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  • 1. Andersson, L
    et al.
    Petersen, G
    Johnson, P
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    A web tool for finding gene candidates associated with experimentally induced arthritis in rat2005Inngår i: Arthritis Research & Therapy , E-ISSN 1478-6362, Vol. 7, nr 3, s. R485-R492Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rat models are frequently used for finding genes contributing to the arthritis phenotype. In most studies, however, limitations in the number of animals result in a low resolution. As a result, the linkage between the autoimmune experimental arthritis phenotype and the genomic region, that is, the quantitative trait locus, can cover several hundred genes. The purpose of this work was to facilitate the search for candidate genes in such regions by introducing a web tool called Candidate Gene Capture (CGC) that takes advantage of free text data on gene function. The CGC tool was developed by combining genomic regions in the rat, associated with the autoimmune experimental arthritis phenotype, with rat/human gene homology data, and with descriptions of phenotypic gene effects and selected keywords. Each keyword was assigned a value, which was used for ranking genes based on their description of phenotypic gene effects. The application was implemented as a web-based tool and made public at http://ratmap.org/cgc. The CGC application ranks gene candidates for 37 rat genomic regions associated with autoimmune experimental arthritis phenotypes. To evaluate the CGC tool, the gene ranking in four regions was compared with an independent manual evaluation. In these sample tests, there was a full agreement between the manual ranking and the CGC ranking for the four highest-ranked genes in each test, except for one single gene. This indicates that the CGC tool creates a ranking very similar to that made by human inspection. The exceptional gene, which was ranked as a gene candidate by the CGC tool but not in the manual evaluation, was found to be closely associated with rheumatoid arthritis in additional literature studies. Genes ranked by the CGC tools as less likely gene candidates, as well as genes ranked low, were generally rated in a similar manner to those done manually. Thus, to find genes contributing to experimentally induced arthritis, we consider the CGC application to be a helpful tool in facilitating the evaluation of large amounts of textual information.

  • 2. Andersson, L
    et al.
    Petersen, G
    Johnson, P
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Finding genes contributing to the arthirits phenotype by comparing rat and human genome data2004Inngår i: Health Informatics Journal, ISSN 1460-4582, E-ISSN 1741-2811, Vol. 10, nr 1, s. 71-75Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Published quantitative trait locus (QTL) data, as well as all known rat genes and DNA markers, have since 1993 been collected and made easily accessible at the rat genome database, RatMap. The objective of the present study is to fully integrate available data concerning rat models with human genome information. The final goal of this process is to make results from any rat model experiment directly applicable to humans. The overall goal of this work is to create an automatic system which, for any given rat chromosomal region associated with a QTL, will characterize both mapped rat genes and all putative homologous human genes in that region. This article reports the use of the web application to find human gene candidates contributing to an arthritis phenotype.

  • 3. Andersson, L
    et al.
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Candidate Gene Capture (CGC): a Tool for Selecting Potentially2007Konferansepaper (Annet vitenskapelig)
  • 4. Andersson, L
    et al.
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Distribution of candidate genes for experimentally induced arthritis in rats2010Inngår i: BMC Genomics, E-ISSN 1471-2164, Vol. 11, nr 146Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Rat models are frequently used to link genomic regions to experimentally induced arthritis in quantitative trait locus (QTL) analyses. To facilitate the search for candidate genes within such regions, we have previously developed an application (CGC) that uses weighted keywords to rank genes based on their descriptive text. In this study, CGC is used for analyzing the localization of candidate genes from two viewpoints: distribution over the rat genome and functional connections between arthritis QTLs. Methods: To investigate if candidate genes identified by CGC are more likely to be found inside QTLs, we ranked 2403 genes genome wide in rat. The number of genes within different ranges of CGC scores localized inside and outside QTLs was then calculated. Furthermore, we investigated if candidate genes within certain QTLs share similar functions, and if these functions could be connected to genes within other QTLs. Based on references between genes in OMIM, we created connections between genes in QTLs identified in two distinct rat crosses. In this way, QTL pairs with one QTL from each cross that share an unexpectedly high number of gene connections were identified. The genes that were found to connect a pair of QTLs were then functionally analysed using a publicly available classification tool. Results: Out of the 2403 genes ranked by the CGC application, 1160 were localized within QTL regions. No difference was observed between highly and lowly rated genes. Hence, highly rated candidate genes for arthritis seem to be distributed randomly inside and outside QTLs. Furthermore, we found five pairs of QTLs that shared a significantly high number of interconnected genes. When functionally analyzed, most genes connecting two QTLs could be included in a single functional cluster. Thus, the functional connections between these genes could very well be involved in the development of an arthritis phenotype. Conclusions: From the genome wide CGC search, we conclude that candidate genes for arthritis in rat are randomly distributed between QTL and non-QTL regions. We do however find certain pairs of QTLs that share a large number of functionally connected candidate genes, suggesting that these QTLs contain a number of genes involved in similar functions contributing to the arthritis phenotype.

  • 5. Andersson, Lars
    et al.
    Petersen, Greta
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Ranking candidate genes in rat models of type 2 diabetes2009Inngår i: Theoretical Biology and Medical Modelling, E-ISSN 1742-4682, Vol. 6, nr 12Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Rat models are frequently used to find genomic regions that contribute to complex diseases, so called quantitative trait loci (QTLs). In general, the genomic regions found to be associated with a quantitative trait are rather large, covering hundreds of genes. To help selecting appropriate candidate genes from QTLs associated with type 2 diabetes models in rat, we have developed a web tool called Candidate Gene Capture (CGC), specifically adopted for this disorder. Methods CGC combines diabetes-related genomic regions in rat with rat/human homology data, textual descriptions of gene effects and an array of 789 keywords. Each keyword is assigned values that reflect its co-occurrence with 24 different reference terms describing sub-phenotypes of type 2 diabetes (for example "insulin resistance"). The genes are then ranked based on the occurrences of keywords in the describing texts. Results CGC includes QTLs from type 2 diabetes models in rat. When comparing gene rankings from CGC based on one sub-phenotype, with manual gene ratings for four QTLs, very similar results were obtained. In total, 24 different sub-phenotypes are available as reference terms in the application and based on differences in gene ranking, they fall into separate clusters. Conclusion The very good agreement between the CGC gene ranking and the manual rating confirms that CGC is as a reliable tool for interpreting textual information. This, together with the possibility to select many different sub-phenotypes, makes CGC a versatile tool for finding candidate genes. CGC is publicly available at http://ratmap.org/CGC.

  • 6. Behboudi, A
    et al.
    Roshani, L
    Kost-Alimova, M
    Sjöstrand, E
    Montelius-Alatalo, K
    Röhme, D
    Klinga-Levan, K
    Ståhl, Fredrik
    Göteborg University.
    Detailed Chromosomal and Radiation Hybrid Mapping in the Proximal Part of the Rat Chromosome 10 and gene order Comparison with Mouse and Human2002Inngår i: Mammalian Genome, ISSN 0938-8990, E-ISSN 1432-1777, Vol. 13, nr 6, s. 302-309Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 7. Behboudi, A
    et al.
    Roshani, L
    Lundin, L
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Klinga-Levan, K
    Levan, G
    Functional significance of absence: The chromosomal segment harboring the Tp53 gene is missing in the T55 rat radiation hybrid mapping panel2002Inngår i: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 79, nr 6, s. 844-848Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 8. Behboudi, A
    et al.
    Sjöstrand, E
    Gómez-Fabre, P
    Sjöling, Å
    Taib, Z
    Klinga-Levan, K
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Levan, G
    Evolutionary aspects of the genomic organization in rat chromosome 102002Inngår i: Cytogenetic and Genome Research, ISSN 1424-8581, E-ISSN 1424-859X, Vol. 96, nr 1-4, s. 52-59Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 9. Block, K
    et al.
    Alatalo, M
    Ståhl, Fredrik
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Ising, G
    Characterization of a minichromosome derived from the transposing element TE1 in Drosophila melanogaster1991Inngår i: Hereditas, Wiley-Blackwell Publishing, Inc. , 1991, s. 82-83Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The transposing element TEI contains the structural genes white and roughest from the Drosophilr X-chromosome. These genes are flanked by FB-elements, which are responsible for the mobility. At one occasion the TE, probably together with an adjacent segment in chromosome 2. has formed a minichromosome. This chromosome contains both the structural genes, the FB-elements,some centromeric and/or telomeric heterochromatin. It probably has a centromere as well, as it is transferred to the offspring at a high rate. From this minichromosome a smaller one has originated, probably through the loss of the region from chromosome 2 and some heterochromatin. This smaller minichromosome has been characterized in the following way: 1. Size determination hy pulsed field gel electrophoresis. -The chromosome turned out to be little more than one megabase. 2. y-irradiation of DNA from the minichromosome. ~ The aim of this experiment is to find out if the chromosome is circular or linear. A radiation dose which causes one break within a circle ought to accumulate DNA of the same size as the minichromosome. In this case no accumulation occurred and thus the chromosome is probably linear. 3. Cloning of sequences from the minichromosome. ~ A low melting agarose gel was run and a fragment was cut out from a region which contained DNA fragments of the same size as the minichromosome. The DNA was cut simultaneously by EcoR I and Pst I and ligated into the vector pBS containing T7 and T3 primers. The ligated DNA was amplified by the PCR method, which rendered several fragments of varying size. These fragments were ligated into the vector pCR1000TM. Positive clones are being analysed at present. With these clones we intend to construct a map of the minichromosome.

  • 10. Block, K
    et al.
    Ising, G
    Ståhl, Fredrik
    Minichromosomes in Drosophila melanogaster derived from the transposing element TE11990Inngår i: Chromosoma, ISSN 0009-5915, E-ISSN 1432-0886, Vol. 99, nr 5, s. 336-343Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A minichromosome has originated from the transposing element TE1. This autonomously replicating chromosome contains the structural genes white and roughest, from the Drosophila X chromosome. It arose within a stock carrying TE1 at 45F on chromosome 2. In addition to the w and rst genes, the minichromosome may carry section 45C-45F from chromosome 2. It is inherited by 33%-47% of the offspring. By this criterion it carries a centromere, although the origin of the centromere is unknown. From this minichromosome a still smaller one has originated, probably through the loss of all material from chromosome 2 together with some heterochromatin. At the same time a duplication of white and roughest could have taken place. This chromosome has a strange morphology and is more frequently lost in meiosis than the larger one, but is still transmitted to about 29%-37% of the progeny of one parent heterozygous for the minichromosome. In both cases the flies have variegated eyes, probably as a result of position-effect variegation. The variegation pattern is influenced by factors in the X chromosome. The size of the smaller minichromosome is little more than 1 Mb as determined by pulsed field gel electrophoresis.

  • 11.
    Cruz, Maria Araceli Diaz
    et al.
    Research School of Health and Welfare, School of Health and Welfare, University of Jönköping, Jönköping, Sweden.
    Ulfenborg, Benjamin
    Department of Biology and Bioinformatics, School of Bioscience, University of Skövde, Skövde, Sweden.
    Blomstrand, Peter
    Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, Jönköping, Sweden; Department of Clinical Physiology, County Hospital Ryhov, Jönköping, Sweden; Unit of Cardiovascular Sciences, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Faresjö, Maria
    Department of Biology and Biology Engineering, Chalmers University of Technology, Gothenburg, Sweden.
    Ståhl, Fredrik
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Karlsson, Sandra
    Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, Jönköping, Sweden.
    Characterization of methylation patterns associated with lifestyle factors and vitamin D supplementation in a healthy elderly cohort from Southwest Sweden2022Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikkel-id 12670Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Numerous studies have shown that lifestyle factors, such as regular physical activity and vitamin D intake, may remarkably improve overall health and mental wellbeing. This is especially important in older adults whose vitamin D deficiency occurs with a high prevalence. This study aimed to examine the influence of lifestyle and vitamin D on global DNA methylation patterns in an elderly cohort in Southwest of Sweden. We also sought to examine the methylation levels of specific genes involved in vitamin D's molecular and metabolic activated pathways. We performed a genome wide methylation analysis, using Illumina Infinium DNA Methylation EPIC 850kBeadChip array, on 277 healthy individuals from Southwest Sweden at the age of 70–95. The study participants also answered queries on lifestyle, vitamin intake, heart medication, and estimated health. Vitamin D intake did not in general affect methylation patterns, which is in concert with other studies. However, when comparing the group of individuals taking vitamin supplements, including vitamin D, with those not taking supplements, a difference in methylation in the solute carrier family 25 (SCL25A24) gene was found. This confirms a previous finding, where changes in expression of SLC25A24 were associated with vitamin D treatment in human monocytes. The combination of vitamin D intake and high physical activity increased methylation of genes linked to regulation of vitamin D receptor pathway, the Wnt pathway and general cancer processes. To our knowledge, this is the first study detecting epigenetic markers associated with the combined effects of vitamin D supplementation and high physical activity. These results deserve to be further investigated in an extended, interventional study cohort, where also the levels of 25(OH)D3 can be monitored.

    Fulltekst (pdf)
    fulltext
  • 12. Ekendahl, S
    et al.
    Arlinger, J
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Pedersen, K
    Carbon transformation in deep granitic groundwater by attached bacterial populations characterized with 16S -rRNA gene sequenccing technique and scanning electron microscopy1993Rapport (Annet vitenskapelig)
  • 13. Ekendahl, S
    et al.
    Arlinger, J
    Ståhl, Fredrik
    Pedersen, K
    Characterization of attached bacterial populations in deep granitic groundwaters from the deep chrystalline bedrock of the Stripa research mine by 16S rRNA gene sequencing and scanning electron microscopy1994Inngår i: Microbiology, ISSN 1350-0872, E-ISSN 1465-2080, Vol. 140, s. 1575-1583Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This paper presents the molecular characterization of attached bacterial populations growing in slowly flowing artesian groundwater from deep crystalline bed-rock of the Stripa mine, south central Sweden. Bacteria grew on glass slides in laminar flow reactors connected to the anoxic groundwater flowing up through tubing from two levels of a borehole, 812-820 m and 970-1240 m. The glass slides were collected, the bacterial DNA was extracted and the 16S rRNA genes were amplified by PCR using primers matching universally conserved positions 519-536 and 1392-1405. The resulting PCR fragments were subsequently cloned and sequenced. The sequences were compared with each other and with 16S rRNA gene sequences in the EMBL database. Three major groups of bacteria were found. Signature bases placed the clones in the appropriate systematic groups. All belonged to the proteobacterial groups beta and gamma. One group was found only at the 812-820 m level, where it constituted 63% of the sequenced clones, whereas the second group existed almost exclusively at the 970-1240 m level, where it constituted 83% of the sequenced clones. The third group was equally distributed between the levels. A few other bacteria were also found. None of the 16S rRNA genes from the dominant bacteria showed more than 88% similarity to any of the others, and none of them resembled anything in the database by more than 96%. Temperature did not seem to have any effect on species composition at the deeper level. SEM images showed rods appearing in microcolonies. The conditions at the levels differ in pH, temperature, redox and flow rate, and in content of sulphate, iron and sulphide. The presence of one dominant species in the laminar-flow reactors at each level indicates that the environments might have offered restrictive physical or physiological conditions difficult to adapt to.

  • 14.
    Gillsjö, Chatarina
    et al.
    School of Health Sciences, University of Skövde, Skövde, Sweden.
    Sandra, Karlsson
    Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, Jönköping, Sweden.
    Ståhl, Fredrik
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Eriksson, Irene
    School of Health Sciences, University of Skövde, Skövde, Sweden.
    Lifestyle's influence on community-dwelling older adults' health: A mixed-methods study design2021Inngår i: Contemporary Clinical Trials Communication, ISSN 2451-8654, Vol. 21, s. 1-4, artikkel-id 100687Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Aging often involves health problems and difficulties, such as physical and psychological impairments, isolation, and loneliness, causing social and existential consequences. Studies have explored aging from different perspectives. However, few studies have examined healthy older adults’ genetic backgrounds, lifestyles, and meaning in life separately or in combination. This study aims to describe how healthy older adults experience aging, health, lifestyles, and meaning in life and explore potential genetic correlations.

    Methods and Design:The project will comprise three main parts: a quantitative section featuring the development and testing of a lifestyle questionnaire, a quantitative genetic analysis, and a qualitative interview study. Participants will be community-dwelling, healthy, older adults between 70 and 95 years of age. A sample size of 800 older adults will be invited to participate in seminars in collaboration with the national Swedish association Active Seniors. Data will be collected through lifestyle questionnaire, DNA extracted from saliva samples, and interviews. Based on questionnaire responses, profile groups will be created and compared statistically with variations in genetic backgrounds, providing the basis for recruiting participants to the qualitative interviews.

    Discussion: This study’s expected outcome will be to gain knowledge about variations in genetic backgrounds correlated with individual experiences regarding aging, health, and meaning in life. This knowledge can improve the understanding of motivations for healthy lifestyle changes. The results can reveal potential implications for individual prerequisites to healthy aging and how health-promoting aging and lifestyle counseling can be adjusted to meet individual needs.

    Fulltekst (pdf)
    fulltext
  • 15. Gomez-Fabre, PM
    et al.
    Helou, K
    Klinga-Levan, K
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    A rat prediction map2001Inngår i: Journal of Molecular Medicine, Springer , 2001, s. 6-Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The rat and mouse had a common ancestor 15-40 Myr ago, and although substantial chromosomal rearrangements have occurred since they diverged, there is still a high degree of similarity in gene organization in the two genomes. Taking advantage of this similarity, mapping information can be transferred between the two genomes and prediction of positions for hitherto unmapped genes can be made with a high degree of accuracy. In this work, we have put together available information for 916 orthologous rat and mouse gene pairs and, with very few exceptions, all of the gene pairs fell into 52 distinct chromosomal segments (sex chromosomes not included). Most of these segments were confirmed by mouse-on-rat heterologous painting (zoo-FISH) and they were used to make up the backbone of a rat-mouse comparative map. This comparative map was used as a framework for making a rat-mouse prediction map. Predictions for the rat genome were made in two ways. Firstly, the relative position for each orthologous gene pair that cannot be deduced from rat gene data only was suggested from mouse gene data. Secondly, the tentative position in rat of approximately 5100 genes was inferred from the mouse. Thus, this comparative map confers a six-fold increase in the number of gene localization's available for the rat. In addition, the comparative map offers an efficient tool for exchanging genome information between rat and mouse.

  • 16. Gómez-Fabre, PM
    et al.
    Helou, K
    Ståhl, Fredrik
    Predictions based on the rat-mouse comparative map provide mapping information on over 6,000 new rat genes2002Inngår i: Mammalian Genome, ISSN 0938-8990, E-ISSN 1432-1777, Vol. 13, nr 4, s. 189-193Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    For identification of ECS (``evolutionarily conserved segments'') between rat and mouse, 893 rat–mouse orthologous gene-pairs were brought together with zoo-FISH analysis. In total, 59 autosomal ECS and 4 X-chromosomal ones were detected. Combining FISH and zoo-FISH data, the segments were anchored on the rat chromosomes, providing an improved comparative map between the two species. Since chromosomal evolution is a slow process, it is reasonable to assume that the genome organization, including gene order, is essentially conserved within the ECS. In this way we assigned tentative subchromosomal map positions to 303 rat genes, for which no regional mapping information was available. Furthermore, the concept of prediction mapping was extended to unmapped rat homologs of genes, which in the mouse are situated inside or in the vicinity of an ECS. For a total of 6669 genes, we predicted a single rat chromosomal position, whereas for another 448 genes we could predict that they were located in one of two possible positions. Thus, our study has increased the number of genes for which there is positional mapping information in the rat almost fivefold.

  • 17. Hallbeck, L
    et al.
    Ståhl, Fredrik
    Pedersen, K
    Phylogeny and phenotypic characterization of the stalkforming and iron-oxidizing bacterium Gallionella Ferruginea1993Inngår i: Journal of General Microbiology, ISSN 0022-1287, Vol. 139, nr 7, s. 1531-1535Artikkel i tidsskrift (Fagfellevurdert)
  • 18. Helou, K
    et al.
    Lü, XC
    Montelius-Alatalo, K
    Ståhl, Fredrik
    Klinga-Levan, K
    Levan, G
    A dual-color FISH framework map for the characterization of the Sai1 tumor suppression region on rat chromosome 52000Inngår i: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 27, nr 4, s. 362-372Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The analysis of cell hybrids between malignant mouse hepatoma cells and normal rat fibroblasts has previously demonstrated the critical role of a deletion in rat chromosome 5 (RNO5) that was related to an anchorage independent phenotype. Those hybrids that were anchorage independent displayed loss of the entire RNO5 or an interstitial deletion in RNO5. These findings suggested that a putative tumor suppressor gene, Sai1 (suppression of anchorage independence 1), was located within the deleted region. To explore the molecular basis of the tumor suppressor activity of the Sai1 region, we analyzed the RNO5q23-q36 region with several genes and microsatellite markers that could be assigned to the region, as well as with new markers derived by representational difference analysis (RDA) or by microdissection. Dual-color FISH was used to construct a detailed physical map of the entire RNO5. These new data can be used to connect the physical and linkage maps in the rat, as well as to identify the details of the comparative map with other mammalian species including humans and mice. Using as FISH reagents genomic YAC, P1, or phage lambda clones corresponding to RNO5 markers, the order and unique positions of 18 markers could be established. The map provided a framework for the detailed characterization of the deletion found in anchorage independent hybrids. All markers within the bands RNO5q31.3-q35 were shown to be lost, including known cancer-related genes such as Ifna (5q32), Cdkn2a, -b (5q32), Jun (5q34), and Cdkn2c (5q35). However, the aberration in the deletion chromosome turned out to be more complex than originally thought in that we detected the presence of a paracentric inversion in addition to a deletion. The inversion led to the juxtaposition of the gene markers Tal2 (5q24.1) and Cd30lg (5q24.3). The framework map will provide the basis for the detailed physical YAC clone contig mapping of this region, and facilitate the identification and characterization of the Sai1 locus.

  • 19. Helou, K
    et al.
    Wallenius, V
    Qiu, Y
    Öhman, F
    Ståhl, Fredrik
    Klinga-Levan, K
    Kindblum, LG
    Mandahl, N
    Jansson, JO
    Levan, G
    Amplification and overexpression of the hepatocyte growth factor receptor (HGFR/MET) in rat DMBA sarcomas1999Inngår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 18, nr 21, s. 3226-3234Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the present study subcutaneous fibrosarcomas were induced by the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) in rats from F1 generation cross breedings of two different inbred strains. Comparative genomic hybridization (CGH) analysis, which allows detection of DNA sequence copy changes, was applied to one of the tumors and it was found that there were increased copy numbers of sequences at chromosome 4q12-q21 in this tumor. We have previously determined that the loci for the hepatocyte growth factor (Hgf) and hepatocyte growth factor receptor (Hgfr/Met), a protooncogene, are situated in this particular chromosome region. Using probes for the two genes in FISH (fluorescence in situ hybridization) and in Southern blots we found that the Hgfr/Met gene was amplified in five of the 19 sarcomas studied, and that the Hgf gene was coamplified in two of them. Northern and Western blots and tyrosine phosphorylation analysis showed that the HGF receptor was overexpressed and functional in all five tumors, as well as in two additional tumors. In summary, both amplification and overexpression of the Hgfr/Met gene was found in about 25% of DMBA-induced experimental rat sarcomas, and HGF receptor overexpression alone was seen in two additional tumors. Possibly this reflects an involvement in paracrine or autocrine stimulation of growth and invasiveness by HGF. Our finding could provide a rodent model system to increased knowledge about causality and therapy, which may be applicable to the sizeable fraction of human musculoskeletal tumors displaying MET overexpression.

  • 20. Helou, K
    et al.
    Waltentinsson, A
    Levan, G
    Ståhl, Fredrik
    Between rat and mouse zoo-FISH reveals 49 chromosomal segments that have been conserved in evolution2001Inngår i: Mammalian Genome, ISSN 0938-8990, E-ISSN 1432-1777, Vol. 10, nr 12, s. 765-771Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mouse single chromosome paints were applied to rat prophase/prometaphase chromosomes to detect homologous chromosome regions. The analysis revealed 49 rat chromosomal regions ranging in size from whole chromosomes down to small bands near the limit of detection with this method, which was estimated to be 2-3 Mb. When all the painted regions were taken into account, the whole rat genome was covered with mouse-homologous regions, with the exception of small segments near the centromeres and the short arms of Chromosomes (Chrs) 3, 11, 12, and 13. These regions were shown to contain high levels of rat-specific repetitive DNA. The number of conserved segments between rat and mouse detected by our high-resolution zoo-FISH method was significantly higher than that reported in previous studies.

  • 21. Karlsson, Sandra
    et al.
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Larsson, Dennis
    Molecular diagnostic markers in endometrial carcinoma: an overview2013Inngår i: Journal of Oncopathology, ISSN 2052-5931, Vol. 1, nr 2, s. 145-150Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Endometrial, ovarian, and cervical cancers are three of the most common malignancies of the female reproductive organs and the most common cause of gynecological cancer deaths in the Western world. Approximately 80% or more of endometrial cancers are low-grade, estrogen-dependent, endometrioid adenocarcinoma (type I), whereas 20% are high-grade endometrial carcinomas (type II) associated with poor prognosis. Although endometrial cancer is usually diagnosed at an early stage, still almost 20% of the patients present with advanced disease. Thus, there is a need for highly sensitive markers that can distinguish between high- and low-risk endometrial carcinoma. To date, however, there are no validated molecular markers for endometrial cancer. Recent genomic and proteomic-based anaes show great promise for the discovery of new and more useful biomarkers. In this review, we will discuss the currently reported biomarkers that hold potential as diagnostic tools for endometrial cancer.

  • 22. Klinga-Levan, K
    et al.
    Henricsson, U
    Ståhl, Fredrik
    Integrated linkage maps in the rat1998Inngår i: Transplantation Proceedings, Elsevier Inc. , 1998, s. 1544-1545Konferansepaper (Fagfellevurdert)
  • 23. Klinga-Levan, K
    et al.
    Levan, G
    Ståhl, Fredrik
    The rat gene map 19941995Rapport (Annet vitenskapelig)
  • 24. Klinga-Levan, K
    et al.
    Levan, G
    Ståhl, Fredrik
    Towards an integrated rat gene map1999Rapport (Annet vitenskapelig)
  • 25. Klinga-Levan, K
    et al.
    Levan, G
    Ståhl, Fredrik
    Szpirer, J
    Szpirer, C
    The rat gene map 19951995Rapport (Annet vitenskapelig)
  • 26. Klinga-Levan, K
    et al.
    Levan, G
    Ståhl, Fredrik
    Szpirer, J
    Szpirer, C
    The rat gene map 19961996Rapport (Annet vitenskapelig)
  • 27. Klinga-Levan, K
    et al.
    Ståhl, Fredrik
    Report on rat chromosome 51999Rapport (Annet vitenskapelig)
  • 28. Klinga-Levan, K
    et al.
    Ståhl, Fredrik
    Levan, G
    Report on rat chromosome 51997Rapport (Annet vitenskapelig)
  • 29. Larsson, Dennis
    et al.
    Adele, Jonas
    Bergsten, Niklas
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Karlsson, Sandra
    Membrane Initiated Effects of 1?,25-Dihydroxyvitamin D3 in Prostate Cancer Cells: Effects on AP1 and CREB Mediated Transcription2012Inngår i: Current Frontiers and Perspectives in Cell Biology / [ed] Stevo Najman, InTech , 2012, s. 153-162Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [sv]

    Vitamin D effekter på progression av cancer i prostata

    Fulltekst (pdf)
    FULLTEXT01
  • 30. Levan, G
    et al.
    Klinga-Levan, K
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Szpirer, C
    Recent advances in rat genomics1997Inngår i: Transplantation Proceedings, ISSN 0041-1345, E-ISSN 1873-2623, Vol. 29, nr 3, s. 1759-1760Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The rat has been the model organism of choice for many researchers, for example, in physiology, immunology, and behavior research. Unfortunately, rat genetics have been lagging behind (compared to the mouse), but in the last decade considerable progress has been made in the field of “rat genomics,” as will be briefly reviewed below.

  • 31. Levan, G
    et al.
    Martinsson, T
    Ståhl, Fredrik
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Tumorigenicity and c-myc amplification in SEWA tumour cells1986Konferansepaper (Fagfellevurdert)
  • 32. Levan, G
    et al.
    Sandberg, P
    Ståhl, Fredrik
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Dahllöf, B
    Martinsson, T
    Wettergren, Y
    Selective gene amplification in mammalian cells1984Inngår i: Hereditas, Wiley-Blackwell Publishing, Inc. , 1984, s. 278-Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Selective gene amplification in mammalian cells is now recognized as a common cellular response to selection in a number of different toxic drugs, such as methotrexate (MTX). coformycin, PALA, hydroxyurea (HU), vincristine (VCR). colcemid (COL) and actinomycin D (AMD). Recently, we have studied SEWA murine tumor cells in culture exhibiting the pleiotropic drug resistance (PDR) phenotype. Cells subjected to stepwise selection in AMD, VCR or COL all develop double minute chromosomes (DM), which are a cytogenetic expression of gene amplification. These lines overproduce a 21 K acidic soluble protein and show a high degree of cross resistance, which is typical for the PDR phenotype. Other workers have shown that cells with this phenotype exhibit a shift in membrane-bound glycoproteins from 90- 100 K to 150-170 K. Thus, it is likely that several genes are involved in the development of the PDR phenotype. We have isolated a fraction highly enriched in DM from an AMD-resistant SEWA subline. DNA was extracted from this fraction, and several DM-specific DNA-probes were developed. These probes were used to study independently derived SEWA sublines resistant to AMD, VCR, COL, MTX and HU. The results showed that the investigated amplified DNA-segments in AMD-, VCR-. and COL-resistant lines exhibited a high degree of sequence sequence homology, indicating that basically the same segment was amplified in the 3 inductions. In contrast. the amplified DNA-segments in MTX- and HU-resistant lines that do not show the PDR phenotype, displayed no sequence homology to the probes used.

  • 33. Levan, G
    et al.
    Ståhl, Fredrik
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Klinga-Levan, K
    Szpirer, C
    Report on rat chromosome 171997Rapport (Annet vitenskapelig)
  • 34. Levan, G
    et al.
    Ståhl, Fredrik
    [External].
    Klinga-Levan, K
    Szpirer, J
    Szpirer, C
    The rat gene map1998Inngår i: ILAR journal, ISSN 1084-2020, E-ISSN 1930-6180, Vol. 39, s. 132-137Artikkel i tidsskrift (Fagfellevurdert)
  • 35. Levan, G
    et al.
    Ståhl, Fredrik
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Wettergren, Y
    Gene amplification in the murine SEWA system1992Inngår i: Mutation Research (Letters), ISSN 0165-7992, Vol. 276, nr 3, s. 285-290Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Considerable work with DNA amplification has been carried out in the murine SEWA ascites tumor cell system. In SEWA cells there is 'spontaneous' amplification of the c-myc oncogene, and transitions between different cytogenetic expressions of gene amplification such as DM (double minutes), CM (C-bandless chromosomes) and HSR (homogeneously staining regions) of the amplified DNA have been recorded during serial in vivo transplantations. In SEWA cells it has also been shown that the c-myc-containing DM will he lost under in vitro conditions, but are rapidly recovered if the cells are reinjected into animals. Additional gene amplification has been superimposed on the c-myc amplification in SEWA cells by stepwise selection in vitro, leading to resistance to different drugs, such as methotrexate, actinomycin D, colcemid and vincristine. Cytogenetically, DNA amplification is multifaceted and, in addition to the structures mentioned, it may also take the form of CB (chromatin bodies), which have been shown to be the carriers of resistance genes in hybrids between multidrug-resistant SEWA cells and Chinese hamster CHO cells. In most instances, DM are noncentromeric and distributed by a 'hitch-hiking' mechanism at mitosis; in one colcemid-resistant SEWA line, however, we have shown that the DM carry active centromeres. The molecular mechanism behind DNA amplification appears to be complex. We have shown that in four independently derived multidrug-resistant SEWA sublines the amplicons resided on circular molecules which were about 2500 kb long and carried at least five genes, including the three mouse mdr genes. Within the circles the DNA was unrearranged compared to the organization of the DNA in sensitive cells.

  • 36. Levan, G
    et al.
    Szpirer, C
    Klinga-Levan, K
    Ståhl, Fredrik
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Report on rat chromosome 171999Rapport (Annet vitenskapelig)
  • 37. Martinsson, T
    et al.
    Levan, G
    Ståhl, Fredrik
    Chromosomal localization of amplified DNA sequences in mouse tumour cells1985Inngår i: Anticancer Research, International Institute of Anticancer Research , 1985, s. 630-Konferansepaper (Fagfellevurdert)
  • 38. Martinsson, T
    et al.
    Ståhl, Fredrik
    Pollwein, P
    Wenxel, A
    Levan, A
    Schwab, M et al
    Tumorigenicity of SEWA murine tumor cells correlates with degree of c-myc amplification1988Inngår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 3, nr 4, s. 437-441Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous studies have shown that cells of the SEWA mouse tumor contain amplified copies of the proto-oncogene c-myc in the aberrant chromosomal structures of double minutes (DMs), homogeneously staining regions (HSRs) and C-bandless chromosomes (CMs). DMs, and to a lesser degree CMs, tend to disappear from the cells grown in vitro and again reappear after transfer back in vivo, as if DNA amplification confers a growth advantage upon the tumor cells. We have now isolated five in vitro clones that exhibit different degrees of c-myc amplification. When we inoculated cells of the different clones into compatible hosts, we found that there was a positive correlation between degree of c-myc amplification, level of c-myc RNA, and tumorigenicity. Our results lend further support to the idea that gene amplification contributes to the higher malignant phenotype, and to progression of tumors.

  • 39. Nilsson, S
    et al.
    Helou, K
    Walentinsson, A
    Szpirer, C
    Nerman, O
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Rat-mouse and rat-human comparative maps based on gene homology and high resolution zoo-FISH2001Inngår i: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 74, nr 3, s. 287-298Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The laboratory rat, Rattus norvegicus, and the laboratory mouse, Mus musculus, are key animal models in biomedical research. A deeper understanding of the genetic interrelationsships between Homo sapiens and these two rodent species is desirable for extending the usefulness of the animal models. We present comprehensive rat–human and rat–mouse comparative maps, based on 1090 gene homology assignments available for rat genes. Radiation hybrid, FISH, and zoo-FISH mapping data have been integrated to produce comparative maps that are estimated to comprise 83–100% of the conserved regions between rat and mouse and 66–82% of the conserved regions between rat and human. The rat–mouse zoo-FISH analysis, supported by data for individual genes, revealed nine previously undetected conserved regions compared to earlier reports. Since there is almost complete genome coverage in the rat–mouse comparative map, we conclude that it is feasible to make accurate predictions of gene positions in the rat based on gene locations in the mouse.

  • 40. Petersen, G
    et al.
    Johnson, P
    Andersson, L
    Klinga-Levan, K
    Gomez-Fabre, P
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    RatMap: rat genome tools and data2005Inngår i: Nucleic Acids Research - Database Issue, ISSN 0305-1048, Vol. 33, nr 1 (suppl), s. 492-494Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB–Genetics at Göteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided.

  • 41. Petersen, Greta
    et al.
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    RGST: Rat Gene Symbol Tracker, a database for defining official rat gene symbols2008Inngår i: BMC Genomics, E-ISSN 1471-2164, Vol. 9, nr 29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The names of genes are central in describing their function and relationship. However, gene symbols are often a subject of controversy. In addition, the discovery of mammalian genes is now so rapid that a proper use of gene symbol nomenclature rules tends to be overlooked. This is currently the situation in the rat and there is a need for a cohesive and unifying overview of all rat gene symbols in use. Based on the experiences in rat gene symbol curation that we have gained from running the "Ratmap" rat genome database, we have now developed a database that unifies different rat gene naming attempts with the accepted rat gene symbol nomenclature rules. Description This paper presents a newly developed database known as RGST (Rat Gene Symbol Tracker). The database contains rat gene symbols from three major sources: the Rat Genome Database (RGD), Ensembl, and NCBI-Gene. All rat symbols are compared with official symbols from orthologous human genes as specified by the Human Gene Nomenclature Committee (HGNC). Based on the outcome of the comparisons, a rat gene symbol may be selected. Rat symbols that do not match a human ortholog undergo a strict procedure of comparisons between the different rat gene sources as well as with the Mouse Genome Database (MGD). For each rat gene this procedure results in an unambiguous gene designation. The designation is presented as a status level that accompanies every rat gene symbol suggested in the database. The status level describes both how a rat symbol was selected, and its validity. Conclusion This database fulfils the important need of unifying rat gene symbols into an automatic and cohesive nomenclature system. The RGST database is available directly from the RatMap home page: http://ratmap.org.

  • 42. Pravenec, M
    et al.
    Kren, V
    Hedrich, H
    Szpirer, C
    Levan, G
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    St.Lezin, E
    Report on rat chromosome 11999Rapport (Annet vitenskapelig)
  • 43.
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Amplification of DNA sequences in SEWA murine tumor cells and in their multidrug-resistant derivatives1991Doktoravhandling, monografi (Annet vitenskapelig)
  • 44.
    Ståhl, Fredrik
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    RATMAP report: Resources on the Net1999Rapport (Annet vitenskapelig)
  • 45.
    Ståhl, Fredrik
    et al.
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Klinga Levan, K
    Levan, G
    The RATMAP database1995Rapport (Annet vitenskapelig)
  • 46.
    Ståhl, Fredrik
    et al.
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Klinga-Levan, K
    Levan, G
    Szpirer, J
    Szpirer, C
    The rat gene map 1996: fall revision1996Rapport (Annet vitenskapelig)
  • 47.
    Ståhl, Fredrik
    et al.
    Högskolan i Borås, Institutionen för Vårdvetenskap.
    Klinga-Levan, K
    Olbe, R
    Levan, G
    Physical rat chromosome at RATMAP1998Rapport (Annet vitenskapelig)
  • 48.
    Ståhl, Fredrik
    et al.
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Levan, G
    RATMAP: achievements and future plans1996Rapport (Annet vitenskapelig)
  • 49.
    Ståhl, Fredrik
    et al.
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Levan, G
    RATMAP: enhanced functions and future projects1997Rapport (Annet vitenskapelig)
  • 50.
    Ståhl, Fredrik
    et al.
    Högskolan i Borås, Akademin för vård, arbetsliv och välfärd.
    Levan, G
    RATMAP: new developments1999Rapport (Annet vitenskapelig)
12 1 - 50 of 62
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