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Sökning: L773:2160 1836 OR L773:2160 1836

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  • [1]234567...8Nästa
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1.
  • Apuli, Rami-Petteri, et al. (författare)
  • Inferring the Genomic Landscape of Recombination Rate Variation in European Aspen (Populus tremula)
  • 2020
  • Ingår i: G3. - : GENETICS SOCIETY AMERICA. - 2160-1836 .- 2160-1836. ; 10:1, s. 299-309
  • Tidskriftsartikel (refereegranskat)abstract
    • The rate of meiotic recombination is one of the central factors determining genome-wide levels of linkage disequilibrium which has important consequences for the efficiency of natural selection and for the dissection of quantitative traits. Here we present a new, high-resolution linkage map for Populus tremula that we use to anchor approximately two thirds of the P. tremula draft genome assembly on to the expected 19 chromosomes, providing us with the first chromosome-scale assembly for P. tremula (Table 2). We then use this resource to estimate variation in recombination rates across the P. tremula genome and compare these results to recombination rates based on linkage disequilibrium in a large number of unrelated individuals. We also assess how variation in recombination rates is associated with a number of genomic features, such as gene density, repeat density and methylation levels. We find that recombination rates obtained from the two methods largely agree, although the LD-based method identifies a number of genomic regions with very high recombination rates that the map-based method fails to detect. Linkage map and LD-based estimates of recombination rates are positively correlated and show similar correlations with other genomic features, showing that both methods can accurately infer recombination rate variation across the genome. Recombination rates are positively correlated with gene density and negatively correlated with repeat density and methylation levels, suggesting that recombination is largely directed toward gene regions in P. tremula.
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2.
  • Arefin, Badrul, et al. (författare)
  • The Immune Phenotype of Three Drosophila Leukemia Models
  • 2017
  • Ingår i: G3. - 2160-1836 .- 2160-1836. ; 7:7, s. 2139-2149
  • Tidskriftsartikel (refereegranskat)abstract
    • Many leukemia patients suffer from dysregulation of their immune system, making them more susceptible to infections and leading to general weakening (cachexia). Both adaptive and innate immunity are affected. The fruit fly Drosophila melanogaster has an innate immune system, including cells of the myeloid lineage (hemocytes). To study Drosophila immunity and physiology during leukemia, we established three models by driving expression of a dominant-active version of the Ras oncogene (Ras(V12)) alone or combined with knockdowns of tumor suppressors in Drosophila hemocytes. Our results show that phagocytosis, hemocyte migration to wound sites, wound sealing, and survival upon bacterial infection of leukemic lines are similar to wild type. We find that in all leukemic models the two major immune pathways (Toll and Imd) are dysregulated. Toll-dependent signaling is activated to comparable extents as after wounding wild-type larvae, leading to a proinflammatory status. In contrast, Imd signaling is suppressed. Finally, we notice that adult tissue formation is blocked and degradation of cell masses during metamorphosis of leukemic lines, which is akin to the state of cancer-dependent cachexia. To further analyze the immune competence of leukemic lines, we used a natural infection model that involves insect-pathogenic nematodes. We identified two leukemic lines that were sensitive to nematode infections. Further characterization demonstrates that despite the absence of behavioral abnormalities at the larval stage, leukemic larvae show reduced locomotion in the presence of nematodes. Taken together, this work establishes new Drosophila models to study the physiological, immunological, and behavioral consequences of various forms of leukemia.
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3.
  • Bachmann, Jörg A., et al. (författare)
  • Targeted Long-Read Sequencing of a Locus Under Long-Term Balancing Selection in Capsella
  • 2018
  • Ingår i: G3. - 2160-1836 .- 2160-1836. ; 8:4, s. 1327-1333
  • Tidskriftsartikel (refereegranskat)abstract
    • Rapid advances in short-read DNA sequencing technologies have revolutionized population genomic studies, but there are genomic regions where this technology reaches its limits. Limitations mostly arise due to the difficulties in assembly or alignment to genomic regions of high sequence divergence and high repeat content, which are typical characteristics for loci under strong long-term balancing selection. Studying genetic diversity at such loci therefore remains challenging. Here, we investigate the feasibility and error rates associated with targeted long-read sequencing of a locus under balancing selection. For this purpose, we generated bacterial artificial chromosomes (BACs) containing the Brassicaceae S-locus, a region under strong negative frequency-dependent selection which has previously proven difficult to assemble in its entirety using short reads. We sequence S-locus BACs with single-molecule long-read sequencing technology and conduct de novo assembly of these S-locus haplotypes. By comparing repeated assemblies resulting from independent long-read sequencing runs on the same BAC clone we do not detect any structural errors, suggesting that reliable assemblies are generated, but we estimate an indel error rate of 5.7x10(-5). A similar error rate was estimated based on comparison of Illumina short-read sequences and BAC assemblies. Our results show that, until de novo assembly of multiple individuals using long-read sequencing becomes feasible, targeted long-read sequencing of loci under balancing selection is a viable option with low error rates for single nucleotide polymorphisms or structural variation. We further find that short-read sequencing is a valuable complement, allowing correction of the relatively high rate of indel errors that result from this approach.
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4.
  • Bahrampour, Shahrzad, et al. (författare)
  • Ctr9, a Key Component of the Paf1 Complex, Affects Proliferation and Terminal Differentiation in the Developing Drosophila Nervous System
  • 2016
  • Ingår i: G3. - : Genetics Society of America. - 2160-1836 .- 2160-1836. ; 6:10, s. 3229-3239
  • Tidskriftsartikel (refereegranskat)abstract
    • The Paf1 protein complex (Paf1C) is increasingly recognized as a highly conserved and broadly utilized regulator of a variety of transcriptional processes. These include the promotion of H3K4 and H3K36 trimethylation, H2BK123 ubiquitination, RNA Pol II transcriptional termination, and also RNA-mediated gene silencing. Paf1C contains five canonical protein components, including Paf1 and Ctr9, which are critical for overall complex integrity, as well as Rtf1, Leo1, and Cdc73/Parafibromin(Hrpt2)/Hyrax. In spite of a growing appreciation for the importance of Paf1C from yeast and mammalian studies, there has only been limited work in Drosophila. Here, we provide the first detailed phenotypic study of Ctr9 function in Drosophila. We found that Ctr9 mutants die at late embryogenesis or early larval life, but can be partly rescued by nervous system reexpression of Ctr9. We observed a number of phenotypes in Ctr9 mutants, including increased neuroblast numbers, increased nervous system proliferation, as well as downregulation of many neuropeptide genes. Analysis of cell cycle and regulatory gene expression revealed upregulation of the E2f1 cell cycle factor, as well as changes in Antennapedia and Grainy head expression. We also found reduction of H3K4me3 modification in the embryonic nervous system. Genome-wide transcriptome analysis points to additional downstream genes that may underlie these Ctr9 phenotypes, revealing gene expression changes in Notch pathway target genes, cell cycle genes, and neuropeptide genes. In addition, we find significant effects on the gene expression of metabolic genes. These findings reveal that Ctr9 is an essential gene that is necessary at multiple stages of nervous system development, and provides a starting point for future studies of the Paf1C in Drosophila.
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5.
  • Basu, Swaraj, et al. (författare)
  • A Catalogue of Putative cis-Regulatory Interactions Between Long Non-coding RNAs and Proximal Coding Genes Based on Correlative Analysis Across Diverse Human Tumors
  • 2018
  • Ingår i: G3-Genes Genomes Genetics. - 2160-1836. ; 8:6, s. 2019-2025
  • Tidskriftsartikel (refereegranskat)abstract
    • Antisense transcripts and other long non-coding RNAs are pervasive in mammalian cells, and some of these molecules have been proposed to regulate proximal protein-coding genes in cis. For example, non-coding transcription can contribute to inactivation of tumor suppressor genes in cancer, and antisense transcripts have been implicated in the epigenetic inactivation of imprinted genes. However, our knowledge is still limited and more such regulatory interactions likely await discovery. Here, we make use of available gene expression data from a large compendium of human tumors to generate hypotheses regarding non-coding-to-coding cis-regulatory relationships with emphasis on negative associations, as these are less likely to arise for reasons other than cis-regulation. We document a large number of possible regulatory interactions, including 193 coding/non-coding pairs that show expression patterns compatible with negative cis-regulation. Importantly, by this approach we capture several known cases, and many of the involved coding genes have known roles in cancer. Our study provides a large catalog of putative non-coding/coding cis-regulatory pairs that may serve as a basis for further experimental validation and characterization.
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6.
  • Berlin Kolm, Sofia, et al. (författare)
  • Polymorphism and Divergence in Two Willow Species, Salix viminalis L. and Salix schwerinii E. Wolf
  • 2011
  • Ingår i: G3. - : Genetics Society of America: G3 / Genetics Society of America. - 2160-1836. ; 1, s. 387-400
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated species divergence, present and past gene flow, levels of nucleotide polymorphism, and linkage disequilibrium in two willows from the plant genus Salix. Salix belongs together with Populus to the Salicaceae family; however, most population genetic studies of Salicaceae have been performed in Populus, the model genus in forest biology. Here we present a study on two closely related willow species Salix viminalis and S. schwerinii, in which we have resequenced 33 and 32 nuclear gene segments representing parts of 18 nuclear loci in 24 individuals for each species. We used coalescent simulations and estimated the split time to around 600,000 years ago and found that there is currently limited gene flow between the species. Mean intronic nucleotide diversity across gene segments was slightly higher in S. schwerinii (pi(i) = 0.00849) than in S. viminalis (pi(i) = 0.00655). Compared with other angiosperm trees, the two willows harbor intermediate levels of silent polymorphisms. The decay of linkage disequilibrium was slower in S. viminalis compared with S. schwerinii, and we speculate that this is due to different demographic histories as S. viminalis has been partly domesticated in Europe.
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7.
  • Berlin, Sofia, et al. (författare)
  • Polymorphism and divergence of two willow species, Salix viminalis L. and Salix schwerinii E. Wolf
  • 2011
  • Ingår i: G3. - 2160-1836 .- 2160-1836. ; 1:5, s. 387-400
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated species divergence, present and past gene flow, levels of nucleotide polymorphism, and linkage disequilibrium in two willows from the plant genus Salix. Salix belongs together with Populus to the Salicaceae family; however, most population genetic studies of Salicaceae have been performed in Populus, the model genus in forest biology. Here we present a study on two closely related willow species Salix viminalis and S. schwerinii, in which we have resequenced 33 and 32 nuclear gene segments representing parts of 18 nuclear loci in 24 individuals for each species. We used coalescent simulations and estimated the split time to around 600,000 years ago and found that there is currently limited gene flow between the species. Mean intronic nucleotide diversity across gene segments was slightly higher in S. schwerinii (πi = 0.00849) than in S. viminalis (πi = 0.00655). Compared with other angiosperm trees, the two willows harbor intermediate levels of silent polymorphisms. The decay of linkage disequilibrium was slower in S. viminalis compared with S. schwerinii, and we speculate that this is due to different demographic histories as S. viminalis has been partly domesticated in Europe.
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8.
  • Bernhardsson, Carolina, et al. (författare)
  • An Ultra-Dense Haploid Genetic Map for Evaluating the Highly Fragmented Genome Assembly of Norway Spruce (Picea abies)
  • 2019
  • Ingår i: G3. - : Genetics Society of America. - 2160-1836 .- 2160-1836. ; 9:5, s. 1623-1632
  • Tidskriftsartikel (refereegranskat)abstract
    • Norway spruce (Picea abies (L.) Karst.) is a conifer species of substanital economic and ecological importance. In common with most conifers, the P. abies genome is very large (similar to 20 Gbp) and contains a high fraction of repetitive DNA. The current P. abies genome assembly (v1.0) covers approximately 60% of the total genome size but is highly fragmented, consisting of >10 million scaffolds. The genome annotation contains 66,632 gene models that are at least partially validated (), however, the fragmented nature of the assembly means that there is currently little information available on how these genes are physically distributed over the 12 P. abies chromosomes. By creating an ultra-dense genetic linkage map, we anchored and ordered scaffolds into linkage groups, which complements the fine-scale information available in assembly contigs. Our ultra-dense haploid consensus genetic map consists of 21,056 markers derived from 14,336 scaffolds that contain 17,079 gene models (25.6% of the validated gene models) that we have anchored to the 12 linkage groups. We used data from three independent component maps, as well as comparisons with previously published Picea maps to evaluate the accuracy and marker ordering of the linkage groups. We demonstrate that approximately 3.8% of the anchored scaffolds and 1.6% of the gene models covered by the consensus map have likely assembly errors as they contain genetic markers that map to different regions within or between linkage groups. We further evaluate the utility of the genetic map for the conifer research community by using an independent data set of unrelated individuals to assess genome-wide variation in genetic diversity using the genomic regions anchored to linkage groups. The results show that our map is sufficiently dense to enable detailed evolutionary analyses across the P. abies genome.
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9.
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10.
  • Brandt, Monika, et al. (författare)
  • Imputation-Based Fine-Mapping Suggests That Most QTL in an Outbred Chicken Advanced Intercross Body Weight Line Are Due to Multiple, Linked Loci
  • 2017
  • Ingår i: G3. - : Genetics Society of America: G3 / Genetics Society of America. - 2160-1836 .- 2160-1836. ; 7:1, s. 119-128
  • Tidskriftsartikel (refereegranskat)abstract
    • The Virginia chicken lines have been divergently selected for juvenile body weight for more than 50 generations. Today, the high- and low-weight lines show a >12-fold difference for the selected trait, 56-d body weight. These lines provide unique opportunities to study the genetic architecture of long-term, single-trait selection. Previously, several quantitative trait loci (QTL) contributing to weight differences between the lines were mapped in an F2-cross between them, and these were later replicated and fine-mapped in a nine-generation advanced intercross of them. Here, we explore the possibility to further increase the fine-mapping resolution of these QTL via a pedigree-based imputation strategy that aims to better capture the genetic diversity in the divergently selected, but outbred, founder lines. The founders of the intercross were high-density genotyped, and then pedigree-based imputation was used to assign genotypes throughout the pedigree. Imputation increased the marker density 20-fold in the selected QTL, providing 6911 markers for the subsequent analysis. Both single-marker association and multi-marker backward-elimination analyses were used to explore regions associated with 56-d body weight. The approach revealed several statistically and population structure independent associations and increased the mapping resolution. Further, most QTL were also found to contain multiple independent associations to markers that were not fixed in the founder populations, implying a complex underlying architecture due to the combined effects of multiple, linked loci perhaps located on independent haplotypes that still segregate in the selected lines.
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