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  • 1.
    Aliakbari, Massume
    et al.
    Department of Crop Production and Plant Breeding, Shiraz University, Shiraz, Iran.
    Cohen, Stephen P.
    Department of Plant Pathology, The Ohio State University, USA.
    Lindlöf, Angelica
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Shamloo-Dashtpagerdi, Roohollah
    Department of Agriculture and Natural Resources, Higher Education Center of Eghlid, Iran.
    Rubisco activase A (RcaA) is a central node in overlapping gene network of drought and salinity in Barley (Hordeum vulgare L.) and may contribute to combined stress tolerance2021In: Plant physiology and biochemistry (Paris), ISSN 0981-9428, E-ISSN 1873-2690, Vol. 161, p. 248-258Article in journal (Refereed)
    Abstract [en]

    Co-occurrence of abiotic stresses, especially drought and salinity, is a natural phenomenon in field conditions and is worse for crop production than any single stress. Nowadays, rigorous methods of meta-analysis and systems biology have made it possible to perform cross-study comparisons of single stress experiments, which can uncover main overlapping mechanisms underlying tolerance to combined stress. In this study, a meta-analysis of RNA-Seq data was conducted to obtain the overlapping gene network of drought and salinity stresses in barley (Hordeum vulgare L.), which identified Rubisco activase A (RcaA) as a hub gene in the dual-stress response. Thereafter, a greenhouse experiment was carried out using two barley genotypes with different abiotic stress tolerance and evaluated several physiochemical properties as well as the expression profile and protein activity of RcaA. Finally, machine learning analysis was applied to uncover relationships among combined stress tolerance and evaluated properties. We identified 441 genes which were differentially expressed under both drought and salinity stress. Results revealed that the photosynthesis pathway and, in particular, the RcaA gene are major components of the dual-stress responsive transcriptome. Comparative physiochemical and molecular evaluations further confirmed that enhanced photosynthesis capability, mainly through regulation of RcaA expression and activity as well as accumulation of proline content, have a significant association with combined drought and salinity stress tolerance in barley. Overall, our results clarify the importance of RcaA in combined stress tolerance and may provide new insights for future investigations. 

  • 2.
    Behboudi, Afrouz
    et al.
    CMB-Genetics, Göteborg University, Sweden.
    Levan, Göran
    CMB-Genetics, Göteborg University, Sweden.
    Hedrich, Hans J.
    Zentrales Tierlabor, Medizinische Hochschule Hannover, Germany.
    Klinga-Levan, Karin
    CMB-Genetics, Göteborg University, Sweden.
    High-density marker loss of heterozygosity analysis of rat chromosome 10 in endometrial adenocarcinoma2001In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 32, no 4, p. 330-341Article in journal (Refereed)
    Abstract [en]

    Endometrial cancer is a disease with serious impact on the human population, but not much is known about genetic factors involved in this complex disease. Female BDII rats are genetically predisposed to spontaneous endometrial carcinoma, and the BDII inbred strain provides an experimental animal model for endometrial carcinoma development. In the present study, BDII females were crossed with males from two nonsusceptible inbred rat strains. Endometrial adenocarcinomas (EACs) developed in a proportion of the F1 and F2 progeny. We screened 18 EAC solid tumors and 9 EAC cell cultures for loss of heterozygosity (LOH) using fluorescent-PCR-based marker allelotyping methodology with 47 microsatellite markers covering the proximal part of rat chromosome 10 (RNO10). Conclusive evidence was obtained for LOH/deletion involving about 56 cM in the proximal part of RNO10 in DNA from six out of seven informative tumor cell cultures. Analysis of the solid tumors confirmed the presence of LOH in this part of RNO10 in 14 of 17 informative tumors. However, from the studies in the solid tumors it appeared that in fact three separate segments in the proximal part of RNO10 were affected. These three LOH/deletion regions were located approximately in cytogenetic bands 10q11-12, 10q22, and 10q24. © 2001 Wiley-Liss, Inc.

  • 3.
    Behboudi, Afrouz
    et al.
    Göteborg University Inst. of Biomedicine, Clinical Genetics, Gothenburg, Sweden.
    Nordlander, Carola
    Göteborg University Inst. of Cell and Molecular Biology, Genetics, Gothenburg, Sweden.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Karlsson, Sandra
    University of Skövde, School of Life Sciences.
    Evidence for a tumor suppressor locus distal to Tp53 – a study in experimental endometrial adenocarcinoma2007In: European Journal of Cancer Supplements, ISSN 1359-6349, E-ISSN 1878-1217, Vol. 5, no 4, p. 62-62Article in journal (Other academic)
  • 4.
    Behboudi, Afrouz
    et al.
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Roshani, Leyla
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Kost-Alimova, Marija
    Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
    Sjöstrand, Eleonor
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Montelius-Alatalo, Kerstin
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Röhme, Dan
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Klinga-Levan, Karin
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Ståhl, Fredrik
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Detailed chromosomal and radiation hybrid mapping in the proximal part of rat Chromosome 10 and gene order comparison with mouse and human2002In: Mammalian Genome, ISSN 0938-8990, E-ISSN 1432-1777, Vol. 13, no 6, p. 302-309Article in journal (Refereed)
    Abstract [en]

    The rat provides valuable and sometimes unique models of human complex diseases. To fully exploit the rat models in biomedical research, it is important to have access to detailed knowledge of the rat genome organization as well as its relation to the human genome. Rat Chromosome 10 (RNO10) harbors several important cancer-related genes. Deletions in the proximal part of RNO10 were repeatedly found in a rat model for endometrial cancer. To identify functional and positional candidate genes in the affected region, we used radiation hybrid (RH) mapping and single- and dual-color fluorescence in situ hybridization (FISH) techniques to construct a detailed chromosomal map of the proximal part of RNO10. The regional localization of 14 genes, most of them cancer-related (Grin2a, Gspt1, Crebbp, Gfer, Tsc2, Tpsb1, Il9r, Il4, Irf1, Csf2, Sparc, Tp53, Thra1, Gh1), and of five microsatellite markers ( D10Mit10, D10Rat42, D10Rat50, D10Rat72, and D10Rat165) was determined on RNO10. For a fifteenth gene, Ppm1b, which had previously been assigned to RNO10, the map position was corrected to RNO6q12-q13.

  • 5.
    Behboudi, Afrouz
    et al.
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Roshani, Leyla
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Lundin, Lisa
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Ståhl, Fredrik
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Klinga-Levan, Karin
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Levan, Göran
    Department of Cell and Molecular Biology-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    The Functional Significance of Absence: The Chromosomal Segment Harboring Tp53 Is Absent from the T55 Rat Radiation Hybrid Mapping Panel2002In: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 79, no 6, p. 844-848Article in journal (Refereed)
    Abstract [en]

    The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2–6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.

  • 6.
    Behboudi, Afrouz
    et al.
    Department of Cell and Molecular Biology, Lundberg Laboratory, Göteborg University, Sweden.
    Sjöstrand, Eleonor
    Department of Cell and Molecular Biology, Lundberg Laboratory, Göteborg University, Sweden.
    Gómez-Fabre, P.
    Department of Cell and Molecular Biology, Lundberg Laboratory, Göteborg University, Sweden.
    Sjöling, Åsa
    Department of Cell and Molecular Biology, Lundberg Laboratory, Göteborg University, Sweden.
    Taib, Z.
    Department of Mathematics, Chalmers University of Technology, Göteborg, Sweden.
    Klinga-Levan, Karin
    Department of Cell and Molecular Biology, Lundberg Laboratory, Göteborg University, Sweden.
    Ståhl, Fredrik
    Department of Cell and Molecular Biology, Lundberg Laboratory, Göteborg University, Sweden.
    Levan, Göran
    Department of Cell and Molecular Biology, Lundberg Laboratory, Göteborg University, Sweden ; CMB-Genetics, Göteborg, Sweden.
    Evolutionary aspects of the genomic organization of rat chromosome 102002In: Cytogenetic and Genome Research, ISSN 1424-8581, E-ISSN 1424-859X, Vol. 96, no 1-4, p. 52-59Article in journal (Refereed)
    Abstract [en]

    Using FISH and RH mapping a chromosomal map of rat chromosome 10 (RNO10) was constructed. Our mapping data were complemented by other published data and the final map was compared to maps of mouse and human chromosomes. RNO10 contained segments homologous to mouse chromosomes (MMU) 11, 16 and 17, with evolutionary breakpoints between the three segments situated in the proximal part of RNO10. Near one of these breakpoints (between MMU17 and 11) we found evidence for an inversion ancestral to the mouse that was not ancestral to the condition in the rat. Within each of the chromosome segments identified, the gene order appeared to be largely conserved. This conservation was particularly clear in the long MMU11-homologous segment. RNO10 also contained segments homologous to three human chromosomes (HSA5, 16, 17). However, within each segment of conserved synteny were signs of more extensive rearrangements. At least 13 different evolutionary breakpoints were indicated in the rat-human comparison. In contrast to what was found between rat and mouse, the rat-human evolutionary breaks were distributed along the entire length of RNO10.

  • 7.
    Budnjo, Almir
    University of Skövde, School of Bioscience.
    Gene expression of MAP2K1 and Cyclin D1 in BDII rat model of Endometrial cancer2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Endometrial adenocarcinoma (EAC) is the most frequently diagnosed gynecological cancer of the female genital tract in the Western world. Research studies in EC is difficult to conduct on human tumor samples due to the complex nature of tumor arousal and genetic heterogeneousness in the human population. Therefore, inbred animal models can be promising tools to use in EC research due to similar histopathology and pathogenesis as humans. Studies performed on MAP2K1 and CCND1 has shown that their altered expression play a crucial role in carcinogenesis. CCND1 has been demonstrated to have oncogenic properties when overexpressed in human neoplasias.

    The aim of this study is to investigate gene expression levels of MAP2K1 and CCND1 in BDII rat model of endometrial adenocarcinoma cells. Quantitative real-time PCR was used to analyze expression levels of MAP2K1 and CCND1 genes in BDII/Han rat model of endometrial cancer cells using TaqMan approach. The differences in gene expression levels of MAP2K1 and CCND1 between pathologically EAC malignant and nonmalignant cells showed an upregulation of MAP2K1 and CCND1 in EAC malignant cells. The analyzed data presented observable mean differences between MAP2K1 and CCND1 in several endometrial cell lines that were examined.

    Although no statistical significance was reached, an alteration in gene expression levels in malignant and nonmalignant endometrial cells could be observed. Furthermore, this present study shows observable upregulation of MAP2K1 and CCND1 in endometrial carcinoma cells vs. nonmalignant endometrium cells and encourages further investigation of the role of CCND1 and MAP2K genes in endometrial carcinogenesis.

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  • 8.
    Chen, Lei
    et al.
    University of Skövde, School of Humanities and Informatics.
    Nordlander, Carola
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Behboudi, Afrouz
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Sweden.
    Olsson, Björn
    University of Skövde, School of Humanities and Informatics.
    Klinga Levan, Karin
    University of Skövde, School of Life Sciences.
    Deriving evolutionary tree models of the oncogenesis of endometrial adenocarcinoma2007In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 120, no 2, p. 292-296Article in journal (Refereed)
    Abstract [en]

    Endometrial adenocarcinoma (EAC) is the fourth leading cause of cancer death in women worldwide, but not much is known about the underlying genetic factors involved in the development of this complex disease. In the present work, we used 3 different algorithms to derive tree models of EAC oncogenesis from data on the frequencies of genomic alterations in rat chromosome 10 (RNO10). The tumor material was derived from progenies of crosses between the EAC susceptible BDII inbred rat strain and two non susceptible inbred rat strains. Data from allelic imbalance scans of RNO10 with microsatellite markers on solid tumor material and corresponding tissue cultures were used. For the analysis, RNO10 was divided into 24 segments containing a total of 59 informative microsatellite markers. The derived tree models show that genomic alterations have occurred in 11 of the 24 segments. In addition, the models provide information about the likely order of the alterations as well as their relationship with each other. Interestingly, there was a high degree of consistency among the different tree models and with the results of previous-studies, which supports the reliability of the tree models. Our results may be extended into a general approach for tree modeling of whole genome alterations during oncogenesis. (c) 2006 Wiley-Liss, Inc.

  • 9.
    Dahl-Halvarsson, Martin
    et al.
    University of Gothenburg, Gothenburg, Sweden.
    Olive, Montse
    Institut Investigació Biomèdica de Bellvitge – Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.
    Pokrzywa, Malgorzata
    University of Gothenburg, Gothenburg, Sweden.
    Ejeskär, Katarina
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Palmer, Ruth H.
    University of Gothenburg, Gothenburg, Sweden.
    Uv, Anne Elisabeth
    University of Gothenburg, Gothenburg, Sweden.
    Tajsharghi, Homa
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Drosophila model of myosin myopathy rescued by overexpression of a TRIM-protein family member2018In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 28, p. E6566-E6575Article in journal (Refereed)
    Abstract [en]

    Myosin is a molecular motor indispensable for body movement and heart contractility. Apart from pure cardiomyopathy, mutations in MYH7 encoding slow/β-cardiac myosin heavy chain also cause skeletal muscle disease with or without cardiac involvement. Mutations within the α-helical rod domain of MYH7are mainly associated with Laing distal myopathy. To investigate the mechanisms underlying the pathology of the recurrent causative MYH7 mutation (K1729del), we have developed a Drosophila melanogaster model of Laing distal myopathy by genomic engineering of the Drosophila Mhc locus. Homozygous MhcK1728del animals die during larval/pupal stages, and both homozygous and heterozygous larvae display reduced muscle function. Flies expressing only MhcK1728del in indirect flight and jump muscles, and heterozygous MhcK1728del animals, were flightless, with reduced movement and decreased lifespan. Sarcomeres of MhcK1728del mutant indirect flight muscles and larval body wall muscles were disrupted with clearly disorganized muscle filaments. Homozygous MhcK1728del larvae also demonstrated structural and functional impairments in heart muscle, which were not observed in heterozygous animals, indicating a dose-dependent effect of the mutated allele. The impaired jump and flight ability and the myopathy of indirect flight and leg muscles associated with MhcK1728del were fully suppressed by expression of Abba/Thin, an E3-ligase that is essential for maintaining sarcomere integrity. This model of Laing distal myopathy in Drosophila recapitulates certain morphological phenotypic features seen in Laing distal myopathy patients with the recurrent K1729del mutation. Our observations that Abba/Thin modulates these phenotypes suggest that manipulation of Abba/Thin activity levels may be beneficial in Laing distal myopathy.

  • 10.
    Dnyansagar, Rohit
    University of Skövde, School of Life Sciences.
    Investigation of phylogenetic relationships using microRNA sequences and secondary structures2010Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    MicroRNAs are important biomolecules for regulating biological processes. Moreover, the secondary structure of microRNA is important for its activity and has been used previously as a mean for finding unknown microRNAs. A phylogenetic study of the microRNA secondary structure reveals more information than its primary sequence, because the primary sequence can undergo mutations that give rise to different phylogenetic relationships, whereas the secondary structure is more robust against mutations and therefore sometimes  more informative.

    Here we constructed a phylogenetic tree entirely based on microRNA secondary structures using tools PHYLIP (Felsenstein, 1995) and RNAforester (Matthias Höchsmann, 2003, Hochsmann et al., 2004), and compared the overall topology and clusters with the phylogenetic tree constructed using microRNA sequence. The purpose behind this comparison was to investigate the sequence and structure similarity in phylogenetic context and also to investigate if functionally similar microRNA genes are closer in their structure-derived phylogenetic tree.

    Our phylogenetic comparison shows that the sequence similarity has hardly any effect on the structure similarity in the phylogenetic tree. MicroRNAs that have similar function are closer in the phylogenetic tree based on secondary structure than its respective sequence phylogeny. Hence, this approach can be very useful in predicting the functions of the new microRNAs whose function is yet to be known, since the function of the miRNAs heavily relies on its secondary structure.

     

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    FULLTEXT01
  • 11.
    Ekelund Ugge, Gustaf Magnus Oskar
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Lund University.
    Transcriptional biomarkers of toxicity – powerful tools or random noise?: An applied perspective from studies on bivalves2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aquatic organisms are constantly at risk of being exposed to potentially harmful chemical compounds of natural or anthropogenic origin. Biological life can for instance respond to chemical stressors by changes in gene expression, and thus, certain gene transcripts can potentially function as biomarkers, i.e. early warnings, of toxicity and chemical stress. A major challenge for biomarker application is the extrapolation of transcriptional data to potential effects at the organism level or above. Importantly, successful biomarker use also requires basal understanding of how to distinguish actual responses from background noise. The aim of this thesis is, based on response magnitude and variation, to evaluate the biomarker potential in a set of putative transcriptional biomarkers of general toxicity and chemical stress.

    Specifically, I addressed a selection of six transcripts involved in cytoprotection and oxidative stress: catalase (cat), glutathione-S-transferase (gst), heat shock proteins 70 and 90 (hsp70, hsp90), metallothionein (mt) and superoxide dismutase (sod). Moreover, I used metal exposures to serve as a proxy for general chemical stress, and due to their ecological relevance and nature as sedentary filter-feeders, I used bivalves as study organisms.

    In a series of experiments, I tested transcriptional responses in the freshwater duck mussel, Anodonta anatina, exposed to copper or an industrial wastewater effluent, to address response robustness and sensitivity, and potential controlled (e.g. exposure concentration) and random (e.g. gravidness) sources of variation. In addition, I performed a systematic review and meta-analysis on transcriptional responses in metal exposed bivalves to (1) evaluate what responses to expect from arbitrary metal exposures, (2) assess the influence from metal concentration (expressed as toxic unit), exposure time and analyzed tissue, and (3) address potential impacts from publication bias in the scientific literature.

    Response magnitudes were generally small in relationship to the observed variation, both for A. anatina and bivalves in general. The expected response to an arbitrary metal exposure would generally be close to zero, based on both experimental observations and on the estimated impact from publication bias. Although many of the transcripts demonstrated concentration-response relationships, large background noise might in practice obscure the small responses even at relatively high exposures. As demonstrated in A. anatina under copper exposure, this can be the case already for single species under high resolution exposures to single pollutants. As demonstrated by the meta-regression, this problem can only be expected to increase further upon extrapolation between different species and exposure scenarios, due to increasing heterogeneity and random variation. Similar patterns can also be expected for time-dependent response variation, although the meta-regression revealed a general trend of slightly increasing response magnitude with increasing exposure times.

    In A. anatina, gravidness was identified as a source of random variability that can potentially affect the baseline of most assessed biomarkers, particularly when quantified in gills. Response magnitudes and variability in this species were generally similar for selected transcripts as for two biochemical biomarkers included for comparison (AChE, GST), suggesting that the transcripts might not capture early warnings more efficiently than other molecular endpoints that are more toxicologically relevant. Overall, high concentrations and long exposure durations presumably increase the likelihood of a detectable transcriptional response, but not to an extent that justifies universal application as biomarkers of general toxicity and chemical stress. Consequently, without a strictly defined and validated application, this approach on its own appears unlikely to be successful for future environmental risk assessment and monitoring. Ultimately, efficient use of transcriptional biomarkers might require additional implementation of complementary approaches offered by current molecular techniques.

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    Gustaf M.O. Ekelund Ugge - PhD thesis
  • 12.
    Ferreira de Vilcinskas, Robherta
    University of Skövde, School of Bioscience.
    Identification of Lactobacillus species in honey using 16S rRNA gene sequencing2022Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Honey is a natural product composed of numeral substances and microorganisms. Although honey presents physicochemical properties that confer antimicrobial characteristics, certain microorganisms are still able to survive and multiply in honey. Some of these microorganisms are important to human health, such as Lactobacillus bacteria, which can be used as probiotic to improve human gastrointestinal condition. However, there is still a lack of knowledge about the microorganisms found in honey, and further research is necessary to better identify and understand these microorganisms. The aim of this study was to detect and identify Lactobacillus species from honey by sequencing the 16S ribosomal RNA gene with the universal primers 27F and 1492R. This was partly obtained by searching for Lactobacillus spp. directly in pure honey and after growing the unknown viable Lactobacillus spp. from honey in selective media. The microorganisms were isolated by centrifugation, had their DNA extracted, and only the bacterial 16S rRNA gene was amplified using Polymerase Chain Reaction and sequenced using the Oxford MinION Nanopore sequencing technology. EPI2ME, Oxford Nanopore Technology data analysis platform, was used to identify the bacteria. Results showed the presence of numeral Lactobacillus species in honey such as L. melliventris, L. mellifer, L. mellis, and L. helsinbgborgen, but in very low amounts. The analysis of honey samples was quite difficult. Low PCR product yield during the entire study, microscopic visualization and microbial analysis using fungicides supported the presence of fungi. In conclusion, a diversity of Lactobacillus spp. can be found in honey but in low quantities.

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  • 13.
    Hamta, A.
    et al.
    CMB-Genetics, Göteborg University, Sweden.
    Adamovic, T.
    CMB-Genetics, Göteborg University, Sweden.
    Samuelson, Emma
    CMB-Genetics, Göteborg University, Sweden.
    Helou, K.
    Department of Oncology, Göteborg University, Sweden.
    Behboudi, Afrouz
    CMB-Genetics, Göteborg University, Sweden.
    Levan, Göran
    CMB-Genetics, Göteborg University, Sweden ; CMB-Genetics, Göteborg, Sweden.
    Chromosome ideograms of the laboratory rat (Rattus norvegicus) based on high-resolution banding, and anchoring of the cytogenetic map to the DNA sequence by FISH in sample chromosomes2006In: Cytogenetic and Genome Research, ISSN 1424-8581, E-ISSN 1424-859X, Vol. 115, no 2, p. 158-168Article in journal (Refereed)
    Abstract [en]

    A detailed banded ideogram representation of the rat chromosomes was constructed based on actual G-banded prometaphase chromosomes. The approach yielded 535 individual bands, a significant increase compared to previously presented ideograms. The new ideogram was adapted to the existing band nomenclature. The gene locus positions in the rat draft DNA sequence were compared to the chromosomal positions as determined by dual-color FISH, using rat (RNO) chromosomes 6 and 15 and a segment of RNO4 as sample regions. It was found that there was generally an excellent correlation in the chromosome regions tested between the relative gene position in the DNA molecules and the sub-chromosomal localization by FISH and subsequent information transfer on ideograms from measurements of chromosomal images. However, in the metacentric chromosome (RNO15), the correlation was much better in the short arm than in the long arm, suggesting that the centromeric region may distort the linear relationship between the chromosomal image and the corresponding DNA molecule.

  • 14.
    Jelenkovic, Aline
    et al.
    Department of Social Research, University of Helsinki, Finland ; Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, Leioa, Spain.
    Dahl Aslan, Anna K.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden ; Institute of Gerontology and Aging Research Network - Jönköping (ARN-J), School of Health and Welfare, Jönköping University, Sweden.
    Silventoinen, Karri
    Department of Social Research, University of Helsinki, Finland ; Osaka University Graduate School of Medicine, Osaka University, Japan.
    Genetic and environmental influences on adult human height across birth cohorts from 1886 to 19942016In: eLIFE, E-ISSN 2050-084X, Vol. 5, article id e20320Article in journal (Refereed)
    Abstract [en]

    Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886–1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.

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  • 15.
    Jelenkovic, Aline
    et al.
    Department of Social Research, University of Helsinki, Finland ; Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, Leioa, Spain.
    Dahl Aslan, Anna K.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden ; Institute of Gerontology, School of Health Sciences, Jönköping University, Sweden.
    Silventoinen, Karri
    Department of Social Research, University of Helsinki, Finland ; Osaka University Graduate School of Medicine, Osaka University, Japan.
    Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project2015In: Twin Research and Human Genetics, ISSN 1832-4274, E-ISSN 1839-2628, Vol. 18, no 5, p. 557-570Article in journal (Refereed)
    Abstract [en]

    A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.

  • 16.
    Krettek, Alexandra
    et al.
    Division of Evolutionary Molecular Systematics, University of Lund, Lund, Sweden.
    Gullberg, Anette
    Division of Evolutionary Molecular Systematics, University of Lund, Lund, Sweden.
    Arnason, Ulfur
    Division of Evolutionary Molecular Systematics, University of Lund, Lund, Sweden.
    Sequence analysis of the complete mitochondrial DNA molecule of the hedgehog, Erinaceus europaeus, and the phylogenetic position of the Lipotyphla1995In: Journal of Molecular Evolution, ISSN 0022-2844, E-ISSN 1432-1432, Vol. 41, no 6, p. 952-957Article in journal (Refereed)
    Abstract [en]

    The sequence of the mitochondrial DNA (mtDNA) molecule of the European hedgehog (Erinaceus europaeus) was determined. The length of the sequence presented is 17,442 nucleotides (nt). The molecule is thus the largest eutherian mtDNA molecule so far reported. The organization of the molecule conforms with that of other eutherians, but the control region of the molecule is exceptionally long, 1,988 nt, due to the presence of repeated motifs at two different positions in the 3' part of the control region. The length of the control region is not absolute due to pronounced heteroplasmy caused by variable numbers of the motif TACGCA in one of the repetitive regions. The sequence presented includes 46 repeats of this type. The other repeated region is composed of different AT-rich repeats. This region was identical among four clones studied. Comparison of mitochondrial peptide-coding genes identified a separate position of the hedgehog among several mammalian orders. The concatenated protein sequence of the 13 peptide-coding genes was used in a phylogenetic study using the opossum as outgroup. The position of the hedgehog sequence was basal among the other eutherian sequences included: human, rat, mouse, cow, blue whale, harbor seal, and horse. The analysis did not resolve the relationship among carnivores, perissodactyls, and artiodactyls/cetaceans, suggesting a closer relationship among these orders than acknowledged by classical approaches.

  • 17.
    Magnusson, Rasmus
    et al.
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Bioinformatics, Department of Physics, Chemistry and Biology, Linköping University, Sweden.
    Tegnér, Jesper N.
    Biological and Environmental Sciences and Engineering Division, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia ; Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden ; Science for Life Laboratory, Solna, Sweden.
    Gustafsson, Mika
    Bioinformatics, Department of Physics, Chemistry and Biology, Linköping University, Sweden.
    Deep neural network prediction of genome-wide transcriptome signatures – beyond the Black-box2022In: npj Systems Biology and Applications, ISSN 2056-7189, Vol. 8, no 1, article id 9Article in journal (Refereed)
    Abstract [en]

    Prediction algorithms for protein or gene structures, including transcription factor binding from sequence information, have been transformative in understanding gene regulation. Here we ask whether human transcriptomic profiles can be predicted solely from the expression of transcription factors (TFs). We find that the expression of 1600 TFs can explain >95% of the variance in 25,000 genes. Using the light-up technique to inspect the trained NN, we find an over-representation of known TF-gene regulations. Furthermore, the learned prediction network has a hierarchical organization. A smaller set of around 125 core TFs could explain close to 80% of the variance. Interestingly, reducing the number of TFs below 500 induces a rapid decline in prediction performance. Next, we evaluated the prediction model using transcriptional data from 22 human diseases. The TFs were sufficient to predict the dysregulation of the target genes (rho = 0.61, P < 10−216). By inspecting the model, key causative TFs could be extracted for subsequent validation using disease-associated genetic variants. We demonstrate a methodology for constructing an interpretable neural network predictor, where analyses of the predictors identified key TFs that were inducing transcriptional changes during disease.

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  • 18.
    Nilipour, Yalda
    et al.
    Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Iran.
    Nafissi, Shahriar
    Tehran University of Medical Sciences, Iran.
    Tjust, Anton E.
    Umeå University, Sweden.
    Ravenscroft, Gianina
    The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Western Australia, Australia.
    Hossein-Nejad Nedai, Hamid
    Shahid Beheshti University of Medical Sciences, Iran.
    Taylor, Rhonda L.
    The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Western Australia.
    Varasteh, Vahid
    Shahid Beheshti University of Medical Sciences, Iran.
    Pedrosa Domellöf, Fatima
    Umeå University, Sweden.
    Zangi, Mahdi
    National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Iran.
    Tonekaboni, Seyed Hassan
    Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Iran.
    Olivé, M.
    IDIBELL-Hospital de Bellvitge, Barcelona, Spain.
    Kiiski, Kirsi
    Folkhälsan Institute of Genetics, Medicum, University of Helsinki, Finland.
    Sagath, L.
    Folkhälsan Institute of Genetics, Medicum, University of Helsinki, Finland.
    Davis, Mark R.
    Pathwest, QEII Medical Centre, Nedlands, Western Australia.
    Laing, Nigel G.
    The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Western Australia.
    Tajsharghi, Homa
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Western Australia, Australia.
    Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies2018In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 6, p. 841-847Article in journal (Refereed)
    Abstract [en]

    Background: Nemaline myopathy has been associated with mutations in twelve genes to date. However, for some patients diagnosed with nemaline myopathy, definitive mutations are not identified in the known genes, suggesting there are other genes involved. This study describes compound heterozygosity for rare variants in RYR3 in one such patient.

    Results: Clinical examination of the patient at 22 years of age revealed a long-narrow face, high arched palate and bilateral facial weakness. She had proximal weakness in all four limbs, mild scapular winging but no scoliosis. Muscle biopsy revealed wide variation in fibre size with type 1 fibre predominance and atrophy. Abundant nemaline bodies were located in perinuclear areas, subsarcolemmal and within the cytoplasm. No likely pathogenic mutations in known nemaline myopathy genes were identified. Copy number variation in known nemaline myopathy genes was excluded by nemaline myopathy targeted array-CGH. Next generation sequencing revealed compound heterozygous missense variants in the ryanodine receptor type 3 gene (RYR3).  RYR3 transcripts are expressed in human fetal and adult skeletal muscle as well as in human brain or cauda equina samples. Immunofluorescence of human skeletal muscle revealed a "single-row" appearance of RYR3, interspaced between the "double-rows" of RYR1 at each A-I junction.

    Conclusion: The results suggest that variants in RYR3 may cause a recessive muscle disease with pathological features including nemaline bodies. We characterize the expression pattern of RYR3 in human skeletal muscle and brain and the subcellular localization of RYR1 and RYR3 in human skeletal muscle.

  • 19.
    Nordlander, Carola
    et al.
    Lundberg Laboratory, CMB-Genetics, Göteborg University, Sweden ; Department of Pathology, Lundberg Laboratory for Cancer Research, Göteborg, Sweden.
    Behboudi, Afrouz
    Department of Pathology, Lundberg Laboratory for Cancer Research, Göteborg, Sweden.
    Levan, Göran
    Lundberg Laboratory, CMB-Genetics, Göteborg University, Sweden ; Department of Pathology, Lundberg Laboratory for Cancer Research, Göteborg, Sweden.
    Klinga Levan, Karin
    University of Skövde, School of Life Sciences.
    Allelic imbalance on chromosome 10 in rat endometrial adenocarcinomas2005In: Cancer Genetics and Cytogenetics, ISSN 0165-4608, E-ISSN 1873-4456, Vol. 156, no 2, p. 158-166Article in journal (Refereed)
    Abstract [en]

    Earlier work using comparative genome hybridization (CGH) has shown that rat chromosome 10 (RNO10) is frequently involved in cytogenetic aberrations in BDII rat endometrial adenocarcinomas (EAC). Relative reduction in copy number (chromosomal deletions) was seen in the proximal to middle part of the chromosome, whereas there were increases in copy number in the distal part. The occurrence of RNO10 aberrations was further analyzed in DNA from primary tumor material from 42 EACs and 3 benign endometrial tumors using allelotyping of microsatellite markers. We found frequently that there were 4 quite distinct RNO10 regions that exhibited allelic imbalance. Based on these findings we believe that genes with relevance to EAC tumor development are situated in each of these chromosome regions. Extrapolation of our microsatellite marker data to the rat draft DNA sequence will facilitate the definition of the regions at the level of the DNA and to select and characterize candidate genes within each of the affected chromosome regions.

  • 20.
    Nordlander, Carola
    et al.
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Gothenhurg, Sweden.
    Karlsson, Sandra
    University of Skövde, School of Life Sciences.
    Karlsson, Åsa
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Gothenhurg, Sweden ; Division of Medicine/Oncology, Stanford School of Medicine, Stanford, CA 94305, United States.
    Sjöling, Åsa
    Institute of Biomedicine, Department of Microbiology and Immunology, Göteborg University, Gothenburg, Sweden.
    Winnes, Marta
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Gothenhurg, Sweden ; Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Gothenburg, Sweden.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Behboudi, Afrouz
    Institute of Biomedicine, Department of Clinical Genetics, Göteborg University, Gothenburg, Sweden.
    Analysis of chromosome 10 aberrations in rat endometrial cancer: Evidence for a tumor suppressor locus distal to Tp532007In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 120, no 7, p. 1472-1481Article in journal (Refereed)
    Abstract [en]

    We have recently shown in the BDII rat model of human endometrial adenocarcinoma (EAC), rat chromosome 10 (RNO10) is frequently involved in chromosomal aberrations. In the present study, we investigated the association between RNO10 deletions, allelic imbalance (AI) at RNO10q24 and Tp53 mutation in 27 rat EAC tumors. We detected chromosomal breakage accompanied by loss of proximal and/or gain of distal parts of RNO10 in approximately 2/3 of the tumors. This finding is suggestive of a tumor suppressor activity encoded from the proximal RNO10. Given the fact that Tp53 is located at RNO10q24-q25, we then performed Tp53 mutation analysis. However, we could not find a strong correlation between AI/deletions at RNO10q24 and Tp53 mutation. Instead, the observed patterns for AI, chromosomal breaks and deletions suggest that major selection was directed against a region located close to, but distal of Tp53. In different human malignancies a similar situation of AI at chromosome band 17p13.3 (HSA17p13.3) unassociated with TP53 mutation has been observed. Although RNO10 is largely homologous to HSA17, the conservation with respect to gene order among them is not extensive. We utilized publicly available draft DNA sequences to study intrachromosomal rearrangement during the divergence between HSA17 and RNO10. By using reciprocal comparison of rat and human genome data, we could substantially narrow down the candidate tumor suppressor region in rat from 3 Mb to a chromosomal segment of about 0.5 Mb in size. These results provide scientific groundwork for identification of the putative tumor suppressor gene(s) at 17p13.3 in human tumors

  • 21.
    Nordlander, Carola
    et al.
    Department of Cellular and Molecular Biology-Genetics Lundberg Institute, Göteborg, Sweden.
    Samuelson, Emma
    Sahlgrenska Academy Department of Clinical Genetics, Göteborg University, Sweden.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Behboudi, Afrouz
    Recurrent Chromosome 10 Aberrations and Tp53 Mutations in Rat Endometrial Adenocarcinomas2008In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 617, p. 519-525Article in journal (Refereed)
    Abstract [en]

    Human genetic heterogeneity and differences in the environment and life style make analysis of complex diseases such as cancer difficult. By using inbred animal strains, the genetic variability can be minimized and the environmental factors can be reasonably controlled. Endometrial adenocarcinoma (EAC) is the most common gynecologic malignancy, ranking fourth in incidence among tumors in women. The inbred BDII rat strain is genetically prone to spontaneously develop hormone-related EAC, and can be used as a tool to investigate and characterize genetic changes in this tumor type. In the present project, BDII females were crossed to males from two nonsusceptible rat strains and F1, F2, and backcross progeny were produced. Genetic and molecular genetic analysis of tumors showed that rat chromosome 10 (RNO10) was frequently involved in genetic changes. Our data indicate that often there was loss of chromosomal material in the proximal to middle part of the chromosome followed by gains in distal RNO10. This suggested that there is a tumor suppressor gene(s) in the proximal to middle part of RNO10 and an oncogene(s) in the distal part of the chromosome with potential significance in EAC development. The Tp53 gene, located at band RNO10q24-q25, was a strong candidate target for the observed aberrations affecting the middle part of the chromosome. However, our Tp53 gene mutation analyses suggested that a second gene situated very close to Tp53 might be the main target for the observed pattern of genetic changes.

  • 22.
    Nourizadeh, Alireza
    University of Skövde, School of Bioscience. No.
    APC, BRAF and KRAS mutations, and MLH1, MGMT and CDKN2A expression analysis in Nepalese colorectal cancer patients.: -2017Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Colorectal cancer (CRC) is a common malignancy which develops due to old age and lifestyle factors, low percent of patients afflicted by a genetic disorders. Half of all colorectal cancer patients are diagnosed after metastasis. The high rate of the late detection, emphasizes on the requirement of convenient and inexpensive diagnostic methods for comprehensive screening programs. The aim of this study was to discover proto-oncogenes mutation and assessment of tumor suppressor genes expression. Formalin fixed paraffin embedded (FFPE) histologically verified colorectal cancer samples were used. APC, KRAS and BRAF mutations were investigated using polymerase chain reaction (PCR) fragments and direct sequencing. Gene expression assessment of MLH1, MGMT and CDKN2A were achieved via quantitative polymerase chain reaction (qPCR). In the present study we could detect a novel transversion heterozygous mutation in APC gene codon 1365 in three patients. BRAF codon 600 mutation were detected in one patient. KRAS codon 12 mutation was discovered in one sample and also a novel transition mutation in codon 15 was detected in 6 patients. In 80% of cases, MLH1 and MGMT expression were undetectable, in remaining 20%, MLH1 expression were reduced, but MGMT showed both reduced and increased expression compared to control. In 100% of patients CDKN2A expression was undetectable. The rate of mutations in predetermined hotspot codons and amount of uncommon mutations into APC, BRAF and KRAS in Nepalese patients indicates the requirement of further investigation in CRC patients from that part of the world. Also, the expression rate of MLH1, MGMT, CDKN2A and deficiency of an information source emphasizes the necessity of whole genome CRC expression profiling data to comparison and conclusion. 

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  • 23.
    Olsson, Björn E.
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Korsakova, Ekaterina S.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Anan'ina, Lyudmila N.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Pyankova, Anna A.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Mavrodi, Olga V.
    Department of Biological Sciences, The University of Southern Mississippi, USA.
    Plotnikova, Elena G.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Mavrodi, Dmitri V.
    Department of Biological Sciences, The University of Southern Mississippi, USA.
    Draft genome sequences of strains Salinicola socius SMB35T, Salinicola sp. MH3R3–1 and Chromohalobacter sp. SMB17 from the Verkhnekamsk potash mining region of Russia2017In: Standards in Genomic Sciences, E-ISSN 1944-3277, Vol. 12, no 39, p. 1-13Article in journal (Refereed)
    Abstract [en]

    Halomonads are moderately halophilic bacteria that are studied as models of prokaryotic osmoadaptation and sources of enzymes and chemicals for biotechnological applications. Despite the progress in understanding the diversity of these organisms, our ability to explain ecological, metabolic, and biochemical traits of halomonads at the genomic sequence level remains limited. This study addresses this gap by presenting draft genomes of Salinicola socius SMB35T, Salinicola sp. MH3R3-1 and Chromohalobacter sp. SMB17, which were isolated from potash mine tailings in the Verkhnekamsk salt deposit area of Russia. The analysis of these genomes confirmed the importance of ectoines and quaternary amines to the capacity of halomonads to tolerate osmotic stress and adapt to hypersaline environments. The study also revealed that Chromohalobacter and Salinicola share 75-90% of the predicted proteome, but also harbor a set of genus-specific genes, which in Salinicola amounted to approximately 0.5 Mbp. These genus-specific genome segments may contribute to the phenotypic diversity of the Halomonadaceae and the ability of these organisms to adapt to changing environmental conditions and colonize new ecological niches.

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  • 24.
    Samuelson, Emma
    et al.
    Sahlgrenska Academy Department of Clinical Genetics, Göteborg University, Sweden.
    Nordlander, Carola
    Department of Cellular and Molecular Biology-Genetics Lundberg Institute, Göteborg, Sweden.
    Levan, Göran
    Behboudi, Afrouz
    Amplification Studies of MET and Cdk6 in a Rat Endometrial Tumor Model and Their Correlation to Human Type I Endometrial Carcinoma Tumors2008In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 617, p. 511-517Article in journal (Refereed)
    Abstract [en]

    Cancer is known to be a genetic disease that is both polygenic and heterogeneous, in most cases involving changes in several genes in a stepwise fashion. The spectrum of individual genes involved in the initiation and progression of cancer is greatly influenced by genetic factors unique to each patient. A study of complex diseases such as cancer is complicated by the genetic heterogeneous background and environmental factors in the human population. Endometrial cancer (EC) is ranked fourth among invasive tumors in women. In Sweden, approximately 1300 women (27/100,000 women) are diagnosed annually. To be able to study the genetic alterations in cancer, the use of an animal model is very convenient. Females of the BDII strain are genetically predisposed to EC and 90% of female BDII rats develop EC during their lifetime. Thus, BDII rats have been used to model human EC with respect to the genetics of susceptibility and of tumor development. A set of rat EC tumors was analyzed using conventional cytogenetics and comparative genome hybridization (CGH). Chromosomal aberrations, i.e., gains, were found on rat chromosome 4 (RNO4). Using FISH analysis, we concluded that the Met oncogene and Cdk6 (cyclin-dependent kinase 6) were amplified in this set of EC tumors. The data from this investigation were used to analyze a set of human endometrial tumors for amplification of Cdk6 and Met. Our preliminary data are indicative for a good correlation between our findings in the BDII rat model for EAC and the situation in human EC. These data provide strong support for the use of animal model systems for better understanding and scrutinizing of human complex disease of cancer.

  • 25.
    Sandstedt, Mikael
    et al.
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Vukusic, Kristina
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Johansson, Markus
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Jonsson, Marianne
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Magnusson, Rasmus
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Hultén, Lillemor Mattsson
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Dellgren, Göran
    Molecular and Clinical Medicine, Cardiothoracic Surgery, University of Gothenburg, Sweden.
    Jeppsson, Anders
    Molecular and Clinical Medicine, Cardiothoracic Surgery, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lindahl, Anders
    Sahlgrenska University Hospital, Göteborg, University of Gothenburg, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Sandstedt, Joakim
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Regional transcriptomic profiling reveals immune system enrichment in nonfailing atria as well as all chambers of the failing human heart2023In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 325, no 6, p. H1430-H1445Article in journal (Refereed)
    Abstract [en]

    The different chambers of the human heart demonstrate regional physiological traits and may be differentially affected during pathologic remodeling, resulting in heart failure. Few previous studies have, however, characterized the different chambers at a transcriptomic level. We therefore conducted whole-tissue RNA sequencing and gene set enrichment analysis of biopsies collected from the four chambers of adult failing (n = 8) and nonfailing (n = 11) human hearts. Atria and ventricles demonstrated distinct transcriptional patterns. Compared to nonfailing ventricles, the transcriptional pattern of nonfailing atria was enriched for a large number of gene sets associated with cardiogenesis, the immune system and bone morphogenetic protein (BMP), transforming growth factor beta (TGF beta), MAPK/JNK and Wnt signaling. Differences between failing and nonfailing hearts were also determined. The transcriptional pattern of failing atria was distinct compared to that of nonfailing atria and enriched for gene sets associated with the innate and adaptive immune system, TGF beta/SMAD signaling, and changes in endothelial, smooth muscle cell and cardiomyocyte physiology. Failing ventricles were also enriched for gene sets associated with the immune system. Based on the transcriptomic patterns, upstream regulators associated with heart failure were identified. These included many immune response factors predicted to be similarly activated for all chambers of failing hearts. In summary, the heart chambers demonstrate distinct transcriptional patterns that differ between failing and nonfailing hearts. Immune system signaling may be a hallmark of all four heart chambers in failing hearts, and could constitute a novel therapeutic target.

  • 26.
    Shamloo-Dashtpagerdi, Roohollah
    et al.
    Department of Agriculture and Natural Resources, Higher Education Center of Eghlid, Eghlid, Iran.
    Lindlöf, Angelica
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Aliakbari, Massume
    Department of Crop Production and Plant Breeding, Shiraz University, Shiraz, Iran.
    Pirasteh-Anosheh, Hadi
    National Salinity Research Center, Agricultural Research, Education and Extension Organization, Yazd, Iran.
    Plausible association between drought stress tolerance of barley (Hordeum vulgare L.) and programmed cell death via MC1 and TSN1 genes2020In: Physiologia Plantarum, ISSN 0031-9317, E-ISSN 1399-3054, Vol. 170, no 1, p. 46-59Article in journal (Refereed)
    Abstract [en]

    Studying the drought-responsive transcriptome is of high interest as it can serve as a blueprint for stress adaptation strategies. Despite extensive studies in this area, there are still many details to be uncovered, such as the importance of each gene involved in the stress response as well as the relationship between these genes and the physiochemical processes governing stress tolerance. This study was designed to address such important details and to gain insights into molecular responses of barley (Hordeum vulgare L.) to drought stress. To that, we combined RNA-seq data analysis with field and greenhouse drought experiments in a systems biology approach. RNA-sequence analysis identified a total of 665 differentially expressed genes (DEGs) belonging to diverse functional categories. A gene network was derived from the DEGs, which comprised of a total of 131 nodes and 257 edges. Gene network topology analysis highlighted two programmed cell death (PCD) modulating genes, MC1 (metacaspase 1) and TSN1 (Tudor-SN 1), as important (hub) genes in the predicted network. Based on the field trial, a drought-tolerant and a drought-susceptible barley genotype was identified from eight tested cultivars. Identified genotypes exhibited different physiochemical characteristics, including proline content, chlorophyll concentration, percentage of electrolyte leakage and malondialdehyde content as well as expression profiles of MC1 and TSN1 genes. Machine learning and correspondence analysis revealed a significant relationship between drought tolerance and measured characteristics in the context of PCD. Our study provides new insights which bridge barley drought tolerance to PCD through MC1 and TSN1 pathway.

  • 27.
    Shamloo-Dashtpagerdi, Roohollah
    et al.
    Department of Agriculture and Natural Resources, Higher Education Center of Eghlid, Iran.
    Lindlöf, Angelica
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Nouripour-Sisakht, Javad
    Department of Plant Production and Genetics, College of Agricultural Engineering, Isfahan University of Technology, Iran.
    Unraveling the regulatory role of MYC2 on ASMT gene expression in wheat: Implications for melatonin biosynthesis and drought tolerance2023In: Physiologia Plantarum, ISSN 0031-9317, E-ISSN 1399-3054, Vol. 175, no 5, article id e14015Article in journal (Refereed)
    Abstract [en]

    Recognized for its multifaceted functions, melatonin is a hormone found in both animals and plants. In the plant kingdom, it plays diverse roles, regulating growth, development, and stress responses. Notably, melatonin demonstrates its significance by mitigating the effects of abiotic stresses like drought. However, understanding the precise regulatory mechanisms controlling melatonin biosynthesis genes, especially during monocots' response to stresses, requires further exploration. Seeking to understand the molecular basis of drought stress tolerance in wheat, we analyzed RNA-Seq libraries of wheat exposed to drought stress using bioinformatics methods. In light of our findings, we identified that the Myelocytomatosis oncogenes 2 (MYC2) transcription factor is a hub gene upstream of a main melatonin biosynthesis gene, N-acetylserotonin methyltransferase (ASMT), in the wheat drought response-gene network. Promoter analysis of the ASMT gene suggested that it might be a target gene of MYC2. We conducted a set of molecular and physiochemical assays along with robust machine learning approaches to elevate those findings further. MYC2 and ASMT were co-regulated under Jasmonate, drought, and a combination of them in the leaf tissues of wheat was detected. A meaningful correlation was observed among gene expression profiles, melatonin contents, photosynthetic activities, antioxidant enzyme activities, H2O2 levels, and plasma membrane damage. The results indicated an evident relationship between jasmonic acid and the melatonin biosynthesis pathway. Moreover, it seems that the MYC2-ASMT module might contribute to wheat drought tolerance by regulating melatonin contents. 

  • 28.
    Shamloo-Dashtpagerdia, Roohollah
    et al.
    Department of Agriculture and Natural Resources, Higher Education Center of Eghlid, Iran.
    Lindlöf, Angelica
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Niazi, Ali
    Institute of Biotechnology, Shiraz University, Iran.
    Pirasteh-Anosheh, Hadi
    National Salinity Research Center, Agricultural Research, Education and Extension Organization, Yazd, Iran.
    LOS2 gene plays a potential role in barley (Hordeum vulgare L.) salinity tolerance as a hub gene2019In: Molecular breeding, ISSN 1380-3743, E-ISSN 1572-9788, Vol. 39, no 8, article id 119Article in journal (Refereed)
    Abstract [en]

    Understanding how plants respond to salinity stress is essential for developing tolerant genotypes, to keep human food secure since it is threaten by climate changes and increasing population worldwide. Barley (Hordeum vulgare) is a crop that possesses various salinity tolerance mechanisms that remain to be explored. In this study, data from an RNA-Seq experiment in barley was analyzed to identify changes in genome activities as well as differentially expressed genes (DEGs) in response to salinity stress. A gene network was predicted among identified DEGs and was subjected to network topology analysis, which resulted in the prediction of a hub gene, namely low expression of osmotically responsive gene 2 (LOS2). LOS2 and its two hierarchical downstream genes, salt-tolerant zinc finger (ZAT10) and ascorbate peroxidase 1 (APX1), were used in a genome-wide association (GWA) survey to confirm their importance. A field experiment was conducted to recognize susceptible and tolerant genotypes among 10 different barley genotypes based on the principle component analysis (PCA) of stress-related indices. In a separate salinity experiment, two of the genotypes were assessed to assign their physiological and biochemical responses as well as to identify expression profiles of LOS2, ZAT10, and APX1. From the results, the activity of the barley genome was significantly altered toward response to stress. In total, 5692 DEGs were identified and the gene network derived from these genes contained 131 nodes and 257 edges. The identified genotypes clearly showed the difference in water status, osmolyte accumulation, cell membrane damages, and ion homeostasis as well as in expression profiles for studied genes during salinity stress. Our results suggest that LOS2 along with the ZAT10 and APX1 genes may serve as an important part of barley salinity stress tolerance pathways. To our knowledge, this is the first report on the role(s) of LOS2 in barley salinity stress tolerance in a gene network system.

  • 29.
    Shemirani, Mahnaz Irani
    et al.
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Tilevik, Andreas
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Jurcevic, Sanja
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Arnellos, Dimitrios
    1928 Diagnostics, Gothenburg, Sweden.
    Enroth, Helena
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Molecular Microbiology, Laboratory Medicine, Unilabs AB, Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Benchmarking of two bioinformatic workflows for the analysis of whole-genome sequenced Staphylococcus aureus collected from patients with suspected sepsis2023In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 23, no 1, p. 39-, article id 39Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The rapidly growing area of sequencing technologies, and more specifically bacterial whole-genome sequencing, could offer applications in clinical microbiology, including species identification of bacteria, prediction of genetic antibiotic susceptibility and virulence genes simultaneously. To accomplish the aforementioned points, the commercial cloud-based platform, 1928 platform (1928 Diagnostics, Gothenburg, Sweden) was benchmarked against an in-house developed bioinformatic pipeline as well as to reference methods in the clinical laboratory.

    METHODS: Whole-genome sequencing data retrieved from 264 Staphylococcus aureus isolates using the Illumina HiSeq X next-generation sequencing technology was used. The S. aureus isolates were collected during a prospective observational study of community-onset severe sepsis and septic shock in adults at Skaraborg Hospital, in the western region of Sweden. The collected isolates were characterized according to accredited laboratory methods i.e., species identification by MALDI-TOF MS analysis and phenotypic antibiotic susceptibility testing (AST) by following the EUCAST guidelines. Concordance between laboratory methods and bioinformatic tools, as well as concordance between the bioinformatic tools was assessed by calculating the percent of agreement.

    RESULTS: There was an overall high agreement between predicted genotypic AST and phenotypic AST results, 98.0% (989/1006, 95% CI 97.3-99.0). Nevertheless, the 1928 platform delivered predicted genotypic AST results with lower very major error rates but somewhat higher major error rates compared to the in-house pipeline. There were differences in processing times i.e., minutes versus hours, where the 1928 platform delivered the results faster. Furthermore, the bioinformatic workflows showed overall 99.4% (1267/1275, 95% CI 98.7-99.7) agreement in genetic prediction of the virulence gene characteristics and overall 97.9% (231/236, 95% CI 95.0-99.2%) agreement in predicting the sequence types (ST) of the S. aureus isolates.

    CONCLUSIONS: Altogether, the benchmarking disclosed that both bioinformatic workflows are able to deliver results with high accuracy aiding diagnostics of severe infections caused by S. aureus. It also illustrates the need of international agreement on quality control and metrics to facilitate standardization of analytical approaches for whole-genome sequencing based predictions.

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  • 30.
    Shumkova, E. S.
    et al.
    A N Bach Institute of Biochemistry, RAS, Moscow, Russia / Perm State National Research University, Perm, Russia.
    Olsson, Björn E.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Perm State National Research University, Perm, Russia.
    Plotnikova, E. G.
    Perm State National Research University, Perm, Russia / Institute of Ecology and Genetics of Microorganisms, UB RAS, Perm, Russia.
    Organization of Biphenyl and Polychlorinated Biphenyls Destruction Genes in Rhodococcus ruber P252015In: Russian Journal of Immunology, ISSN 1028-7221, Vol. 9, no 2, p. 624-626Article in journal (Refereed)
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  • 31.
    Shumkova, Ekaterina
    et al.
    A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russia a/ Perm State University, Perm, Russia.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Kudryavtseva, Anna
    Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
    Plotnikova, Elena
    Perm State University, Perm, Russia / Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Draft Genome Sequence of Rhodococcus ruber Strain P25: an Active Polychlorinated Biphenyl Degrader2015In: Genome Announcements, E-ISSN 2169-8287, Vol. 3, no 5, article id e00990-15Article in journal (Refereed)
    Abstract [en]

    We report the 5,728,255-bp draft genome sequence of Rhodococcus ruber P25, isolated from a soil polluted with halogenated aromatic compounds in the city of Perm, Russia. The strain degrades polychlorinated biphenyls and a broad range of aromatic compounds. It possesses genes that mediate the degradation of biphenyls/polychlorinated biphenyls, naphthalene, and monoaromatic compounds.

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  • 32.
    Silventoinen, Karri
    et al.
    Department of Social Research, University of Helsinki, Finland ; Osaka University Graduate School of Medicine, Osaka University, Japan.
    Dahl Aslan, Anna K.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden ; Institute of Gerontology, School of Health Sciences, Jönköping University, Sweden.
    Kaprio, Jaakko
    Department of Public Health, University of Helsinki, Finland ; National Institute for Health and Welfare, Helsinki, Finland Institute for Molecular Medicine FIMM, Helsinki, Finland.
    The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits2015In: Twin Research and Human Genetics, ISSN 1832-4274, E-ISSN 1839-2628, Vol. 18, no 4, p. 348-360Article in journal (Refereed)
    Abstract [en]

    For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

  • 33.
    Silventoinen, Karri
    et al.
    Department of Social Research, Faculty of Social Sciences, University of Helsinki, Finland ; Center for Twin Research, Osaka University Graduate School of Medicine, Osaka, Japan.
    Jelenkovic, Aline
    Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country, Leioa, Spain ; Department of Public Health, University of Helsinki, Finland.
    Sund, Reijo
    Department of Social Research, Faculty of Social Sciences, University of Helsinki, Finland ; Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
    Latvala, Antti
    Department of Social Research, Faculty of Social Sciences, University of Helsinki, Finland.
    Honda, Chika
    Center for Twin Research, Osaka University Graduate School of Medicine, Osaka, Japan.
    Inui, Fujio
    Center for Twin Research, Osaka University Graduate School of Medicine, Osaka, Japan ; Faculty of Health Science, Kio University, Nara, Japan.
    Tomizawa, Rie
    Center for Twin Research, Osaka University Graduate School of Medicine, Osaka, Japan.
    Watanabe, Mikio
    Center for Twin Research, Osaka University Graduate School of Medicine, Osaka, Japan.
    Sakai, Norio
    Center for Twin Research, Osaka University Graduate School of Medicine, Osaka, Japan.
    Rebato, Esther
    Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, Leioa, Spain.
    Busjahn, Andreas
    HealthTwiSt GmbH, Berlin, Germany.
    Tyler, Jessica
    Twins Research Australia, Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, VIC, Australia.
    Hopper, John L.
    Twins Research Australia, Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, VIC, Australia ; Department of Epidemiology, School of Public Health, Seoul National University, Korea.
    Ordoñana, Juan R.
    Department of Human Anatomy and Psychobiology, University of Murcia, Spain ; IMIB-Arrixaca, Murcia, Spain.
    Sánchez-Romera, Juan F.
    Department of Human Anatomy and Psychobiology, University of Murcia, Spain ; IMIB-Arrixaca, Murcia, Spain.
    Colodro-Conde, Lucia
    Department of Human Anatomy and Psychobiology, University of Murcia, Spain ; Genetic Epidemiology Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
    Calais-Ferreira, Lucas
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Australia.
    Oliveira, Vinicius C.
    Pós‑Graduação em Reabilitação e Desempenho Funcional, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Brazil.
    Ferreira, Paulo H.
    Musculoskeletal Health Research Group, Faculty of Health Sciences, The University of Sydney, Australia.
    Medda, Emanuela
    Istituto Superiore di Sanità - Centre for Behavioural Sciences and Mental Health, Rome, Italy.
    Nisticò, Lorenza
    Istituto Superiore di Sanità - Centre for Behavioural Sciences and Mental Health, Rome, Italy.
    Toccaceli, Virgilia
    Istituto Superiore di Sanità - Centre for Behavioural Sciences and Mental Health, Rome, Italy.
    Derom, Catherine A.
    Centre of Human Genetics, University Hospitals Leuven, Belgium ; Department of Obstetrics and Gynaecology, Ghent University Hospitals, Belgium.
    Vlietinck, Robert F.
    Centre of Human Genetics, University Hospitals Leuven, Belgium.
    Loos, Ruth J. F.
    The Charles Bronfman Institute for Personalized Medicine, The Mindich Child Health and Development Institute, Icahn School of Medicine At Mount Sinai, New York, NY, USA.
    Siribaddana, Sisira H.
    Institute of Research and Development, Battaramulla, Sri Lanka ; Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka Saliyapura, Anuradhapura, Sri Lanka.
    Hotopf, Matthew
    Institute of Psychiatry Psychology and Neuroscience, King’s College London, UK ; South London and Maudsley NHS Foundation Trust, London, UK.
    Sumathipala, Athula
    Institute of Research and Development, Battaramulla, Sri Lanka ; Research Institute for Primary Care and Health Sciences, School for Primary Care Research (SPCR), Faculty of Health, Keele University, Stafordshire, UK.
    Rijsdijk, Fruhling
    Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, UK.
    Duncan, Glen E.
    Washington State Twin Registry, Washington State University - Health Sciences Spokane, Spokane, WA, USA.
    Buchwald, Dedra
    Washington State Twin Registry, Washington State University - Health Sciences Spokane, Spokane, WA, USA.
    Tynelius, Per
    Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
    Rasmussen, Finn
    Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
    Tan, Qihua
    Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
    Zhang, Dongfeng
    Department of Public Health, Qingdao University Medical College, Qingdao, China.
    Pang, Zengchang
    Department of Noncommunicable Diseases Prevention, Qingdao Centers for Disease Control and Prevention, Qingdao, China.
    Magnusson, Patrik K. E.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Pedersen, Nancy L.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Dahl Aslan, Anna K.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden ; Institute of Gerontology and Aging Research Network – Jönköping (ARN‑J), School of Health and Welfare, Jönköping University, Sweden.
    Hwang, Amie E.
    Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA ; USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
    Mack, Thomas M.
    Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA ; USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
    Krueger, Robert F.
    Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
    McGue, Matt
    Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
    Pahlen, Shandell
    Department of Psychology, University of California, Riverside, CA, USA.
    Brandt, Ingunn
    Division of Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway.
    Nilsen, Thomas S.
    Division of Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway.
    Harris, Jennifer R.
    Division of Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway.
    Martin, Nicholas G.
    Genetic Epidemiology Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
    Medland, Sarah E.
    Genetic Epidemiology Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
    Montgomery, Grant W.
    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
    Willemsen, Gonneke
    Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, The Netherlands.
    Bartels, Meike
    Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, The Netherlands.
    van Beijsterveldt, Catharina E. M.
    Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, The Netherlands.
    Franz, Carol E.
    Department of Psychiatry, University of California, San Diego, CA, USA.
    Kremen, William S.
    Department of Psychiatry, University of California, San Diego, CA, USA ; VA San Diego Center of Excellence for Stress and Mental Health, La Jolla, CA, USA.
    Lyons, Michael J.
    Department of Psychological and Brain Sciences, Boston University, MA, USA.
    Silberg, Judy L.
    Department of Human and Molecular Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
    Maes, Hermine H.
    Department of Human and Molecular Genetics, Psychiatry and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
    Kandler, Christian
    Department of Psychology, University of Bremen, Germany.
    Nelson, Tracy L.
    Department of Health and Exercise Sciences and Colorado School of Public Health, Colorado State University, Fort Collins, USA.
    Whitfield, Keith E.
    Psychology Department, Wayne State University, Detroit, MI, USA.
    Corley, Robin P.
    Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.
    Huibregtse, Brooke M.
    Institute of Behavioral Science, University of Colorado, Boulder, CO, USA.
    Gatz, Margaret
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden ; Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
    Butler, David A.
    Health and Medicine Division, The National Academies of Sciences, Engineering, and Medicine, Washington, DC, USA.
    Tarnoki, Adam D.
    Medical Imaging Centre, Semmelweis University, Budapest, Hungary ; Hungarian Twin Registry, Budapest, Hungary.
    Tarnoki, David L.
    Medical Imaging Centre, Semmelweis University, Budapest, Hungary ; Hungarian Twin Registry, Budapest, Hungary.
    Park, Hang A.
    Department of Epidemiology, School of Public Health, Seoul National University, Korea ; Department of Emergency Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
    Lee, Jooyeon
    Department of Epidemiology, School of Public Health, Seoul National University, Korea.
    Lee, Soo Ji
    Department of Epidemiology, School of Public Health, Seoul National University, Korea ; Institute of Health and Environment, Seoul National University, South Korea.
    Sung, Joohon
    Department of Epidemiology, School of Public Health, Seoul National University, Korea ; Institute of Health and Environment, Seoul National University, South Korea.
    Yokoyama, Yoshie
    Department of Public Health Nursing, Osaka City University, Japan.
    Sørensen, Thorkild I. A.
    Novo Nordisk Foundation Centre for Basic Metabolic Research (Section of Metabolic Genetics), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark ; Department of Public Health (Section of Epidemiology), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
    Boomsma, Dorret I.
    Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, The Netherlands.
    Kaprio, Jaakko
    Department of Public Health, University of Helsinki, Finland ; Institute for Molecular Medicine Finland FIMM, University of Helsinki, Finland.
    Genetic and environmental variation in educational attainment: an individual-based analysis of 28 twin cohorts2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 12681Article in journal (Refereed)
    Abstract [en]

    We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.

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  • 34.
    Silventoinen, Karri
    et al.
    Faculty of Social Sciences, Department of Social Research, University of Helsinki, Finland.
    Vuoksimaa, Eero
    Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Finland.
    Volanen, Salla-Maarit
    Folkhälsan Research Center, Helsinki, Finland ; Clinicum, Department of Public Health, University of Helsinki, Finland.
    Palviainen, Teemu
    Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Finland.
    Rose, Richard J.
    Department of Psychological & Brain Sciences, Indiana University, Bloomington, USA.
    Suominen, Sakari
    University of Skövde, School of Health Sciences. University of Skövde, Digital Health Research (DHEAR). Department of Public Health, University of Turku, Finland.
    Kaprio, Jaakko
    Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Finland.
    The genetic background of the associations between sense of coherence and mental health, self-esteem and personality2022In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 57, no 2, p. 423-433Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Sense of coherence (SOC) represents coping and can be considered an essential component of mental health. SOC correlates with mental health and personality, but the background of these associations is poorly understood. We analyzed the role of genetic factors behind the associations of SOC with mental health, self-esteem and personality using genetic twin modeling and polygenic scores (PGS).

    METHODS: Information on SOC (13-item Orientation of Life Questionnaire), four mental health indicators, self-esteem and personality (NEO Five Factor Inventory Questionnaire) was collected from 1295 Finnish twins at 20-27 years of age.

    RESULTS: In men and women, SOC correlated negatively with depression, alexithymia, schizotypal personality and overall mental health problems and positively with self-esteem. For personality factors, neuroticism was associated with weaker SOC and extraversion, agreeableness and conscientiousness with stronger SOC. All these psychological traits were influenced by genetic factors with heritability estimates ranging from 19 to 66%. Genetic and environmental factors explained these associations, but the genetic correlations were generally stronger. The PGS of major depressive disorder was associated with weaker, and the PGS of general risk tolerance with stronger SOC in men, whereas in women the PGS of subjective well-being was associated with stronger SOC and the PGSs of depression and neuroticism with weaker SOC.

    CONCLUSION: Our results indicate that a substantial proportion of genetic variation in SOC is shared with mental health, self-esteem and personality indicators. This suggests that the correlations between these traits reflect a common neurobiological background rather than merely the influence of external stressors.

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  • 35.
    Sjöling, Åsa
    et al.
    Department of Cell and Molecular Biology-Genetics, Göteborg, Sweden ; Department of Medical Microbiology and Immunology, Göteborg, Sweden.
    Walentinsson, Anna
    Department of Cell and Molecular Biology-Genetics, Göteborg, Sweden.
    Nordlander, Carola
    Department of Cell and Molecular Biology-Genetics, Göteborg, Sweden.
    Karlsson, Åsa
    Department of Cell and Molecular Biology-Genetics, Göteborg, Sweden.
    Behboudi, Afrouz
    Department of Cell and Molecular Biology-Genetics, Göteborg, Sweden.
    Samuelson, Emma
    Department of Cell and Molecular Biology-Genetics, Göteborg, Sweden.
    Levan, Göran
    Department of Cell and Molecular Biology-Genetics, Göteborg, Sweden.
    Röhme, Dan
    Department of Cell and Molecular Biology-Genetics, Göteborg, Sweden.
    Assessment of allele dosage at polymorphic microsatellite loci displaying allelic imbalance in tumors by means of quantitative competitive-polymerase chain reaction2005In: Cancer Genetics and Cytogenetics, ISSN 0165-4608, E-ISSN 1873-4456, Vol. 157, no 2, p. 97-103Article in journal (Refereed)
    Abstract [en]

    Analysis of allelic imbalance at polymorphic marker loci is usually employed to identify chromosomal regions affected by recurrent aberrations in tumor genomes. Such regions are likely to harbor genes involved in the onset and/or progression of cancer. Although often used to identify regions of loss of heterozygosity caused by deletions/rearrangements near tumor suppressor gene loci, allelic imbalance can also reflect regional amplification, indicating the presence of oncogenes. It is difficult to tell these two situations apart after ordinary polymerase chain reaction (PCR), but here we describe a method that distinguishes allelic loss from allelic gain. The level of allelic imbalance was determined by quantitative PCR (QPCR) in the presence of an internal control DNA that displayed a third allele at the locus studied. To validate the efficiency of allele quantitation, we analyzed an amplified region in a set of rat fibrosarcomas. In four tumor samples with amplification of the Met oncogene, we could show with QPCR that there was amplification of one of the alleles at a microsatellite marker located close to Met. QPCR may be useful for cancer studies because experiments may be predesigned for using either suitable microsatellite markers or the abundant and polymorphic poly-A tails of rodent identifier sequences.

  • 36.
    Sutkowska, Agnieszka
    et al.
    University of Agriculture in Krakow, Poland.
    Pasierbinski, Andrzej
    University of Silesia in Katowice, Poland.
    Warzecha, Tomasz
    University of Agriculture in Krakow, Poland.
    Mandal, Abul
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Mitka, Jozef
    Jagiellonian University in Krakow, Poland.
    Refugial pattern of Bromus erectus in Central Europe based on ISSR fingerprinting2013In: Acta Biologica Cracoviensia. Series Botanica, ISSN 0001-5296, E-ISSN 1898-0295, Vol. 55, no 2, p. 107-119Article in journal (Refereed)
    Abstract [en]

    We studied the thermophilous grass Bromus erectusin Central Europe to determine its pattern of populationgenetic structure and genetic diversity, using ISSR-PCR fingerprinting to analyze 200 individuals from 37 popu-lations.  We  found  three  genetic  groups  with  a  clear  geographic  structure,  based  on  a  Bayesian  approach.  Thefirst group occurred west and south of the Alps, the second east and north of the Alps, and the third was formedby four genetically depauperated populations in Germany. The populations from Germany formed a subset ofthe  Bohemian-Moravian  populations,  with  one  private  allele.  Two  differentiation  centers,  one  in  the  Atlantic-Mediterranean and the second in the Pannonian-Balkan area, were recognized by species distribution modeling.The geographic distribution of the genetic groups coincides with the syntaxonomic split of the Festuco-Brometeaclass into the Festucetalia valesiaceae and Brometalia erecti orders. We found a statistically significant decreasein mean ISSR bands per individual from south to north, and to a lesser extent from the east to west. The for-mer was explained by Holocene long-distance migrations from southern refugia, the latter by the difference inthe gradient of anthropopression. We hypothesize a cryptic northern shelter of the species in Central Europe inthe putative Moravian-Bohemian refugium.

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  • 37.
    Synnergren, Jane
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Améen, Caroline
    Cellartis, Gothenburg, Sweden.
    Lindahl, Anders
    Dept of Clinical Chemistry/Transfusion Medicine, Sahlgrenska University Hospital, Sweden.
    Olsson, Björn
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Sartipy, Peter
    Cellartis, Gothenburg, Sweden .
    Expression of microRNAs and their target mRNAs in human stem cell-derived cardiomyocyte clusters and in heart tissue2011In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, no 10, p. 581-594Article in journal (Refereed)
    Abstract [en]

    Recent studies have shown that microRNAs (miRNAs) act as posttranscriptional regulators and that they play important roles during heart development and in cardiac function. Thus, they may provide new means of altering stem cell fate and differentiation processes. However, information about the correlation between global miRNA and mRNA expression in cardiomyocyte clusters (CMCs) derived from human embryonic stem cells (hESC) and in fetal and adult heart tissue is lacking. In the present study the global miRNA and mRNA expression in hESC-derived CMCs and in fetal and adult heart tissue was investigated in parallel using microarrays. Target genes for the differentially expressed miRNAs were predicted using computational methods, and the concordance in miRNA expression and mRNA levels of potential target genes was determined across the experimental samples. The biology of the predicted target genes was further explored regarding their molecular functions and involvement in known regulatory pathways. A clear correlation between the global miRNA expression and corresponding target mRNA expression was observed. Using three different sources of cardiac tissue-like samples, we defined the similarities between in vitro hESC-derived CMCs and their in vivo counterparts. The results are in line with previously reported observations that miRNAs repress mRNA expression and additionally identify a number of novel miRNAs with potential important roles in human cardiac tissue. The concordant miRNA expression pattern observed among all the cardiac tissue-like samples analyzed here provide a starting point for future ambitious studies aiming towards assessment of the functional roles of specific miRNAs during cardiomyocyte differentiation.

  • 38.
    Synnergren, Jane
    et al.
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Vukusic, Kristina
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Dönnes, Pierre
    SciCross AB, Sweden.
    Jonsson, Marianne
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Lindahl, Anders
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Dellgren, Göran
    Department of Cardiothoracic Surgery, Sahlgrenska University Hospital Gothenburg, Sweden and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Jeppsson, Anders
    Department of Cardiothoracic Surgery, Sahlgrenska University Hospital Gothenburg, Sweden and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Asp, Julia
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden / Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Transcriptional sex and regional differences in paired human atrial and ventricular cardiac biopsies collected in vivo2020In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 52, no 2, p. 110-120Article in journal (Refereed)
    Abstract [en]

    Transcriptional studies of the human heart provide insight into physiological and pathophysiological mechanisms, essential for understanding the fundamental mechanisms of normal cardiac function and how they are altered by disease. To improve the understanding of why men and women may respond differently to the same therapeutic treatment it is crucial to learn more about sex-specific transcriptional differences. In this study the transcriptome of right atrium and left ventricle was compared across sex and regional location. Paired biopsies from five male and five female patients undergoing aortic valve replacement or coronary artery bypass grafting were included. Gene expression analysis identified 620 differentially expressed transcripts in atrial and ventricular tissue in men and 471 differentially expressed transcripts in women. In total 339 of these transcripts overlapped across sex but notably, 281 were unique in the male tissue and 162 in the female tissue, displaying marked sex differences in the transcriptional machinery. The transcriptional activity was significantly higher in atrias than in ventricles as 70% of the differentially expressed genes were upregulated in the atrial tissue. Furthermore, pathway- and functional annotation analyses performed on the differentially expressed genes showed enrichment for a more heterogeneous composition of biological processes in atrial compared with the ventricular tissue, and a dominance of differentially expressed genes associated with infection disease was observed. The results reported here provide increased insights about transcriptional differences between the cardiac atrium and ventricle but also reveal transcriptional differences in the human heart that can be attributed to sex.

  • 39.
    Thelander, Tilia
    University of Skövde, School of Health and Education.
    TNF-α gene polymorphism (-308G/A) in patients with obstructive sleep apnoea in a swedish population2019Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Obstructive sleep apnoea (OSA) is a prevalent breathing disorder that decreases the quality of life, and may lead to severe comorbidities. The complex genetic components of OSA pathogenesis advocates for genetic association studies to understand the underlying mechanisms. The tumor necrosis factor  (TNF-α -308G/A promoter polymorphism has been associated with OSA susceptibility in several populations, however this relationship has not been studied in the Swedish population. The aim of this study was to assess the genotype- and allele frequencies of TNF-α -308G/A polymorphism in a Swedish OSA cohort, and look for potential associations with clinical parameters related to OSA.

    Genomic DNA samples (n=326) from the Swedish RICCADSA cohort was genotyped with PCR-RFLP. PCR fragments were digested with the restriction enzyme NcoI and analysed in an automated Fragment Analyzer. The results indicated no association between the TNF-α -308G/A polymorphism and OSA susceptibility in this cohort, and no association between genotypes or allele carriage regarding severity, BMI distribution, circulatory TNF-α or comorbidities was found.  

    The results were potentially obscured by the subjects also having coronary artery disease (CAD), which may involve similar mechanisms as OSA. The cohort did not include samples from a matched healthy Swedish control population, meaning that the results may not reflect the actual relationship between TNF-α -308G/A polymorphism and OSA. In future work, inclusion of genotypes and clinical data from a matched healthy control group are required to investigate the potential relationship between the TNF-α -308G/A polymorphism and OSA in the Swedish population.

  • 40.
    Tilevik, Diana
    et al.
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Fagerlind, Magnus
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Tilevik, Andreas
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Ljungström, Lars
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Johansson, Markus
    1928 Diagnostics, Arvid Hedvalls backe, Gothenburg, Sweden.
    Enroth, Helena
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Molecular Microbiology, Laboratory Medicine, Unilabs AB, Skaraborg Hospital, Skövde.
    Sequence-based genotyping of extra-intestinal pathogenic Escherichia coli isolates from patients with suspected community-onset sepsis, Sweden2022In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 173, no Part A, article id 105836Article in journal (Refereed)
    Abstract [en]

    Extra-intestinal pathogenic Escherichia coli (ExPEC) strains are responsible for a large number of human infections globally. The management of infections caused by ExPEC has been complicated by the emergence of antimicrobial resistance, most importantly the increasing recognition of isolates producing extended-spectrum β-lactamases (ESBL). Herein, we used whole-genome sequencing (WGS) on ExPEC isolates for a comprehensive genotypic characterization. Twenty-one ExPEC isolates, nine with and 12 without ESBL-production, from 16 patients with suspected sepsis were sequenced on an Illumina MiSeq platform. Analysis of WGS data was performed with widely used bioinformatics software and tools for genotypic characterization of the isolates. A higher number of plasmids, virulence and resistance genes were observed in the ESBL-producing isolates than the non-ESBL-producing, although not statistically significant due to the low sample size. All nine ESBL-producing ExPEC isolates presented with at least one bla gene, as did three of the 12 without ESBL-production. Multi-locus sequence typing analysis revealed a diversity of sequence types whereas phylogroup A prevailed among isolates both with and without ESBL-production. In conclusion, this limited study shows that analysis of WGS data can be used for genotypic characterization of ExPEC isolates to obtain in-depth information of clinical relevance.

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  • 41.
    Visuttijai, Kittichate
    et al.
    University of Gothenburg, Göteborg, Sweden.
    Ejeskär, Katarina
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Behboudi, Afrouz
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Analyses of protein expression of PI 3-kinase/AKT signaling in response to altered expression of motor protein MYO1C2015In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75, no 15 Supplement, article id 2166Article in journal (Refereed)
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