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Sökning: WFRF:(Klinga K)

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1.
  • Helou, K, et al. (författare)
  • A dual-color FISH framework map for the characterization of the Sai1 tumor suppression region on rat chromosome 5
  • 2000
  • Ingår i: Genes, Chromosomes and Cancer. - : John Wiley & Sons, Inc.. - 1045-2257 .- 1098-2264. ; 27:4, s. 362-372
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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2.
  • Gomez-Fabre, PM, et al. (författare)
  • A rat prediction map
  • 2001
  • Ingår i: Journal of Molecular Medicine. - : Springer. ; , s. 6-
  • Konferensbidrag (refereegranskat)abstract
    • 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.
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3.
  • Helou, K, et al. (författare)
  • Amplification and overexpression of the hepatocyte growth factor receptor (HGFR/MET) in rat DMBA sarcomas
  • 1999
  • Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 18:21, s. 3226-3234
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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4.
  • Behboudi, A, et al. (författare)
  • Functional significance of absence : The chromosomal segment harboring the Tp53 gene is missing in the T55 rat radiation hybrid mapping panel
  • 2002
  • Ingår i: Genomics. - : Academic Press. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-848
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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6.
  • Klinga-Levan, K, et al. (författare)
  • Integrated linkage maps in the rat
  • 1998
  • Ingår i: Transplantation Proceedings. - : Elsevier Inc.. ; , s. 1544-1545
  • Konferensbidrag (refereegranskat)
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9.
  • Klinga-Levan, K, et al. (författare)
  • The rat gene map 1994
  • 1995
  • Rapport (övrigt vetenskapligt/konstnärligt)
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10.
  • Klinga-Levan, K, et al. (författare)
  • The rat gene map 1995
  • 1995
  • Rapport (övrigt vetenskapligt/konstnärligt)
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