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Sökning: WFRF:(Jern Patric)

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1.
  • Barrio, Alvaro Martinez, et al. (författare)
  • The First Sequenced Carnivore Genome Shows Complex Host-Endogenous Retrovirus Relationships
  • 2011
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:5, s. e19832-
  • Tidskriftsartikel (refereegranskat)abstract
    • Host-retrovirus interactions influence the genomic landscape and have contributed substantially to mammalian genome evolution. To gain further insights, we analyzed a female boxer (Canis familiaris) genome for complexity and integration pattern of canine endogenous retroviruses (CfERV). Intriguingly, the first such in-depth analysis of a carnivore species identified 407 CfERV proviruses that represent only 0.15% of the dog genome. In comparison, the same detection criteria identified about six times more HERV proviruses in the human genome that has been estimated to contain a total of 8% retroviral DNA including solitary LTRs. These observed differences in man and dog are likely due to different mechanisms to purge, restrict and protect their genomes against retroviruses. A novel group of gammaretrovirus-like CfERV with high similarity to HERV-Fc1 was found to have potential for active retrotransposition and possibly lateral transmissions between dog and human as a result of close interactions during at least 10.000 years. The CfERV integration landscape showed a non-uniform intra-and inter-chromosomal distribution. Like in other species, different densities of ERVs were observed. Some chromosomal regions were essentially devoid of CfERVs whereas other regions had large numbers of integrations in agreement with distinct selective pressures at different loci. Most CfERVs were integrated in antisense orientation within 100 kb from annotated protein-coding genes. This integration pattern provides evidence for selection against CfERVs in sense orientation relative to chromosomal genes. In conclusion, this ERV analysis of the first carnivorous species supports the notion that different mammals interact distinctively with endogenous retroviruses and suggests that retroviral lateral transmissions between dog and human may have occurred.
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2.
  • Benachenhou, Farid, et al. (författare)
  • Evolutionary Conservation of Orthoretroviral Long Terminal Repeats (LTRs) and ab initio Detection of Single LTRs in Genomic Data
  • 2009
  • Ingår i: PLos ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:4, s. e5179-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Retroviral LTRs, paired or single, influence the transcription of both retroviral and non-retroviral genomic sequences. Vertebrate genomes contain many thousand endogenous retroviruses (ERVs) and their LTRs. Single LTRs are difficult to detect from genomic sequences without recourse to repetitiveness or presence in a proviral structure. Understanding of LTR structure increases understanding of LTR function, and of functional genomics. Here we develop models of orthoretroviral LTRs useful for detection in genomes and for structural analysis. PRINCIPAL FINDINGS: Although mutated, ERV LTRs are more numerous and diverse than exogenous retroviral (XRV) LTRs. Hidden Markov models (HMMs), and alignments based on them, were created for HML- (human MMTV-like), general-beta-, gamma- and lentiretroviruslike LTRs, plus a general-vertebrate LTR model. Training sets were XRV LTRs and RepBase LTR consensuses. The HML HMM was most sensitive and detected 87% of the HML LTRs in human chromosome 19 at 96% specificity. By combining all HMMs with a low cutoff, for screening, 71% of all LTRs found by RepeatMasker in chromosome 19 were found. HMM consensus sequences had a conserved modular LTR structure. Target site duplications (TG-CA), TATA (occasionally absent), an AATAAA box and a T-rich region were prominent features. Most of the conservation was located in, or adjacent to, R and U5, with evidence for stem loops. Several of the long HML LTRs contained long ORFs inserted after the second A rich module. HMM consensus alignment allowed comparison of functional features like transcriptional start sites (sense and antisense) between XRVs and ERVs. CONCLUSION: The modular conserved and redundant orthoretroviral LTR structure with three A-rich regions is reminiscent of structurally relaxed Giardia promoters. The five HMMs provided a novel broad range, repeat-independent, ab initio LTR detection, with prospects for greater generalisation, and insight into LTR structure, which may aid development of LTR-targeted pharmaceuticals.
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4.
  • Blomberg, Jonas, et al. (författare)
  • Towards a retrovirus database, RetroBank
  • 2010
  • Ingår i: Centennial Retrovirus Meeting. - Bologna, Italy : Medimond. - 9788875875862 ; , s. 19-22
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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5.
  • Brattås, Per Ludvik, et al. (författare)
  • TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells
  • 2017
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 18:1, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Endogenous retroviruses (ERVs), which make up 8% of the human genome, have been proposed to participate in the control of gene regulatory networks. In this study, we find a region- and developmental stage-specific expression pattern of ERVs in the developing human brain, which is linked to a transcriptional network based on ERVs. We demonstrate that almost 10,000, primarily primate-specific, ERVs act as docking platforms for the co-repressor protein TRIM28 in human neural progenitor cells, which results in the establishment of local heterochromatin. Thereby, TRIM28 represses ERVs and consequently regulates the expression of neighboring genes. These results uncover a gene regulatory network based on ERVs that participates in control of gene expression of protein-coding transcripts important for brain development.
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6.
  • Chen, Junfeng, et al. (författare)
  • Functional differences between TSHR alleles associate with variation in spawning season in Atlantic herring
  • 2021
  • Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The underlying molecular mechanisms that determine long day versus short day breeders remain unknown in any organism. Atlantic herring provides a unique opportunity to examine the molecular mechanisms involved in reproduction timing, because both spring and autumn spawners exist within the same species. Although our previous whole genome comparisons revealed a strong association of TSHR alleles with spawning seasons, the functional consequences of these variants remain unknown. Here we examined the functional significance of six candidate TSHR mutations strongly associated with herring reproductive seasonality. We show that the L471M missense mutation in the spring-allele causes enhanced cAMP signaling. The best candidate non-coding mutation is a 5.2kb retrotransposon insertion upstream of the TSHR transcription start site, near an open chromatin region, which is likely to affect TSHR expression. The insertion occurred prior to the split between Pacific and Atlantic herring and was lost in the autumn-allele. Our study shows that strongly associated coding and non-coding variants at the TSHR locus may both contribute to the regulation of seasonal reproduction in herring. Junfeng Chen et al. examine potential functional consequences of reproduction timing-associated TSHR alleles segregating in Atlantic herring. By comparing fish that spawn during the spring to those that spawn in the autumn, they find that the spring-allele is correlated with enhanced cAMP signaling and that both coding and non-coding variants in the TSHR locus contribute to seasonal reproduction.
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7.
  • Delhomme, Nicolas, et al. (författare)
  • Serendipitous Meta-Transcriptomics : The Fungal Community of Norway Spruce (Picea abies)
  • 2015
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:9
  • Tidskriftsartikel (refereegranskat)abstract
    • After performing de novo transcript assembly of >1 billion RNA-Sequencing reads obtained from 22 samples of different Norway spruce (Picea abies) tissues that were not surface sterilized, we found that assembled sequences captured a mix of plant, lichen, and fungal transcripts. The latter were likely expressed by endophytic and epiphytic symbionts, indicating that these organisms were present, alive, and metabolically active. Here, we show that these serendipitously sequenced transcripts need not be considered merely as contamination, as is common, but that they provide insight into the plant's phyllosphere. Notably, we could classify these transcripts as originating predominantly from Dothideomycetes and Leotiomycetes species, with functional annotation of gene families indicating active growth and metabolism, with particular regards to glucose intake and processing, as well as gene regulation.
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8.
  • Edvardsen, Rolf Brudvik, et al. (författare)
  • Heterochiasmy and the establishment of gsdf as a novel sex determining gene in Atlantic halibut
  • 2022
  • Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 18:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Atlantic Halibut (Hippoglossus hippoglossus) has a X/Y genetic sex determination system, but the sex determining factor is not known. We produced a high-quality genome assembly from a male and identified parts of chromosome 13 as the Y chromosome due to sequence divergence between sexes and segregation of sex genotypes in pedigrees. Linkage analysis revealed that all chromosomes exhibit heterochiasmy, i.e. male-only and female-only meiotic recombination regions (MRR/FRR). We show that FRR/MRR intervals differ in nucleotide diversity and repeat class content and that this is true also for other Pleuronectidae species. We further show that remnants of a Gypsy-like transposable element insertion on chr13 promotes early male specific expression of gonadal somatic cell derived factor (gsdf). Less than 4.5 MYA, this male-determining element evolved on an autosomal FRR segment featuring pre-existing male meiotic recombination barriers, thereby creating a Y chromosome. Our findings indicate that heterochiasmy may facilitate the evolution of genetic sex determination systems relying on linkage of sexually antagonistic loci to a sex-determining factor. Author summaryEven closely related fish species can have different sex chromosomes, but this turn-over of sex determination systems is poorly understood. Here, we used large-scale genome sequencing to determine the DNA sequence of the Atlantic halibut chromosomes and compared sequencing data from males and females to identify the sex chromosomes. We show that males have much higher gene activity of the gene gonadal somatic cell derived factor (gsdf), which is located on the sex chromosomes and has a role in testicular development. The genome contains many mobile DNA sequences, transposable elements (TEs), one placed in front of gsdf, enhancing its activity. This made gsdf the sex determining factor, thereby creating a new Y-chromosome. We further describe how all Atlantic halibut chromosomes behave similar to sex chromosomes in that most regions only recombine in one sex. This phenomenon may contribute to the rapid turn-over of genetic sex determination systems in fish. Our results highlight the molecular events creating a new Y-chromosome and show that the new Atlantic halibut Y was formed less than 4.5 million years ago. Future studies in Atlantic halibut and closely related species can shed light on mechanisms contributing to sex chromosome evolution in fish.
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9.
  • Fasching, Liana, et al. (författare)
  • TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor Cells.
  • 2015
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 10:1, s. 20-28
  • Tidskriftsartikel (refereegranskat)abstract
    • TRIM28 is a corepressor that mediates transcriptional silencing by establishing local heterochromatin. Here, we show that deletion of TRIM28 in neural progenitor cells (NPCs) results in high-level expression of two groups of endogenous retroviruses (ERVs): IAP1 and MMERVK10C. We find that NPCs use TRIM28-mediated histone modifications to dynamically regulate transcription and silencing of ERVs, which is in contrast to other somatic cell types using DNA methylation. We also show that derepression of ERVs influences transcriptional dynamics in NPCs through the activation of nearby genes and the expression of long noncoding RNAs. These findings demonstrate a unique dynamic transcriptional regulation of ERVs in NPCs. Our results warrant future studies on the role of ERVs in the healthy and diseased brain.
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10.
  • Forsman, Anna, et al. (författare)
  • Development of broadly targeted human endogenous gammaretroviralpol-based real time PCRs Quantitation of RNA expression in human tissues
  • 2005
  • Ingår i: Journal of Virological Methods. - : Elsevier BV. - 0166-0934 .- 1879-0984. ; 129:1, s. 16-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Endogenous retroviral sequences (ERVs) are dynamic genomic components with profound influences on gene expression and genomic structure. Their extent of expression is not well known. Several broadly targeted real-time reverse transcription PCR (QPCRs) systems for surveillance of RNA expression of the major groups of human gammaretroviral ERVs were constructed. The highly conserved reverse transcriptase (RT) and integrase (IN) domains of the pol gene were used as targets for the PCRs, which were both probe-based (TaqMan) and probe-less (SYBR Green). Different levels of primer and probe degeneracy, with or without inosine, were tested. Several of the PCRs had sensitivities of a few HERV nucleic acid copies per PCR reaction. Specificities were approximately as expected from the fit of primers and probes. Gammaretroviral HERV RNA expression was studied in different human tissues. Each HERV group had a specific pattern of expression. HERV-E was highly expressed in testis, HERV-I/T in brain and testis, HERV-H in brain and testis, while HERV-W was highly expressed in placenta. Gammaretroviral RNA was not detected in plasma from 50 blood donors in saliva from 20 persons. In conclusion, a set of tools for investigation of gammaretroviral HERV RNA expression was created.
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