valine at aa 31 and has previously been found in Alzheimer's (AD) and Parkinson's (PD) disease patients. Substitutions in the mitochondrial ND1 gene at aa 30 and 31 have associated with a number of different diseases (e.g. AD/PD, MELAS, cardiomyopathy and diabetes mellitus, LHON, Wolfram-syndrome and maternal inherited diabetes) suggesting that changes at these two codons may be associated with very diverse pathogenic processes. In a further attempt to search for mtDNA mutations outside the tRNAleu gene associated with diabetes, the whole mtDNA genome sequence was determined for two patients with maternally inherited diabetes and deafness. Except for substitutions previously reported as polymorphisms, none of the two patients showed any non-synonymous substitutions either in homoplasmic or heteroplasmic state. These results imply that the maternal inherited diabetes and deafness in these patients must result from alterations of nuclear genes and/or environmental factors.

  • 206.
    Cederlöf, Martin
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Pettersson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sariaslan, Amir
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Östberg, Per
    Division of Speech and Language Pathology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Speech and Language Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Kelleher, Ian
    Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
    Långström, Niklas
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; R&D unit, Swedish Prison and Probation Service, Stockholm, Sweden.
    Gumpert, Clara Hellner
    Centre for Psychiatry Research & Education, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm County Council, Stockholm, Sweden.
    Lundström, Sebastian
    Centre for Ethics, Law and Mental Health (CELAM), University of Gothenburg, Gothenburg, Sweden; Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    The association between childhood autistic traits and adolescent psychotic experiences is explained by general neuropsychiatric problems.2016Inngår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 171, nr 2, s. 153-159Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Studies suggest associations between childhood autistic traits and adolescent psychotic experiences. However, recent research suggests that a general neuropsychiatric problems factor predicts adverse outcomes better than specific diagnostic entities. To examine if the alleged association between autistic traits and psychotic experiences could rather be explained by a general neuropsychiatric problems factor comprising symptoms of ADHD, tic disorder, developmental coordination disorder, and learning disorder, we conducted a prospective cohort study based on the Child and Adolescent Twin Study in Sweden. In addition, we examined the genetic and environmental influences on the associations. A total of 9,282 twins with data on childhood autistic traits and other neuropsychiatric problems, and follow-up data on psychotic experiences at ages 15 and/or 18 years were included. First, psychotic experiences were regressed on autistic traits and second, the general neuropsychiatric problems factor was added to the model. Auditory hallucinations were analyzed separately from the other psychotic experiences. Finally, twin analyses were employed to disentangle genetic from environmental influences in the observed associations. Replicating prior research, significant associations were found between autistic traits in childhood and auditory hallucinations at ages 15 and 18. However, after controlling for the general neuropsychiatric problems factor, the associations between autistic traits and auditory hallucinations disappeared, whereas the association between the general neuropsychiatric problems factor and auditory hallucinations persisted after controlling for autistic traits. Twin analyses revealed that the association between the general neuropsychiatric problems factor and auditory hallucinations was driven by shared genetic influences. .

  • 207.
    Celorio-Mancera, Maria de la Paz
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Zoologiska institutionen.
    Ahn, Seung-Joon
    Vogel, Heiko
    Heckel, David G.
    Transcriptional responses underlying the hormetic and detrimental effects of the plant secondary metabolite gossypol on the generalist herbivore Helicoverpa armigera2011Inngår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 12, s. 575-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Hormesis is a biphasic biological response characterized by the stimulatory effect at relatively low amounts of chemical compounds which are otherwise detrimental at higher concentrations. A hormetic response in larval growth rates has been observed in cotton-feeding insects in response to increasing concentrations of gossypol, a toxic metabolite found in the pigment glands of some plants in the family Malvaceae. We investigated the developmental effect of gossypol in the cotton bollworm, Helicoverpa armigera, an important heliothine pest species, by exposing larvae to different doses of this metabolite in their diet. In addition, we sought to determine the underlying transcriptional responses to different gossypol doses. Results: Larval weight gain, pupal weight and larval development time were measured in feeding experiments and a hormetic response was seen for the first two characters. On the basis of net larval weight gain responses to gossypol, three concentrations (0%, 0.016% and 0.16%) were selected for transcript profiling in the gut and the rest of the body in a two-color double reference design microarray experiment. Hormesis could be observed at the transcript level, since at the low gossypol dose, genes involved in energy acquisition such as beta-fructofuranosidases were up-regulated in the gut, and genes involved in cell adhesion were down-regulated in the body. Genes with products predicted to be integral to the membrane or associated with the proteasome core complex were significantly affected by the detrimental dose treatment in the body. Oxidoreductase activity-related genes were observed to be significantly altered in both tissues at the highest gossypol dose. Conclusions: This study represents the first transcriptional profiling approach investigating the effects of different concentrations of gossypol in a lepidopteran species. H. armigera's transcriptional response to gossypol feeding is tissue-and dose-dependent and involves diverse detoxifying mechanisms not only to alleviate direct effects of gossypol but also indirect damage such as pH disturbance and oxygen radical formation. Genes discovered through this transcriptional approach may be additional candidates for understanding gossypol detoxification and coping with gossypol-induced stress. In a generalist herbivore that has evolved transcriptionally-regulated responses to a variety of different plant compounds, hormesis may be due to a lower induction threshold of growth-promoting, stress-coping responses and a higher induction threshold of detoxification pathways that are costly and cause collateral damage to the cell.

  • 208.
    Ceplitis, H.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    Ellegren, H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Institutionen för evolution, genomik och systematik, Evolutionsbiologi. Evolutionsbiologi.
    Adaptive molecula evolution in HINTW, a female-specific gene in birds.2004Inngår i: Molecular Biology and Evolution, nr 21, s. 249-254Artikkel i tidsskrift (Fagfellevurdert)
  • 209.
    Chaillou, Thomas
    et al.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Malgoyre, A.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Banzet, S.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Chapot, R.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Koulmann, N.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Pugnière, P.
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Beaudry, M.
    Laboratoire Réponses Cellulaires et Fonctionnelles À l'Hypoxie, Université Paris, Bobigny, France.
    Bigard, X.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Peinnequin, A.
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Pitfalls in target mRNA quantification for real-time quantitative RT-PCR in overload-induced skeletal muscle hypertrophy2011Inngår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, nr 4, s. 228-235Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Quantifying target mRNA using real-time quantitative reverse transcription-polymerase chain reaction requires an accurate normalization method. Determination of normalization factors (NFs) based on validated reference genes according to their relative stability is currently the best standard method in most usual situations. This method controls for technical errors, but its physiological relevance requires constant NF values for a fixed weight of tissue. In the functional overload model, the increase in the total RNA concentration must be considered in determining the NF values. Here, we pointed out a limitation of the classical geNorm-derived normalization. geNorm software selected reference genes despite that the NF values extensively varied under experiment. Only the NF values calculated from four intentionally selected genes were constant between groups. However, a normalization based on these genes is questionable. Indeed, three out of four genes belong to the same functional class (negative regulator of muscle mass), and their use is physiological nonsense in a hypertrophic model. Thus, we proposed guidelines for optimizing target mRNA normalization and quantification, useful in models of muscle mass modulation. In our study, the normalization method by multiple reference genes was not appropriate to compare target mRNA levels between overloaded and control muscles. A solution should be to use an absolute quantification of target mRNAs per unit weight of tissue, without any internal normalization. Even if the technical variations will stay present as a part of the intergroup variations, leading to less statistical power, we consider this method acceptable because it will not generate misleading results.

  • 210.
    Charpentier, Emmanuelle
    et al.
    Department of Regulation in Infection Biology, Max Planck Institute for Infection Biology.
    Hess, Wolfgang R
    RNA in bacteria: biogenesis, regulatory mechanisms and functions2015Inngår i: FEMS Microbiology Reviews, ISSN 0168-6445, E-ISSN 1574-6976, Vol. 39, nr 3, s. 277-279Artikkel i tidsskrift (Fagfellevurdert)
  • 211.
    Chen, Changchun
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Huang, Bo
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Anderson, James T
    Byström, Anders S
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Unexpected accumulation of ncm5U and ncm5s2U in a trm9 mutant suggests an additional step in the synthesis of mcm5U and mcm5s2U.2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 6, s. e20783-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Transfer RNAs are synthesized as a primary transcript that is processed to produce a mature tRNA. As part of the maturation process, a subset of the nucleosides are modified. Modifications in the anticodon region often modulate the decoding ability of the tRNA. At position 34, the majority of yeast cytosolic tRNA species that have a uridine are modified to 5-carbamoylmethyluridine (ncm(5)U), 5-carbamoylmethyl-2'-O-methyluridine (ncm(5)Um), 5-methoxycarbonylmethyl-uridine (mcm(5)U) or 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U). The formation of mcm(5) and ncm(5) side chains involves a complex pathway, where the last step in formation of mcm(5) is a methyl esterification of cm(5) dependent on the Trm9 and Trm112 proteins.

    METHODOLOGY AND PRINCIPAL FINDINGS: Both Trm9 and Trm112 are required for the last step in formation of mcm(5) side chains at wobble uridines. By co-expressing a histidine-tagged Trm9p together with a native Trm112p in E. coli, these two proteins purified as a complex. The presence of Trm112p dramatically improves the methyltransferase activity of Trm9p in vitro. Single tRNA species that normally contain mcm(5)U or mcm(5)s(2)U nucleosides were isolated from trm9Δ or trm112Δ mutants and the presence of modified nucleosides was analyzed by HPLC. In both mutants, mcm(5)U and mcm(5)s(2)U nucleosides are absent in tRNAs and the major intermediates accumulating were ncm(5)U and ncm(5)s(2)U, not the expected cm(5)U and cm(5)s(2)U.

    CONCLUSIONS: Trm9p and Trm112p function together at the final step in formation of mcm(5)U in tRNA by using the intermediate cm(5)U as a substrate. In tRNA isolated from trm9Δ and trm112Δ strains, ncm(5)U and ncm(5)s(2)U nucleosides accumulate, questioning the order of nucleoside intermediate formation of the mcm(5) side chain. We propose two alternative explanations for this observation. One is that the intermediate cm(5)U is generated from ncm(5)U by a yet unknown mechanism and the other is that cm(5)U is formed before ncm(5)U and mcm(5)U.

    Fulltekst (pdf)
    fulltext
  • 212.
    Chen, Changchun
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Huang, Bo
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Eliasson, Mattias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Rydén, Patrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Byström, Anders S
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Elongator Complex Influences Telomeric Gene Silencing and DNA Damage Response by Its Role in Wobble Uridine tRNA Modification2011Inngår i: PLoS genetics, ISSN 1553-7404, Vol. 7, nr 9, s. e1002258-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Elongator complex is required for formation of the side chains at position 5 of modified nucleosides 5-carbamoylmethyluridine (ncm(5)U(34)), 5-methoxycarbonylmethyluridine (mcm(5)U(34)), and 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U(34)) at wobble position in tRNA. These modified nucleosides are important for efficient decoding during translation. In a recent publication, Elongator complex was implicated to participate in telomeric gene silencing and DNA damage response by interacting with proliferating cell nuclear antigen (PCNA). Here we show that elevated levels of tRNA(Lys) (s(2) ) (UUU), tRNA(Gln) (s(2) ) (UUG), and tRNA(Glu) (s(2) ) (UUC), which in a wild-type background contain the mcm(5)s(2)U nucleoside at position 34, suppress the defects in telomeric gene silencing and DNA damage response observed in the Elongator mutants. We also found that the reported differences in telomeric gene silencing and DNA damage response of various elp3 alleles correlated with the levels of modified nucleosides at U(34). Defects in telomeric gene silencing and DNA damage response are also observed in strains with the tuc2Δ mutation, which abolish the formation of the 2-thio group of the mcm(5)s(2)U nucleoside in tRNA(Lys) (mcm(5) (s(2) ) (UUU) ), tRNA(Gln) (mcm(5) (s(2) ) (UUG) ), and tRNA(Glu) (mcm(5) (s(2) ) (UUC) ). These observations show that Elongator complex does not directly participate in telomeric gene silencing and DNA damage response, but rather that modified nucleosides at U(34) are important for efficient expression of gene products involved in these processes. Consistent with this notion, we found that expression of Sir4, a silent information regulator required for assembly of silent chromatin at telomeres, was decreased in the elp3Δ mutants.

    Fulltekst (pdf)
    fulltext
  • 213.
    Chen, Jenny
    et al.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
    Swofford, Ross
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Johnson, Jeremy
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Cummings, Beryl B.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Harvard Med Sch, Program Biol & Biomed Sci, Boston, MA 02115 USA.
    Rogel, Noga
    Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 USA.
    Lindblad-Toh, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Haerty, Wilfried
    Earlham Inst, Norwich NR4 7UZ, Norfolk, England.
    di Palma, Federica
    Earlham Inst, Norwich NR4 7UZ, Norfolk, England;Univ East Anglia, Dept Biol & Med Sci, Norwich NR4 7TJ, Norfolk, England.
    Regev, Aviv
    Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 USA;MIT, Dept Biol, Cambridge, MA 02142 USA;MIT, Koch Inst, Cambridge, MA 02142 USA;Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
    A quantitative framework for characterizing the evolutionary history of mammalian gene expression2019Inngår i: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 29, nr 1, s. 53-63Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The evolutionary history of a gene helps predict its function and relationship to phenotypic traits. Although sequence conservation is commonly used to decipher gene function and assess medical relevance, methods for functional inference from comparative expression data are lacking. Here, we use RNA-seq across seven tissues from 17 mammalian species to show that expression evolution across mammals is accurately modeled by the Ornstein-Uhlenbeck process, a commonly proposed model of continuous trait evolution. We apply this model to identify expression pathways under neutral, stabilizing, and directional selection. We further demonstrate novel applications of this model to quantify the extent of stabilizing selection on a gene's expression, parameterize the distribution of each gene's optimal expression level, and detect deleterious expression levels in expression data from individual patients. Our work provides a statistical framework for interpreting expression data across species and in disease.

    Fulltekst (pdf)
    fulltext
  • 214.
    Chen, Jun
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Conifer Evolution, from Demography and Local Adaptation to Evolutionary Rates: Examples from the Picea genus2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Evolutionary process can be inferred at three different levels: the species level, the population level and the molecular level. In this thesis, I applied approaches at these three levels and aimed to get a comprehensive picture of conifer evolution, from speciation and demography to geographic variation and local adaptation, and then to the molecular evolution of proteins and small regulatory RNAs.

    Spruce species have been observed to possess a large number of trans-species shared polymorphisms. Using an “Isolation with migration” model, we found that the large effective population size of spruce retained these shared polymorphisms, inheriting them from the common ancestor. Post-divergence gene flow only existed between Picea abies and P. glauca, and between P. wilsonii and P. schrenkiana. The combination of Tajima’s D and Fay & Wu’s H at most of loci suggested an ancient and severe bottleneck for most species except P. breweriana.

    Furthermore, I investigated the effect of local selection in two parallel clines, which is one of the major forces that can cause divergence or even speciation. The timing of bud set and growth cessation was found correlated with latitude in populations of P. abies and P. obovata. Using allele frequency spectrum analyses we identified three genes under local selection in both species including two circadian-clock genes GI and PRR7, and one photoperiodic gene FTL2. This indicated that parallel evolution could occur through groups of genes within related pathways. Clinal variation at expression level provided stronger evidence of selection in FTL2, which has previously been associated with bud set in P. abies.

    Finally we focused on the molecular evolution of mRNA and small regulatory RNAs in P. abies. With the help of Next-Generation sequencing, we have achieved in spruce the first de novel assembly of the needle transcriptome and a preliminary characterization of sRNA populations. Along with features common in plants, spruce also exhibited novelties in many aspects including lower substitution rate and protein evolutionary rate, dominance of 21-nt sRNA, and a large proportion of TIR-NBS-LRR genes as sRNA sources and targets.

    Fulltekst (pdf)
    fulltext
  • 215.
    Chen, Jun
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Källman, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Ma, Xiaofei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Gyllenstrand, Niclas
    Zaina, Giusi
    Morgante, Michele
    Bousquet, Jean
    Eckert, Andrew
    Wegrzyn, Jill
    Neale, David
    Lagercrantz, Ulf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Lascoux, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Disentangling the Roles of History and Local Selection in Shaping Clinal Variation of Allele Frequencies and Gene Expression in Norway Spruce (Picea abies)2012Inngår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 191, nr 3, s. 865-881Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Understanding the genetic basis of local adaptation is challenging due to the subtle balance among conflicting evolutionary forces that are involved in its establishment and maintenance. One system with which to tease apart these difficulties is clines in adaptive characters. Here we analyzed genetic and phenotypic variation in bud set, a highly heritable and adaptive trait, among 18 populations of Norway spruce (Picea abies), arrayed along a latitudinal gradient ranging from 47°N to 68°N. We confirmed that variation in bud set is strongly clinal, using a subset of five populations. Genotypes for 137 single-nucleotide polymorphisms (SNPs) chosen from 18 candidate genes putatively affecting bud set and 308 control SNPs chosen from 264 random genes were analyzed for patterns of genetic structure and correlation to environment. Population genetic structure was low (F(ST) = 0.05), but latitudinal patterns were apparent among Scandinavian populations. Hence, part of the observed clinal variation should be attributable to population demography. Conditional on patterns of genetic structure, there was enrichment of SNPs within candidate genes for correlations with latitude. Twenty-nine SNPs were also outliers with respect to F(ST). The enrichment for clinal variation at SNPs within candidate genes (i.e., SNPs in PaGI, PaPhyP, PaPhyN, PaPRR7, and PaFTL2) indicated that local selection in the 18 populations, and/or selection in the ancestral populations from which they were recently derived, shaped the observed cline. Validation of these genes using expression studies also revealed that PaFTL2 expression is significantly associated with latitude, thereby confirming the central role played by this gene in the control of phenology in plants.

  • 216.
    Chen, Jun
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Källman, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Ma, Xiao-Fei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution. Chinese Acad Sci, Key Lab Stress Physiol & Ecol Cold & Arid Reg, Lanzhou, Peoples R China..
    Zaina, Giusi
    Univ Udine, Dept Agr Food Environm & Anim Sci, I-33100 Udine, Italy..
    Morgante, Michele
    Univ Udine, Dept Agr Food Environm & Anim Sci, I-33100 Udine, Italy..
    Lascoux, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Identifying Genetic Signatures of Natural Selection Using Pooled Population Sequencing in Picea abies2016Inngår i: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 6, nr 7, s. 1979-1989Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The joint inference of selection and past demography remain a costly and demanding task. We used next generation sequencing of two pools of 48 Norway spruce mother trees, one corresponding to the Fennoscandian domain, and the other to the Alpine domain, to assess nucleotide polymorphism at 88 nuclear genes. These genes are candidate genes for phenological traits, and most belong to the photoperiod pathway. Estimates of population genetic summary statistics from the pooled data are similar to previous estimates, suggesting that pooled sequencing is reliable. The nonsynonymous SNPs tended to have both lower frequency differences and lower F-ST values between the two domains than silent ones. These results suggest the presence of purifying selection. The divergence between the two domains based on synonymous changes was around 5 million yr, a time similar to a recent phylogenetic estimate of 6 million yr, but much larger than earlier estimates based on isozymes. Two approaches, one of them novel and that considers both F-ST and difference in allele frequencies between the two domains, were used to identify SNPs potentially under diversifying selection. SNPs from around 20 genes were detected, including genes previously identified as main target for selection, such as PaPRR3 and PaGI.

    Fulltekst (pdf)
    fulltext
  • 217.
    Chen, Jun
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Tsuda, Yoshiaki
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Stocks, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Kallman, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Xu, Nannan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Karkkainen, Katri
    Huotari, Tea
    Semerikov, Vladimir L.
    Vendramin, Giovanni G.
    Lascoux, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Clinal Variation at Phenology-Related Genes in Spruce: Parallel Evolution in FTL2 and Gigantea?2014Inngår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 197, nr 3, s. 1025-1038Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Parallel clines in different species, or in different geographical regions of the same species, are an important source of information on the genetic basis of local adaptation. We recently detected latitudinal clines in SNPs frequencies and gene expression of candidate genes for growth cessation in Scandinavian populations of Norway spruce (Picea abies). Here we test whether the same clines are also present in Siberian spruce (P. obovata), a close relative of Norway spruce with a different Quaternary history. We sequenced nine candidate genes and 27 control loci and genotyped 14 SSR loci in six populations of P. obovata located along the Yenisei river from latitude 56 N to latitude 67 N. In contrast to Scandinavian Norway spruce that both departs from the standard neutral model (SNM) and shows a clear population structure, Siberian spruce populations along the Yenisei do not depart from the SNM and are genetically unstructured. Nonetheless, as in Norway spruce, growth cessation is significantly clinal. Polymorphisms in photoperiodic (FTL2) and circadian clock (Gigantea, GI, PRR3) genes also show significant clinal variation and/or evidence of local selection. In GI, one of the variants is the same as in Norway spruce. Finally, a strong cline in gene expression is observed for FTL2, but not for GI. These results, together with recent physiological studies, confirm the key role played by FTL2 and circadian clock genes in the control of growth cessation in spruce species and suggest the presence of parallel adaptation in these two species.

  • 218.
    Chen, Jun
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Tsuda, Yoshiaki
    CNR, Plant Genetics Institute, Sesto Fiorentino, Firenze, Italy.
    Stocks, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Källman, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Semerikov, Vladimir
    Institute of Plant and Animal Ecology, Ural Division of the Russian Academy of Sciences.
    Vendramin, Giovanni
    CNR, Plant Genetics Institute, Sesto Fiorentino, Firenze, Italy.
    Lascoux, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Clinal variation in allele frequency at photoperiodic genes in Siberian spruce: an example of convergent evolution?Manuskript (preprint) (Annet vitenskapelig)
  • 219.
    Chen, Jun
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Tsuda, Yoshiaki
    CNR, Plant Genetics Institute, Sesto Fiorentino, Firenze, Italy.
    Stocks, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Källman, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Xu, Nannan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Semerikov, Vladimir
    Institute of Plant and Animal Ecology, Ural Division of the Russian Academy of Sciences.
    Vendramin, Giovanni
    CNR, Plant Genetics Institute, Sesto Fiorentino, Firenze, Italy.
    Lascoux, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Clinal variation in allele frequency and gene expression at photoperiodic and circadian genes in Siberian spruce: an example of parallel evolution?Manuskript (preprint) (Annet vitenskapelig)
  • 220.
    Chen, Jun
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Uebbing, Severin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Gyllenstrand, Niclas
    Department of Plant Biology and Forest Genetics, Swedish University of Agriculture Science.
    Lagercrantz, Ulf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Lascoux, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Källman, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Sequencing of the needle transcriptome from Norway spruce (Picea abies Karst L.) reveals lower substitution rates, but similar selective constraints in gymnosperms compared to angiosperms2012Inngår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, s. 589-Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: A detailed knowledge about which genes are expressed in which tissues and at which developmental stage is important for understanding both the function of genes and their evolution. For the vast majority of species, transcriptomes are still largely uncharacterized and even in those where substantial information is available it is often in the form of partially sequenced transcriptomes. With the development of next generation sequencing, a single experiment can now give both a snap-shot of the transcribed part of a species genome and simultaneously estimate levels of gene expression.

    Results: mRNA from actively growing needles of Norway spruce (Picea abies) was sequenced using next generation sequencing technology. In total, close to 70 million fragments with a length of 76 bp were sequenced resulting in 5 Gbp of raw data. A de novo assembly of these reads were, together with publicly available expressed sequence tag (EST) data from Norway spruce, used to create a reference transcriptome. Of the 38,419 PUTs (putative unique transcripts) longer than 150 bp in this reference assembly, 59% show similarity to ESTs from other spruce species and of the remaining PUTs, 3,704 show similarity to protein sequences from other plant species, leaving 4,167 PUTs with limited similarity to currently available plant proteins. By predicting coding frames and comparing not only the Norway spruce PUTs, but also PUTs from the close relatives Picea glauca and Picea sitchensis to both Pinus taeda and Taxus mairei, we obtained estimates of synonymous and non-synonymous divergence among conifer species. In addition, we detected close to 15,000 SNPs of high quality and estimated gene expression difference between samples collected during dark and light conditions.

    Conclusions: Our study yielded a large number of single nucleotide polymorphisms as well as estimates of gene expression on transcriptome scale. In agreement with a recent study we find that the synonymous substitution rate per year (0.6 × 10-09 and 1.1 × 10-09) is an order of magnitude smaller than values reported for angiosperm herbs, but if one takes generation time in to account, most of this difference disappear. The estimates of the non-synonymous over the synonymous divergence (dN/dS ratio) reported here is in general much lower than 1 and only a few genes showed a ratio larger than 1.

    Fulltekst (pdf)
    fulltext
  • 221.
    Chen, Junfeng
    et al.
    Texas A&M Univ, Coll Vet Med, Dept Vet Pathobiol, College Stn, TX 77843 USA..
    Huddleston, John
    Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.;Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA..
    Buckley, Reuben M.
    Univ Adelaide, Sch Biol Sci, Adelaide, SA 5005, Australia..
    Malig, Maika
    Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA..
    Lawhon, Sara D.
    Texas A&M Univ, Coll Vet Med, Dept Vet Pathobiol, College Stn, TX 77843 USA..
    Skow, Loren C.
    Texas A&M Univ, Coll Vet Med, Dept Vet Integrat Biosci, College Stn, TX 77843 USA..
    Lee, Mi Ok
    Texas A&M Univ, Coll Vet Med, Dept Vet Pathobiol, College Stn, TX 77843 USA..
    Eichler, Evan E.
    Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.;Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA..
    Andersson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Texas A&M Univ, Coll Vet Med, Dept Vet Integrat Biosci, College Stn, TX 77843 USA.;Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Womack, James E.
    Texas A&M Univ, Coll Vet Med, Dept Vet Pathobiol, College Stn, TX 77843 USA..
    Bovine NK-lysin: Copy number variation and functional diversification2015Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, nr 52, s. E7223-E7229Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    NK-lysin is an antimicrobial peptide and effector protein in the host innate immune system. It is coded by a single gene in humans and most other mammalian species. In this study, we provide evidence for the existence of four NK-lysin genes in a repetitive region on cattle chromosome 11. The NK2A, NK2B, and NK2C genes are tandemly arrayed as three copies in similar to 30-35-kb segments, located 41.8 kb upstream of NK1. All four genes are functional, albeit with differential tissue expression. NK1, NK2A, and NK2B exhibited the highest expression in intestine Peyer's patch, whereas NK2C was expressed almost exclusively in lung. The four peptide products were synthesized ex vivo, and their antimicrobial effects against both Gram-positive and Gram-negative bacteria were confirmed with a bacteria-killing assay. Transmission electron microcopy indicated that bovine NK-lysins exhibited their antimicrobial activities by lytic action in the cell membranes. In summary, the single NK-lysin gene in other mammals has expanded to a four-member gene family by tandem duplications in cattle; all four genes are transcribed, and the synthetic peptides corresponding to the core regions are biologically active and likely contribute to innate immunity in ruminants.

    Fulltekst (pdf)
    fulltext
  • 222.
    Chen, Lei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Molecular Tools for Biomarker Detection2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The advance of biological research promotes the emerging of new methods and solutions to answer the biological questions. This thesis describes several new molecular tools and their applications for the detection of genomic and proteomic information with extremely high sensitivity and specificity or simplify such detection procedures without compromising the performance.

    In paper I, we described a general method namely super RCA, for highly specific counting of single DNA molecules. Individual products of a range of molecular detection reactions are magnified to Giga-Dalton levels that are easily detected for counting one by one, using methods such as low-magnification microscopy, flow cytometry, or using a mobile phone camera. The sRCA-flow cytometry readout presents extremely high counting precision and the assay’s coefficient of variation can be as low as 0.5%. sRCA-flow cytometry readout can be applied to detect the tumor mutations down to 1/100,000 in the circulating tumor cell-free DNA.

    In paper II, we applied the super RCA method into the in situ sequencing protocol to enhance the amplified mRNA detection tags for better signal-to-noise ratios. The sRCA products co-localize with primary RCA products generated from the gene specific padlock probes and remain as a single individual object in during the sequencing step. The enhanced sRCA products is 100% brighter than regular RCA products and the detection efficiency at least doubled with preserved specificity using sRCA compared to standard RCA.

    In paper III, we described a highly specific and efficient molecular switch mechanism namely RCA reporter. The switch will initiate the rolling circle amplification only in the presence of correct target sequences. The RCA reporter mechanism can be applied to recognize single stranded DNA sequences, mRNA sequences and sequences embedded in the RCA products.

    In paper IV, we established the solid phase Proximity Ligation Assay against the SOX10 protein using poly clonal antibodies. Using this assay, we found elevated SOX10 in serum at high frequency among vitiligo and melanoma patients. While the healthy donors below the threshold.

    Fulltekst (pdf)
    fulltext
    Download (jpg)
    preview image
  • 223.
    Chen, Lei
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala University.
    Björkesten, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Wu, Di
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Mathot, Lucy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    liebs, Sandra
    Haybaeck, Johannes
    Sjöblom, Tobias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Landegren, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Rare Mutation Detection in Blood Plasma Using sRCA Molecule Counting ProbesManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Problems in biology and medicine frequently require the ability to observe, evaluate, andcount even extremely rare macromolecules in biological samples. In particular, rare tumorspecific mutations in plasma provide valuable insights in the course of malignant disease andresponses to therapy, but simpler assay techniques are needed. We describe herein a rapidand exquisitely specific means to recognize and magnify detection signals from individualmolecules to easily recorded levels via a process we call super rolling circle amplification(sRCA). We demonstrate the ability of this technique to enumerate tumor-specific sequencevariants in plasma from cancer patients via flow cytometry at very high efficiency, with specificityadequate to detect single nucleotide mutant sequences among 100,000 copies of thenormal sequence in a 3 hr protocol. And the mutation analysis data generated from patientctDNA samples with our sRCA method are in high accordance with the patients’ primary tumorsequencing data.

  • 224. Chen, Nansheng
    et al.
    Mah, Allan
    Blacque, Oliver E.
    Chu, Jeffrey
    Phgora, Kiran
    Bakhoum, Mathieu W.
    Newbury, C. Rebecca Hunt
    Khattra, Jaswinder
    Chan, Susanna
    Go, Anne
    Efimenko, Evgeni
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institute.
    Johnsen, Robert
    Phirke, Prasad
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institute.
    Swoboda, Peter
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institute.
    Marra, Marco
    Moerman, Donald G.
    Leroux, Michel R.
    Baillie, David L.
    Stein, Lincoln D.
    Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through comparative genomics2006Inngår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 7, nr 12, s. R126-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The recent availability of genome sequences of multiple related Caenorhabditis species has made it possible to identify, using comparative genomics, similarly transcribed genes in Caenorhabditis elegans and its sister species. Taking this approach, we have identified numerous novel ciliary genes in C. elegans, some of which may be orthologs of unidentified human ciliopathy genes. Results: By screening for genes possessing canonical X-box sequences in promoters of three Caenorhabditis species, namely C. elegans, C. briggsae and C. remanei, we identified 93 genes ( including known X-box regulated genes) that encode putative components of ciliated neurons in C. elegans and are subject to the same regulatory control. For many of these genes, restricted anatomical expression in ciliated cells was confirmed, and control of transcription by the ciliogenic DAF-19 RFX transcription factor was demonstrated by comparative transcriptional profiling of different tissue types and of daf-19(+) and daf-19(-) animals. Finally, we demonstrate that the dye-filling defect of dyf-5( mn400) animals, which is indicative of compromised exposure of cilia to the environment, is caused by a nonsense mutation in the serine/threonine protein kinase gene M04C9.5. Conclusion: Our comparative genomics-based predictions may be useful for identifying genes involved in human ciliopathies, including Bardet-Biedl Syndrome ( BBS), since the C. elegans orthologs of known human BBS genes contain X-box motifs and are required for normal dye filling in C. elegans ciliated neurons.

  • 225. Chen, Peng
    et al.
    Jäger, Gunilla
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Zheng, Bo
    Transfer RNA modifications and genes for modifying enzymes in Arabidopsis thaliana2010Inngår i: BMC Plant Biology, ISSN 1471-2229, E-ISSN 1471-2229, Vol. 10, artikkel-id 201Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In all domains of life, transfer RNA (tRNA) molecules contain modified nucleosides. Modifications to tRNAs affect their coding capacity and influence codon-anticodon interactions. Nucleoside modification deficiencies have a diverse range of effects, from decreased virulence in bacteria, neural system disease in human, and gene expression and stress response changes in plants. The purpose of this study was to identify genes involved in tRNA modification in the model plant Arabidopsis thaliana, to understand the function of nucleoside modifications in plant growth and development. Results: In this study, we established a method for analyzing modified nucleosides in tRNAs from the model plant species, Arabidopsis thaliana and hybrid aspen (Populus tremula x tremuloides). 21 modified nucleosides in tRNAs were identified in both species. To identify the genes responsible for the plant tRNA modifications, we performed global analysis of the Arabidopsis genome for candidate genes. Based on the conserved domains of homologs in Sacccharomyces cerevisiae and Escherichia coli, more than 90 genes were predicted to encode tRNA modifying enzymes in the Arabidopsis genome. Transcript accumulation patterns for the genes in Arabidopsis and the phylogenetic distribution of the genes among different plant species were investigated. Transcripts for the majority of the Arabidopsis candidate genes were found to be most abundant in rosette leaves and shoot apices. Whereas most of the tRNA modifying gene families identified in the Arabidopsis genome was found to be present in other plant species, there was a big variation in the number of genes present for each family. Through a loss of function mutagenesis study, we identified five tRNA modification genes (AtTRM10, AtTRM11, AtTRM82, AtKTI12 and AtELP1) responsible for four specific modified nucleosides (m1G, m2G, m7G and ncm5U), respectively (two genes: AtKTI12 and AtELP1 identified for ncm5U modification). The AtTRM11 mutant exhibited an early-flowering phenotype, and the AtELP1 mutant had narrow leaves, reduced root growth, an aberrant silique shape and defects in the generation of secondary shoots. Conclusions: Using a reverse genetics approach, we successfully isolated and identified five tRNA modification genes in Arabidopsis thaliana. We conclude that the method established in this study will facilitate the identification of tRNA modification genes in a wide variety of plant species.

    Fulltekst (pdf)
    fulltext
  • 226.
    Chen, Sa
    Umeå universitet, Teknisk-naturvetenskaplig fakultet, Molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Expression and function of Suppressor of zeste 12 in Drosophila melanogaster2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The development of animals and plants needs a higher order of regulation of gene expression to maintain proper cell state. The mechanisms that control what, when and where a gene should (or should not) be expressed are essential for correct organism development. The Polycomb group (PcG) is a family of genes responsible for maintaining gene silencing and Suppressor of zeste 12 (Su(z)12) is one of the core components in the PcG. The gene is highly conserved in organisms ranging from plants to humans, however, the specific function is not well known. The main tasks of this thesis was to investigate the function of Su(z)12 and its expression at different stages of Drosophila development.

    In polytene chromosomes of larval salivary glands, Su(z)12 binds to about 90 specific euchromatic sites. The binding along the chromosome arms is mostly in interbands, which are the most DNA de-condensed regions. The binding sites of Su(z)12 in polytene chromosomes correlate precisely with those of the Enhancer-of-zeste (E(z)) protein, indicating that Su(z)12 mainly exists within the Polycomb Repressive Complex 2 (PRC2). However, the binding pattern does not overlap well with Histone 3 lysine 27 tri-methylations (H3K27me3), the specific chromatin mark created by PRC2. The Su(z)12 binding to chromatin is dynamically regulated during mitotic and meiotic cell division. The two different Su(z)12 isoforms: Su(z)12-A and Su(z)12-B (resulting from alternative RNA splicing), have very different expression patterns during development. Functional analyses indicate that they also have different functions he Su(z)12-B form is the main mediator of silencing. Furthermore, a neuron specific localization pattern in larval brain and a giant larval phenotype in transgenic lines reveal a potential function of Su(z)12-A in neuron development.  In some aspects the isoforms seem to be able to substitute for each other.

    The histone methyltransferase activity of PRC2 is due to the E(z) protein. However, Su(z)12 is also necessary for H3K27me3 methylation in vivo, and it is thus a core component of PRC2. Clonal over-expression of Su(z)12 in imaginal wing discs results in an increased H3K27me3 activity, indicating that Su(z)12 is a limiting factor for silencing. When PcG function is lost, target genes normally become de-repressed. The segment polarity gene engrailed, encoding a transcription factor, is a target for PRC2 silencing. However, we found that it was not activated when PRC2 function was deleted. We show that the Ultrabithorax protein, encoded by another PcG target gene, also acts as an inhibitor of engrailed and that de-regulation of this gene causes a continued repression of engrailed. The conclusion is that a gene can have several negative regulators working in parallel and that secondary effects have to be taken into consideration, when analyzing effects of mutants.

    PcG silencing affects very many cellular processes and a large quantity of knowledge is gathered on the overall mechanisms of PcG regulation. However, little is known about how individual genes are silenced and how cells “remember” their fate through cell generations.

    Fulltekst (pdf)
    FULLTEXT01
  • 227.
    Chen, Tian-Jiao
    et al.
    Institute of Child and Adolescent Health, School of Public Health, Health Science Center, Peking University, Beijing, China.
    Ji, Cheng-Ye
    Institute of Child and Adolescent Health, School of Public Health, Health Science Center, Peking University, Beijing, China.
    Wang, Shang-Shang
    Institute of Child and Adolescent Health, School of Public Health, Health Science Center, Peking University, Beijing, China.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Chang, Zheng
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Genetic and environmental influences on the relationship between ADHD symptoms and internalizing problems: A Chinese twin study2016Inngår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 171, nr 7, s. 931-937Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Several twin studies have investigated the overlap between attention deficit hyperactivity disorder (ADHD) and externalizing problems; however, limited information is known regarding the genetic and environmental contribution to the overlap between ADHD and internalizing problems. This study examined the genetic and environmental influences on the variation in and covariation between ADHD symptoms and internalizing problems by using the Child Behavior Checklist (CBCL). We investigated 1,316 child and adolescent twins, including 780 monozygotic twins and 536 dizygotic twins, aged 6 years to 18 years from the Chinese Child and Adolescent Twin Registry. ADHD symptoms and internalizing problems were quantified through parent rating by using the Attention Problems Scale and other three scales, which include Anxious/Depressed, Withdrawn, and Somatic Complaints of CBCL. Genetic and environmental susceptibilities common to ADHD symptoms and internalizing problems were examined through bivariate twin modeling. Results showed that genetic factors substantially influenced the ADHD symptoms with a heritability of 72%. Modest genetic influences and substantial shared environmental influences (20-77%) were observed in the three internalizing problem scales. Common genetic and shared environmental influences were essential for the overlap between ADHD and the three internalizing problems respectively. Approximately one-fifth of the genetic variance of ADHD symptoms was shared with anxiety/depression. In conclusion, substantial genetic and shared environmental influences on ADHD symptoms and internalizing problems were observed in Chinese children and adolescents. Our finding supports a common etiology between ADHD and internalizing problems. This finding can also help explain the co-existence of these behavior problems. © 2015 Wiley Periodicals, Inc.

  • 228. Chen, Xinyu
    et al.
    Yuan, Huwei
    Hu, Xiange
    Meng, Jingxiang
    Zhou, Xianqing
    Wang, Xiao-Ru
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. National Engineering Laboratory for Forest Tree Breeding, Key Laboratory of Genetic and Breeding in Forest Trees and Ornamental Plants of Ministry of Education, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, People’s Republic of China.
    Li, Yue
    Variations in electrical impedance and phase angle among seedlings of Pinus densata and parental species in Pinus tabuliformis habitat environment2015Inngår i: Journal of Forestry Research, ISSN 1007-662X, E-ISSN 1993-0607, Vol. 26, nr 3, s. 777-783Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Electrical impedance (EI) and phase angle (PHI) parameters in AC impedance spectroscopy are important electrical parameters in the study of medical pathology. However, little is known about their application in variation and genetic relationship studies of forest trees. In order to test whether impedance parameters could be used in genetic relationship analysis among conifer species, EI and PHI were measured in a seedling experiment test composed of Pinus tabuliformis, Pinus yunnanensis, and Pinus densata in a habitat of Pinus tabuliformis. The results showed that variations in both EI and PHI among species were significant in different electric frequencies, and the EI and PHI values measured in the two populations of P. densata were between the two parental species, P. yunnanensis and P. tabuliformis. These results show that these two impedance parameters could reflect the genetic relationship among pine species. This was the first time using the two AC impedance spectroscopy parameters to test the genetic relationship analysis between tree species, and would be a hopeful novel reference methodology for future studies in evolution and genetic variation of tree species.

  • 229.
    Cheng, George
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Uncovering the genetic organisation of Claroideoglomus candidum2019Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
    Abstract [en]

    Arbuscular mycorrhizal (AM) fungi are hypothesized to have been key players in facilitating thetransition from aquatic to terrestrial plants and continue to benefit plants through their symbioticassociation after 450 million years. These fungi form mycelia that can contain hundreds of nucleiwithin one aseptate cytoplasm, which leads to the ongoing debate on whether thesemultinucleated fungi are homokaryotic or heterokaryotic. Not only is there evidence to supportthe hypothesis of the nuclei as genetically identical, but also the other hypothesis of divergentnuclei within a single strain. There has been no evidence of sexual reproduction, howeverspecialized genomic regions specific to meiosis and a putative mating-type (MAT) locus haverecently been identified and may help answer the ongoing debate between homokaryosis andheterokaryosis.

    In this study I applied de novo genome assembly and annotation of 24 individual nuclei from asingle spore of Claroideoglomus candidum. The full length of the de novo genome assembly was87.6 Mb with 17,542 genes. Estimated polymorphism between the nuclei was very low. Iidentified the MAT locus in C. candidum, using a previously sequenced MAT locus fromanother congeneric species. Only one of the MAT locus alleles was found in the examined spore.The evidence points towards homokaryosis as the genetic organization of Claroideoglomuscandidum.

    Fulltekst (pdf)
    fulltext
  • 230.
    Cherif, E.
    et al.
    Ctr IRD, UMR DIADE, IRD CIRAD Palm Grp F2F, 911 Ave Agropolis, F-34394 Montpellier, France.;Univ Tunis El Manar, Fac Sci Tunis, Lab Genet Mol Immunol & Biotechnol, El Manar, Tunisia..
    Zehdi-Azouzi, S.
    Univ Tunis El Manar, Fac Sci Tunis, Lab Genet Mol Immunol & Biotechnol, El Manar, Tunisia..
    Crabos, A.
    Ctr IRD, UMR DIADE, IRD CIRAD Palm Grp F2F, 911 Ave Agropolis, F-34394 Montpellier, France..
    Castillo, K.
    Ctr IRD, UMR DIADE, IRD CIRAD Palm Grp F2F, 911 Ave Agropolis, F-34394 Montpellier, France..
    Chabrillange, N.
    Ctr IRD, UMR DIADE, IRD CIRAD Palm Grp F2F, 911 Ave Agropolis, F-34394 Montpellier, France..
    Pintaud, J. -C
    Salhi-Hannachi, A.
    Univ Tunis El Manar, Fac Sci Tunis, Lab Genet Mol Immunol & Biotechnol, El Manar, Tunisia..
    Glemin, Sylvain
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution. Unite Mixte Rech 5554 Univ Montpellier CNRS IRD E, Inst Sci Evolut Montpellier, Montpellier, France..
    Aberlenc-Bertossi, F.
    Ctr IRD, UMR DIADE, IRD CIRAD Palm Grp F2F, 911 Ave Agropolis, F-34394 Montpellier, France..
    Evolution of sex chromosomes prior to speciation in the dioecious Phoenix species2016Inngår i: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 29, nr 8, s. 1513-1522Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Understanding the driving forces and molecular processes underlying dioecy and sex chromosome evolution, leading from hermaphroditism to the occurrence of male and female individuals, is of considerable interest in fundamental and applied research. The genus Phoenix, belonging to the Arecaceae family, consists uniquely of dioecious species. Phylogenetic data suggest that the genus Phoenix has diverged from a hermaphroditic ancestor which is also shared with its closest relatives. We have investigated the cessation of recombination in the sex-determination region within the genus Phoenix as a whole by extending the analysis of P.dactylifera SSR sex-related loci to eight other species within the genus. Phylogenetic analysis of a date palm sex-linked PdMYB1 gene in these species has revealed that sex-linked alleles have not clustered in a species-dependent way but rather in X and Y-allele clusters. Our data show that sex chromosomes evolved from a common autosomal origin before the diversification of the extant dioecious species.

  • 231.
    Christmas, Matthew J
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wallberg, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bunikis, Ignas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Olsson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wallerman, Ola
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Webster, Matthew T
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Chromosomal inversions associated with environmental adaptation in honeybees2019Inngår i: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 28, nr 6, s. 1358-1374Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chromosomal inversions can facilitate local adaptation in the presence of gene flow by suppressing recombination between well-adapted native haplotypes and poorly adapted migrant haplotypes. East African mountain populations of the honeybee Apis mellifera are highly divergent from neighbouring lowland populations at two extended regions in the genome, despite high similarity in the rest of the genome, suggesting that these genomic regions harbour inversions governing local adaptation. Here, we utilize a new highly contiguous assembly of the honeybee genome to characterize these regions. Using whole-genome sequencing data from 55 highland and lowland bees, we find that the highland haplotypes at both regions are present at high frequencies in three independent highland populations but extremely rare elsewhere. The boundaries of both divergent regions are characterized by regions of high homology with each other positioned in opposite orientations and contain highly repetitive, long inverted repeats with homology to transposable elements. These regions are likely to represent inversion breakpoints that participate in nonallelic homologous recombination. Using long-read data, we confirm that the lowland samples are contiguous across breakpoint regions. We do not find evidence for disruption of functional sequence by these breakpoints, which suggests that the inversions are likely maintained due to their allelic content conferring local adaptation in highland environments. Finally, we identify a third divergent genomic region, which contains highly divergent segregating haplotypes that also may contain inversion variants under selection. The results add to a growing body of evidence indicating the importance of chromosomal inversions in local adaptation.

  • 232.
    Christmas, Matthew
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Smith, Nicholas M. A.
    Univ Sydney, Behav & Genet Social Insects Lab, Ecol & Evolut, Sydney, NSW, Australia.
    Oldroyd, Benjamin P.
    Univ Sydney, Behav & Genet Social Insects Lab, Ecol & Evolut, Sydney, NSW, Australia.
    Webster, Matthew Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Social Parasitism in the Honeybee (Apis mellifera) Is Not Controlled by a Single SNP2019Inngår i: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 36, nr 8, s. 1764-1767Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Cape bee (Apis mellifera capensis) is a subspecies of the honeybee, in which workers commonly lay diploid unfertilized eggs via a process known as thelytoky. A recent study aimed to map the genetic basis of this trait in the progeny of a single capensis queen where workers laid either diploid (thelytokous) or haploid (arrhenotokous) eggs. A nonsynonymous single nucleotide polymorphism (SNP) in a gene of unknown function was reported to be strongly associated with thelytoky in this colony. Here, we analyze genome sequences from a global sample of A. mellifera and identify populations where the proposed thelytoky allele at this SNP is common but thelytoky is absent. We also analyze genome sequences of three capensis queens produced by thelytoky and find that, contrary to predictions, they do not carry the proposed thelytoky allele. The proposed SNP is therefore neither sufficient nor required to produce thelytoky in A. mellifera.

  • 233.
    Christophersen, Ingrid E.
    et al.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Rud, Norway..
    Rienstra, Michiel
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Roselli, Carolina
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Yin, Xiaoyan
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Geelhoed, Bastiaan
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Barnard, John
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Lin, Honghuang
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Arking, Dan E.
    Johns Hopkins Univ Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Albert, Christine M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Chaffin, Mark
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Tucker, Nathan R.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Li, Molong
    Klarin, Derek
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Bihlmeyer, Nathan A.
    Johns Hopkins Univ Sch Med, McKusick Nathans Inst Genet Med, Predoctoral Training Program Human Genet, Baltimore, MD USA..
    Low, Siew-Kee
    RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan..
    Weeke, Peter E.
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA.;Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Copenhagen, Denmark..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Smith, J. Gustav
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Lund Univ, Clin Sci, Molecular Epidemiol & Cardiol, Lund, Sweden..
    Brody, Jennifer A.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Niemeijer, Maartje N.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Huffman, Jennifer
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Seppala, Ilkka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Malik, Rainer
    Klinikum Univ Munchen, Inst Stroke & Dementia Res, Ludwig Maximilians Univ, Munich, Germany..
    Horimoto, Andrea R. V. R.
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil..
    Perez, Marco
    Stanford Univ, Dept Cardiovasc Med, Stanford, CA 94305 USA..
    Sinisalo, Juha
    Univ Helsinki, Cent Hosp, Heart & Lung Ctr HUS, Helsinki, Finland..
    Aeschbacher, Stefanie
    Univ Basel Hosp, Dept Med, Basel, Switzerland.;Cardiovasc Res Inst Basel, Basel, Switzerland..
    Theriault, Sebastien
    Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Yao, Jie
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Radmanesh, Farid
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Weiss, Stefan
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med, Interfac Inst Genet & Funct Gen, Greifswald, Germany.;Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany..
    Teumer, Alexander
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Choi, Seung Hoan
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Weng, Lu-Chen
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Clauss, Sebastian
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Deo, Rajat
    Univ Penn, Perelman Sch Med, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA..
    Rader, Daniel J.
    Univ Penn, Perelman Sch Med, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA..
    Shah, Svati H.
    Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA..
    Sun, Albert
    Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA..
    Hopewell, Jemma C.
    Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England..
    Debette, Stephanie
    Bordeaux Populat Hlth Ctr, INSERM U1219, Bordeaux, France.;Univ Bordeaux, Bordeaux, France.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA..
    Chauhan, Ganesh
    Bordeaux Populat Hlth Ctr, INSERM U1219, Bordeaux, France.;Univ Bordeaux, Bordeaux, France..
    Yang, Qiong
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Worrall, Bradford B.
    Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA.;Univ Virginia Hlth Syst, Dept Publ Hlth Sci, Charlottesville, VA USA..
    Pare, Guillaume
    Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Kamatani, Yoichiro
    RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan..
    Hagemeijer, Yanick P.
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Verweij, Niek
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Siland, Joylene E.
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Kubo, Michiaki
    RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan..
    Smith, Jonathan D.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Van Wagoner, David R.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Perz, Siegfried
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Washington, DC USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Magnani, Jared W.
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA..
    Harris, Tamara B.
    Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA..
    Launer, Lenore J.
    Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA..
    Shoemaker, M. Benjamin
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Padmanabhan, Sandosh
    Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Haessler, Jeffrey
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA..
    Bartz, Traci M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Biostat, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Waldenberger, Melanie
    DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Lichtner, Peter
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, Neuherberg, Germany..
    Arendt, Marina
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Krieger, Jose E.
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil..
    Kahonen, Mika
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland..
    Risch, Lorenz
    Univ Bern, Univ Inst Clin Chem, Bern, Switzerland.;Labormed Zentrum Dr Risch, Schaan, Liechtenstein..
    Mansur, Alfredo J.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil..
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Smith, Blair H.
    Univ Dundee, Div Populat Hlth Sci, Dundee, Scotland..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Scott, Stuart A.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Bottinger, Erwin B.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA..
    Hernesniemi, Jussi
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere, Finland..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Wong, Jorge A.
    McMaster Univ, Div Cardiol Hamilton Hlth Sci, Hamilton, ON, Canada..
    Huang, Jie
    Boston VA Res Inst Inc, Boston, MA USA..
    Eskola, Markku
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere, Finland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany..
    Chen, Lin Y.
    Univ Minnesota, Dept Med, Med Sch, Cardiovasc Div, Box 736 UMHC, Minneapolis, MN 55455 USA..
    Chen, Yii-Der Ida
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Sandhu, Roopinder K.
    Univ Alberta, Div Cardiol, Edmonton, AB, Canada..
    Li, Man
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.;Univ Utah, Sch Med, Div Nephrol & Hypertens, Internal Med, Salt Lake City, UT USA..
    Boerwinkle, Eric
    Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Eisele, Lewin
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Rost, Natalia
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Acute Stroke Serv, Boston, MA 02114 USA..
    Anderson, Christopher D.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Taylor, Kent D.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Porteous, David
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    Hocking, Lynne J.
    Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen, Scotland..
    Vlachopoulou, Efthymia
    Univ Helsinki, Medicum, Transplantat Lab, Helsinki, Finland..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Nikus, Kjell
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere, Finland..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden..
    Heeringa, Jan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Denny, Joshua C.
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Kriebel, Jennifer
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Darbar, Dawood
    Univ Illinois, Dept Med & Pharmacol, Chicago, IL USA..
    Newton-Cheh, Christopher
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Shaffer, Christian
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Macfarlane, Peter W.
    Univ Glasgow, Coll Med Vet & Sci, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Heilmann-Heimbach, Stefanie
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Res Ctr, Dept Gen, Bonn, Germany..
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Huang, Paul L.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Sotoodehnia, Nona
    Univ Washington, Cardiovasc Hlth Res Unit, Washington, DC USA..
    Soliman, Elsayed Z.
    Wake Forest Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol & Internal Med, Rotterdam, Netherlands..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med, Interfac Inst Genet & Funct Gen, Greifswald, Germany.;Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany..
    Joeckel, Karl-Heinz
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Sinner, Moritz F.
    Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Lin, Henry J.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Guo, Xiuqing
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Dichgans, Martin
    Klinikum Univ Munchen, Inst Stroke & Dementia Res, Ludwig Maximilians Univ, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany.;German Ctr Neurodegenerat Dis DZNE, Munich, Germany..
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Kooperberg, Charles
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA..
    Melander, Olle
    Lund Univ, Clin Sci, Dept Internal Med, Malmo, Sweden..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Laurikka, Jari
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardio Thorac Surg, Tampere, Finland..
    Conen, David
    Univ Basel Hosp, Dept Med, Basel, Switzerland.;Cardiovasc Res Inst Basel, Basel, Switzerland..
    Rosand, Jonathan
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    van der Harst, Pim
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Lokki, Marja-Liisa
    Univ Helsinki, Medicum, Transplantat Lab, Helsinki, Finland..
    Kathiresan, Sekar
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Pereira, Alexandre
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil.;Harvard Med Sch, Dept Genet, Boston, MA USA..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, LABioMed, Dept Med, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Maerz, Winfried
    Med Univ Graz, Inst Clin Med, Graz, Austria.;Med Univ Graz, Chem Lab Diagnost, Graz, Austria.;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany.;Synlab Holding Deutschland GmbH, Synlab Acad, Augsburg, Germany..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Stricker, Bruno H.
    Erasmus MC, Dept Epidemiol & Internal Med, Rotterdam, Netherlands.;Inspectorate Hlth Care, Utrecht, Netherlands..
    Chung, Mina K.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Felix, Stephan B.
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Alonso, Alvaro
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA..
    Roden, Dan M.
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Kaeaeb, Stefan
    Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Chasman, Daniel I.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA..
    Heckbert, Susan R.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Washington, DC USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA..
    Benjamin, Emelia J.
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA.;Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA..
    Tanaka, Toshihiro
    RIKEN, Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan.;Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo, Japan..
    Lunetta, Kathryn L.
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA..
    Lubitz, Steven A.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA..
    Ellinor, Patrick T.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA..
    Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation2017Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, nr 6, s. 946-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death(1,2). Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups(3-7). To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery(8).

  • 234.
    Chylenski, Maciej
    et al.
    Adam Mickiewicz Univ, Fac Hist, Inst Archaeol, Umultowska 89D, PL-61614 Poznan, Poland..
    Juras, Anna
    Adam Mickiewicz Univ, Fac Biol, Inst Anthropol, Dept Human Evolutionary Biol, Umultowska 89, PL-61614 Poznan, Poland..
    Ehler, Edvard
    Adam Mickiewicz Univ, Fac Biol, Inst Anthropol, Dept Human Evolutionary Biol, Umultowska 89, PL-61614 Poznan, Poland.;Charles Univ Prague, Fac Educ, Dept Biol & Environm Studies, Magdaleny Rettigove 4, Prague 11639, Czech Republic..
    Malmström, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Piontek, Janusz
    Adam Mickiewicz Univ, Fac Biol, Inst Anthropol, Dept Human Evolutionary Biol, Umultowska 89, PL-61614 Poznan, Poland..
    Jakobsson, Mattias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Marciniak, Arkadiusz
    Adam Mickiewicz Univ, Fac Hist, Inst Archaeol, Umultowska 89D, PL-61614 Poznan, Poland..
    Dabert, Miroslawa
    Adam Mickiewicz Univ, Fac Biol, Mol Biol Techn Lab, Umultowska 89, PL-61614 Poznan, Poland..
    Late Danubian mitochondrial genomes shed light into the Neolithisation of Central Europe in the 5th millennium BC2017Inngår i: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 17, artikkel-id 80Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Recent aDNA studies are progressively focusing on various Neolithic and Hunter-Gatherer (HG) populations, providing arguments in favor of major migrations accompanying European Neolithisation. The major focus was so far on the Linear Pottery Culture (LBK), which introduced the Neolithic way of life in Central Europe in the second half of 6th millennium BC. It is widely agreed that people of this culture were genetically different from local HGs and no genetic exchange is seen between the two groups. From the other hand some degree of resurgence of HGs genetic component is seen in late Neolithic groups belonging to the complex of the Funnel Beaker Cultures (TRB). Less attention is brought to various middle Neolithic cultures belonging to Late Danubian sequence which chronologically fall in between those two abovementioned groups. We suspected that genetic influx from HG to farming communities might have happened in Late Danubian cultures since archaeologists see extensive contacts between those two communities. Results: Here we address this issue by presenting 5 complete mitochondrial genomes of various late Danubian individuals from modern-day Poland and combining it with available published data. Our data show that Late Danubian cultures are maternally closely related to Funnel Beaker groups instead of culturally similar LBK. Conclusions: We assume that it is an effect of the presence of individuals belonging to U5 haplogroup both in Late Danubians and the TRB. The U5 haplogroup is thought to be a typical for HGs of Europe and therefore we argue that it is an additional evidence of genetic exchange between farming and HG groups taking place at least as far back as in middle Neolithic, in the Late Danubian communities.

    Fulltekst (pdf)
    fulltext
  • 235.
    Clement, Yves
    et al.
    Montpellier SupAgro, UMR AGAP, Montpellier, France.;Univ Montpellier, CNRS IRD EPHE, UMR ISEM 5554, Montpellier, France.;PSL Res Univ, Ecole Normale Super, CNRS, IBENS,INSERM, Paris, France..
    Sarah, Gautier
    INRA, UMR AGAP, Montpellier, France.;SouthGreen Platform, Montpellier, France..
    Holtz, Yan
    Montpellier SupAgro, UMR AGAP, Montpellier, France..
    Homa, Felix
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab. SouthGreen Platform, Montpellier, France..
    Pointet, Stephanie
    SouthGreen Platform, Montpellier, France.;CIRAD, UMR AGAP, Montpellier, France.;ALCEDIAG CNRS Sys2Diag FRE3690, Biol Complex Syst Modelling & Engn Diag, Montpellier, France..
    Contreras, Sandy
    SouthGreen Platform, Montpellier, France.;GenoScreen, Lille, France..
    Nabholz, Benoit
    Univ Montpellier, CNRS IRD EPHE, UMR ISEM 5554, Montpellier, France..
    Sabot, Francois
    SouthGreen Platform, Montpellier, France.;IRD, UMR DIADE, Montpellier, France..
    Saune, Laure
    INRA, CBGP UMR1062, Montferrier Sur Lez, France..
    Ardisson, Morgane
    INRA, UMR AGAP, Montpellier, France..
    Bacilieri, Roberto
    INRA, UMR AGAP, Montpellier, France..
    Besnard, Guillaume
    Univ Toulouse III, CNRS ENSFEA IRD, UMR EDB 5174, Toulouse, France..
    Berger, Angelique
    CIRAD, UMR AGAP, Montpellier, France..
    Cardi, Celine
    CIRAD, UMR AGAP, Montpellier, France..
    De Bellis, Fabien
    CIRAD, UMR AGAP, Montpellier, France..
    Fouet, Olivier
    CIRAD, UMR AGAP, Montpellier, France..
    Jourda, Cyril
    CIRAD, UMR AGAP, Montpellier, France.;CIRAD, UMR PVBMT, St Pierre, Reunion, France..
    Khadari, Bouchaib
    INRA, UMR AGAP, Montpellier, France..
    Lanaud, Claire
    CIRAD, UMR AGAP, Montpellier, France..
    Leroy, Thierry
    CIRAD, UMR AGAP, Montpellier, France..
    Pot, David
    Sauvage, Christopher
    INRA, GAFL UR1052, Montfavet, France..
    Scarcelli, Nora
    IRD, UMR DIADE, Montpellier, France..
    Tregear, James
    IRD, UMR DIADE, Montpellier, France..
    Vigouroux, Yves
    IRD, UMR DIADE, Montpellier, France..
    Yahiaoui, Nabila
    CIRAD, UMR AGAP, Montpellier, France..
    Ruiz, Manuel
    SouthGreen Platform, Montpellier, France.;CIRAD, UMR AGAP, Montpellier, France..
    Santoni, Sylvain
    INRA, UMR AGAP, Montpellier, France..
    Labouisse, Jean-Pierre
    CIRAD, UMR AGAP, Montpellier, France..
    Pham, Jean-Louis
    IRD, UMR DIADE, Montpellier, France..
    David, Jacques
    Montpellier SupAgro, UMR AGAP, Montpellier, France..
    Glemin, Sylvain
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution. Univ Montpellier.
    Evolutionary forces affecting synonymous variations in plant genomes2017Inngår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, nr 5, artikkel-id e1006799Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Base composition is highly variable among and within plant genomes, especially at third codon positions, ranging from GC-poor and homogeneous species to GC-rich and highly heterogeneous ones (particularly Monocots). Consequently, synonymous codon usage is biased in most species, even when base composition is relatively homogeneous. The causes of these variations are still under debate, with three main forces being possibly involved: mutational bias, selection and GC-biased gene conversion (gBGC). So far, both selection and gBGC have been detected in some species but how their relative strength varies among and within species remains unclear. Population genetics approaches allow to jointly estimating the intensity of selection, gBGC and mutational bias. We extended a recently developed method and applied it to a large population genomic dataset based on transcriptome sequencing of 11 angiosperm species spread across the phylogeny. We found that at synonymous positions, base composition is far from mutation-drift equilibrium in most genomes and that gBGC is a widespread and stronger process than selection. gBGC could strongly contribute to base composition variation among plant species, implying that it should be taken into account in plant genome analyses, especially for GC-rich ones.

    Fulltekst (pdf)
    fulltext
  • 236.
    Clergeot, Pierre-Henri
    et al.
    Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, SE-75007 Uppsala, Sweden.
    Rode, Nicolas O.
    Univ Montpellier, Montpellier SupAgro, IRD, CBGP,INRA,Ctr Cooperat Int Rech Agron Dev CIRAD, F-34988 Montpellier, France.
    Glemin, Sylvain
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution. Univ Rennes, CNRS, ECOBIO Ecosyst Biodiversite Evolut UMR 6553, F-35000 Rennes, France.
    Durling, Mikael Brandstrom
    Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, SE-75007 Uppsala, Sweden.
    Ihrmark, Katarina
    Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, SE-75007 Uppsala, Sweden.
    Olson, Ake
    Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, SE-75007 Uppsala, Sweden.
    Estimating the Fitness Effect of Deleterious Mutations During the Two Phases of the Life Cycle: A New Method Applied to the Root-Rot Fungus Heterobasidion parviporum2019Inngår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 211, nr 3, s. 963-976Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many eukaryote species, including taxa such as fungi or algae, have a lifecycle with substantial haploid and diploid phases. A recent theoretical model predicts that such haploid-diploid lifecycles are stable over long evolutionary time scales when segregating deleterious mutations have stronger effects in homozygous diploids than in haploids and when they are partially recessive in heterozygous diploids. The model predicts that effective dominance-a measure that accounts for these two effects-should be close to 0.5 in these species. It also predicts that diploids should have higher fitness than haploids on average. However, an appropriate statistical framework to conjointly investigate these predictions is currently lacking. In this study, we derive a new quantitative genetic model to test these predictions using fitness data of two haploid parents and their diploid offspring, and genome-wide genetic distance between haploid parents. We apply this model to the root-rot basidiomycete fungus Heterobasidion parviporum-a species where the heterokaryotic (equivalent to the diploid) phase is longer than the homokaryotic (haploid) phase. We measured two fitness-related traits (mycelium growth rate and the ability to degrade wood) in both homokaryons and heterokaryons, and we used whole-genome sequencing to estimate nuclear genetic distance between parents. Possibly due to a lack of power, we did not find that deleterious mutations were recessive or more deleterious when expressed during the heterokaryotic phase. Using this model to compare effective dominance among haploid-diploid species where the relative importance of the two phases varies should help better understand the evolution of haploid-diploid life cycles.

  • 237. Collins, Emily
    et al.
    Sullivan, Alexis R.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Gailing, Oliver
    Limited effective gene flow between two interfertile red oak species2015Inngår i: Trees, ISSN 0931-1890, E-ISSN 1432-2285, Vol. 29, nr 4, s. 1135-1148Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Highly elevated differentiation in different life stages between two interfertile oak species at a CONSTANS -like gene suggests a role of this gene in pre-zygotic isolation and adaptive divergence between species. Genome-wide differentiation patterns among oak species suggest that divergent selection can maintain species-specific adaptations and morphological integrity by reducing effective interspecific gene flow. While there is evidence for both pre- and post-zygotic isolation mechanisms in oaks (e.g., differences in flowering time, selection against hybrids), these mechanisms are rarely studied at each life stage from acorns to adult trees within the same forest. To assess the reproductive isolation mechanisms between two ecologically divergent species, we (1) quantified the number of hybrids in different life stages in Quercus rubra and Quercus ellipsoidalis, two interfertile red oaks with different adaptations to drought, and (2) assessed the timing of bud burst in both natural populations and in a seedling common garden trial. The low number of hybrids in all life stages suggested pre-zygotic isolation between species or selection in very early life stages that have not been sampled (e.g., early seed abortion). Significant differences in bud burst were found in two consecutive years between species in a common garden seedling trial but not in natural populations of the same provenance. In addition, we found evidence for divergent selection on several gene loci between species in each life stage. In particular, an SSR repeat located within the coding sequence of a CONSTANS-like gene, a locus involved in the photoperiodic regulation of flowering time and development, showed very high interspecific differentiation between species in all life stages (mean F (ST) = 0.83), compared to the average neutral differentiation of 3.7 %.

  • 238.
    Connallon, Tim
    et al.
    Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia;Monash Univ, Ctr Geometr Biol, Clayton, Vic 3800, Australia.
    Olito, Colin
    Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia;Monash Univ, Ctr Geometr Biol, Clayton, Vic 3800, Australia;Lund Univ, Sect Evolutionary Ecol, Dept Biol, S-22362 Lund, Sweden.
    Dutoit, Ludovic
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi. Univ Otago, Dept Zool, Dunedin 9054, New Zealand.
    Papoli, Homa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Ruzicka, Filip
    UCL, Res Dept Genet Evolut & Environm, London WC1E 6BT, England.
    Yong, Lengxob
    Univ Exeter, Ctr Ecol & Conservat, Penryn TR10 9FE, England.
    Local adaptation and the evolution of inversions on sex chromosomes and autosomes2018Inngår i: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 373, nr 1757, artikkel-id 20170423Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Spatially varying selection with gene flow can favour the evolution of inversions that bind locally adapted alleles together, facilitate local adaptation and ultimately drive genomic divergence between species. Several studies have shown that the rates of spread and establishment of new inversions capturing locally adaptive alleles depend on a suite of evolutionary factors, including the strength of selection for local adaptation, rates of gene flow and recombination, and the deleterious mutation load carried by inversions. Because the balance of these factors is expected to differ between X (or Z) chromosomes and autosomes, opportunities for inversion evolution are likely to systematically differ between these genomic regions, though such scenarios have not been formally modelled. Here, we consider the evolutionary dynamics of X-linked and autosomal inversions in populations evolving at a balance between migration and local selection. We identify three factors that lead to asymmetric rates of X-linked and autosome inversion establishment: (1) sex-biased migration, (2) dominance of locally adapted alleles and (3) chromosome-specific deleterious mutation loads. This theory predicts an elevated rate of fixation, and depressed opportunities for polymorphism, for X-linked inversions. Our survey of data on the genomic distribution of polymorphic and fixed inversions supports both theoretical predictions. This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.

  • 239. Corander, Jukka
    et al.
    Gyllenberg, Mats
    Koski, Timo
    KTH, Skolan för teknikvetenskap (SCI), Matematik (Inst.), Matematisk statistik.
    Learning Genetic Population Structures Using Minimization of Stochastic Complexity2010Inngår i: Entropy, ISSN 1099-4300, E-ISSN 1099-4300, Vol. 12, nr 5, s. 1102-1124Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Considerable research efforts have been devoted to probabilistic modeling of genetic population structures within the past decade. In particular, a wide spectrum of Bayesian models have been proposed for unlinked molecular marker data from diploid organisms. Here we derive a theoretical framework for learning genetic population structure of a haploid organism from bi-allelic markers for which potential patterns of dependence are a priori unknown and to be explicitly incorporated in the model. Our framework is based on the principle of minimizing stochastic complexity of an unsupervised classification under tree augmented factorization of the predictive data distribution. We discuss a fast implementation of the learning framework using deterministic algorithms.

  • 240.
    Corcoran, Pádraic
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Neurospora tetrasperma from Natural Populations: Toward the Population Genomics of a Model Fungus2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The study of DNA sequence variation is a powerful approach to study genome evolution, and to reconstruct evolutionary histories of species. In this thesis, I have studied genetic variation in the fungus Neurospora tetrasperma and other closely related Neurospora species. I have focused on N. tetrasperma in my research because it has large regions of suppressed recombination on its mating-type chromosomes, had undergone a recent change in reproductive mode and is composed of multiple reproductively isolated lineages. Using DNA sequence data from a large sample set representing multiple species of Neurospora I estimated that N. tetrasperma evolved ~1 million years ago and that it is composed of at least 10 lineages. My analysis of the type of asexual spores produced using newly described N. tetrasperma populations in Britain revealed that lineages differ considerably in life history characteristics that may have consequences for their evolution. A comparative genomic analysis using three genomes of N. tetrasperma and the genome of N. crassa revealed that the mat a chromosomes in the lineages examine have been introgressed from other Neurospora species and that this introgression has reduced levels of molecular degeneration on the mating-type chromosomes. Finally, I generated a population genomic dataset composed of 92 N. tetrasperma genomes and two genomes of other Neurospora species. Analysis of these genomes revealed that all strains of N. tetrasperma have large regions of suppressed recombination on their mating-type chromosomes ranging from 69-84% of the chromosome and that the extent of divergence between mating-type chromosomes within lineages varies greatly (from 1.3 to 3.2%). I concluded that the source of this great divergence mating-type chromosome is large-scale introgression from other Neurospora species, and that these introgressed tracts have become fixed within N. tetrasperma lineages. I also discovered that genes within non-recombining introgressed regions of the mating-type chromosome have severely reduced levels of genetic variation as compared to the autosomes, and exhibit signatures of reduced molecular degeneration. My analysis of variation in coding regions revealed that positive selection on the introgressed regions has resulted in the removal of deleterious mutations and is responsible for the reductions in molecular degeneration observed.

    Fulltekst (pdf)
    fulltext
    Download (jpg)
    presentationsbild
  • 241.
    Corcoran, Pádraic
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Chen, Fen
    BGI, Hong Kong.
    Lascoux, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Ni, Peixang
    BGI, Hong Kong.
    Johanesson, Hanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Adaptive introgression slows down molecular degeneration of the mating-type chromosome in Neurospora tetraspermaManuskript (preprint) (Annet vitenskapelig)
  • 242.
    Cornille, Amandine
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik.
    Salcedo, A.
    Univ Toronto, Dept Ecol & Evolutionary Biol, 25 Willcocks St, Toronto, ON M6R 1M3, Canada..
    Kryvokhyzha, Dmytro
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Glemin, Sylvain
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Holm, Karl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Wright, S. I.
    Univ Toronto, Dept Ecol & Evolutionary Biol, 25 Willcocks St, Toronto, ON M6R 1M3, Canada..
    Lascoux, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Genomic signature of successful colonization of Eurasia by the allopolyploid shepherd's purse (Capsella bursa-pastoris)2016Inngår i: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 25, nr 2, s. 616-629Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 243.
    Cortes, Andres J.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Waeber, S.
    Lexer, C.
    Sedlacek, J.
    Wheeler, J. A.
    van Kleunen, M.
    Bossdorf, O.
    Hoch, G.
    Rixen, C.
    Wipf, S.
    Karrenberg, Sophie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Small-scale patterns in snowmelt timing affect gene flow and the distribution of genetic diversity in the alpine dwarf shrub Salix herbacea2014Inngår i: Heredity, ISSN 0018-067X, E-ISSN 1365-2540, Vol. 113, nr 3, s. 233-239Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 244.
    Cortobius Fredriksson, Moa
    Södertörns högskola, Institutionen för livsvetenskaper.
    ProBenefit: Implementing the Convention on Biological Diversity in the Ecuadorian Amazon2009Independent thesis Basic level (degree of Bachelor), 15 poäng / 22,5 hpOppgave
    Abstract [en]

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

    Fulltekst (pdf)
    FULLTEXT01
  • 245. Cossu, Rosa Maria
    et al.
    Casola, Claudio
    Giacomello, Stefania
    Vidalis, Amaryllis
    Scofield, Douglas G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Zuccolo, Andrea
    LTR Retrotransposons Show Low Levels of Unequal Recombination and High Rates of Intraelement Gene Conversion in Large Plant Genomes2017Inngår i: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 9, nr 12, s. 3449-3462Artikkel i tidsskrift (Fagfellevurdert)
  • 246. Cossu, Rosa Maria
    et al.
    Casola, Claudio
    Giacomello, Stefania
    Vidalis, Amaryllis
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Section of Population Epigenetics and Epigenomics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Freising, Germany.
    Scofield, Douglas G.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Department of Ecology and Genetics: Evolutionary Biology, Uppsala University, Sweden; Uppsala Multidisciplinary Center for Advanced Computational Science, Uppsala University, Sweden.
    Zuccolo, Andrea
    LTR Retrotransposons Show Low Levels of Unequal Recombination and High Rates of Intraelement Gene Conversion in Large Plant Genomes2017Inngår i: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 9, nr 12, s. 3449-3462Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

    Fulltekst (pdf)
    fulltext
  • 247. 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, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, 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-22016Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, nr 30, s. 47221-47231Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 248. Cotton, James A.
    et al.
    Berriman, Matthew
    Dalén, Love
    Naturhistoriska riksmuseet, Enheten för bioinformatik och genetik.
    Barnes, Ian
    Eradication genomics-lessons for parasite control2018Inngår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 361, nr 6398, s. 130-131Artikkel i tidsskrift (Fagfellevurdert)
  • 249.
    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 universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Larsson, Jan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Mannervik, Mattias
    Stockholm University, Wenner-Gren Institute, Developmental Biology, Arrhenius laboratories E3, Stockholm SE-10691, Sweden.
    Gene regulation by the lysine demethylase KDM4A in Drosophila2013Inngår i: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 737, nr 2, s. 453-463Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 250.
    Crooks, Lucy
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Nettelblad, Carl
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för teknisk databehandling. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Tillämpad beräkningsvetenskap.
    Carlborg, Örjan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    An improved method for estimating chromosomal line origin in QTL analysis of crosses between outbred lines2011Inngår i: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 1, s. 57-64Artikkel i tidsskrift (Fagfellevurdert)
2345678 201 - 250 of 1525
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf