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| 2. |
- Bi, Huijuan, et al.
(författare)
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A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken
- 2023
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 19:4
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Tidskriftsartikel (refereegranskat)abstract
- The biochemical pathway regulating the synthesis of yellow/red pheomelanin is less well characterized than the synthesis of black/brown eumelanin. Inhibitor of gold (IG phenotype) is a plumage colour variant in chicken that provides an opportunity to further explore this pathway since the recessive allele (IG) at this locus is associated with a defect in the production of pheomelanin. IG/IG homozygotes display a marked dilution of red pheomelanin pigmentation, whilst black pigmentation (eumelanin) is only slightly affected. Here we show that a 2-base pair insertion (frame-shift mutation) in the 5th exon of the Catechol-O-methyltransferase containing domain 1 gene (COMTD1), expected to cause a complete or partial loss-of-function of the COMTD1 enzyme, shows complete concordance with the IG phenotype within and across breeds. We show that the COMTD1 protein is localized to mitochondria in pigment cells. Knockout of Comtd1 in a mouse melanocytic cell line results in a reduction in pheomelanin metabolites and significant alterations in metabolites of glutamate/glutathione, riboflavin, and the tricarboxylic acid cycle. Furthermore, COMTD1 overexpression enhanced cellular proliferation following chemical-induced transfection, a potential inducer of oxidative stress. These observations suggest that COMTD1 plays a protective role for melanocytes against oxidative stress and that this supports their ability to produce pheomelanin.
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| 3. |
- Carneiro, Miguel, et al.
(författare)
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Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6200, s. 1074-1079
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Tidskriftsartikel (refereegranskat)abstract
- The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.
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| 5. |
- Henningsson, Anna J., 1972-, et al.
(författare)
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Genome-wide DNA Methylation Profiling in Lyme Neuroborreliosis Reveals Altered Methylation Patterns of HLA Genes
- 2024
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Ingår i: Journal of Infectious Diseases. - : OXFORD UNIV PRESS INC. - 0022-1899 .- 1537-6613. ; 229:4, s. 1209-1214
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Tidskriftsartikel (refereegranskat)abstract
- Lyme neuroborreliosis (LNB) is a complex neuroinflammatory disorder caused by Borrelia burgdorferi, which is transmitted through tick bites. Epigenetic alterations, specifically DNA methylation (DNAm), could play a role in the host immune response during infection. In this study, we present the first genome-wide analysis of DNAm in peripheral blood mononuclear cells from patients with LNB and those without LNB. Using a network-based approach, we highlighted HLA genes at the core of these DNAm changes, which were found to be enriched in immune-related pathways. These findings shed light on the role of epigenetic modifications in the LNB pathogenesis that should be confirmed and further expanded upon in future studies. We present the first genome-wide analysis of DNA methylation in peripheral blood mononuclear cells from patients with and those without the tick-borne infection Lyme neuroborreliosis (LNB). Our findings show that LNB is associated with immune-related DNA methylation changes.
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| 6. |
- Huoman, Johanna, et al.
(författare)
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Epigenetic rewiring of pathways related to odour perception in immune cells exposed to SARS-CoV-2 in vivo and in vitro
- 2022
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Ingår i: Epigenetics. - New York, NY, United States : Taylor & Francis. - 1559-2294 .- 1559-2308. ; 17:13, s. 1875-1891
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Tidskriftsartikel (refereegranskat)abstract
- A majority of SARS-CoV-2 recoverees develop only mild-to-moderate symptoms, while some remain completely asymptomatic. Although viruses, including SARS-CoV-2, may evade host immune responses by epigenetic mechanisms including DNA methylation, little is known about whether these modifications are important in defence against and healthy recovery from COVID-19 in the host. To this end, epigenome-wide DNA methylation patterns from COVID-19 convalescents were compared to uninfected controls from before and after the pandemic. Peripheral blood mononuclear cell (PBMC) DNA was extracted from uninfected controls, COVID-19 convalescents, and symptom-free individuals with SARS-CoV-2-specific T cell-responses, as well as from PBMCs stimulated in vitro with SARS-CoV-2. Subsequently, the Illumina MethylationEPIC 850K array was performed, and statistical/bioinformatic analyses comprised differential DNA methylation, pathway over-representation, and module identification analyses. Differential DNA methylation patterns distinguished COVID-19 convalescents from uninfected controls, with similar results in an experimental SARS-CoV-2 infection model. A SARS-CoV-2-induced module was identified in vivo, comprising 66 genes of which six (TP53, INS, HSPA4, SP1, ESR1, and FAS) were present in corresponding in vitro analyses. Over-representation analyses revealed involvement in Wnt, muscarinic acetylcholine receptor signalling, and gonadotropin-releasing hormone receptor pathways. Furthermore, numerous differentially methylated and network genes from both settings interacted with the SARS-CoV-2 interactome. Altered DNA methylation patterns of COVID-19 convalescents suggest recovery from mild-to-moderate SARS-CoV-2 infection leaves longstanding epigenetic traces. Both in vitro and in vivo exposure caused epigenetic modulation of pathways thataffect odour perception. Future studies should determine whether this reflects host-induced protective antiviral defense or targeted viral hijacking to evade host defence.
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| 7. |
- Karlsson, Lovisa, et al.
(författare)
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A differential DNA methylome signature of pulmonary immune cells from individuals converting to latent tuberculosis infection
- 2021
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Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Tuberculosis (TB), caused by Mycobacterium tuberculosis, spreads via aerosols and the first encounter with the immune system is with the pulmonary-resident immune cells. The role of epigenetic regulations in the immune cells is emerging and we have previously shown that macrophages capacity to kill M. tuberculosis is reflected in the DNA methylome. The aim of this study was to investigate epigenetic modifications in alveolar macrophages and T cells in a cohort of medical students with an increased risk of TB exposure, longitudinally. DNA methylome analysis revealed that a unique DNA methylation profile was present in healthy subjects who later developed latent TB during the study. The profile was reflected in a different overall DNA methylation distribution as well as a distinct set of differentially methylated genes (DMGs). The DMGs were over-represented in pathways related to metabolic reprogramming of macrophages and T cell migration and IFN-gamma production, pathways previously reported important in TB control. In conclusion, we identified a unique DNA methylation signature in individuals, with no peripheral immune response to M. tuberculosis antigen who later developed latent TB. Together the study suggests that the DNA methylation status of pulmonary immune cells can reveal who will develop latent TB infection.
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| 8. |
- Krali, Olga, et al.
(författare)
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Multimodal classification of molecular subtypes in pediatric acute lymphoblastic leukemia
- 2023
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Ingår i: npj Precision Oncology. - : Springer Nature. - 2397-768X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Genomic analyses have redefined the molecular subgrouping of pediatric acute lymphoblastic leukemia (ALL). Molecular subgroups guide risk-stratification and targeted therapies, but outcomes of recently identified subtypes are often unclear, owing to limited cases with comprehensive profiling and cross-protocol studies. We developed a machine learning tool (ALLIUM) for the molecular subclassification of ALL in retrospective cohorts as well as for up-front diagnostics. ALLIUM uses DNA methylation and gene expression data from 1131 Nordic ALL patients to predict 17 ALL subtypes with high accuracy. ALLIUM was used to revise and verify the molecular subtype of 281 B-cell precursor ALL (BCP-ALL) cases with previously undefined molecular phenotype, resulting in a single revised subtype for 81.5% of these cases. Our study shows the power of combining DNA methylation and gene expression data for resolving ALL subtypes and provides a comprehensive population-based retrospective cohort study of molecular subtype frequencies in the Nordic countries.
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| 9. |
- Nikesjö, Frida, et al.
(författare)
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Defining post-acute COVID-19 syndrome (PACS) by an epigenetic biosignature in peripheral blood mononuclear cells
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Post-Acute COVID-19 Syndrome (PACS) has been defined as symptoms persisting after clearance of a COVID-19 infection. We have previously demonstrated that alterations in DNA methylation (DNAm) status persists in individuals who recovered from a COVID-19 infection, but it is currently unknown if PACS is associated with epigenetic changes. We compared DNAm patterns in patients with PACS with those in controls and in healthy COVID-19 convalescents and found a unique DNAm signature in PACS patients. This signature unravelled modified pathways that regulate angiotensin II and muscarinic receptor signalling and protein-protein interaction networks that have bearings on vesicle formation and mitochondrial function.
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| 10. |
- Nikesjö, Frida, et al.
(författare)
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Defining post-acute COVID-19 syndrome (PACS) by an epigenetic biosignature in peripheral blood mononuclear cells
- 2022
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Ingår i: Clinical Epigenetics. - : BioMed Central Ltd.. - 1868-7075 .- 1868-7083. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Post-acute COVID-19 syndrome (PACS) has been defined as symptoms persisting after clearance of a COVID-19 infection. We have previously demonstrated that alterations in DNA methylation (DNAm) status persist in individuals who recovered from a COVID-19 infection, but it is currently unknown if PACS is associated with epigenetic changes. We compared DNAm patterns in patients with PACS with those in controls and in healthy COVID-19 convalescents and found a unique DNAm signature in PACS patients. This signature unravelled modified pathways that regulate angiotensin II and muscarinic receptor signalling and protein–protein interaction networks that have bearings on vesicle formation and mitochondrial function.
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