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- Behboudi, Afrouz, 1967, et al.
(författare)
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Detailed chromosomal and radiation hybrid mapping in the proximal part of rat Chromosome 10 and gene order comparison with mouse and human.
- 2002
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Ingår i: Mammalian genome : official journal of the International Mammalian Genome Society. - : Springer Science and Business Media LLC. - 0938-8990 .- 1432-1777. ; 13:6, s. 302-9
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Behboudi, Afrouz, 1967, et al.
(författare)
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Evolutionary aspects of the genomic organization of rat chromosome 10.
- 2002
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Ingår i: Cytogenetic and genome research. - : S. Karger. - 1424-8581 .- 1424-859X. ; 96:1-4, s. 52-9
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Behboudi, Afrouz, 1967, et al.
(författare)
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High-density marker loss of heterozygosity analysis of rat chromosome 10 in endometrial adenocarcinoma.
- 2001
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Ingår i: Genes, chromosomes & cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 32:4, s. 330-41
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Behboudi, Afrouz, 1967, et al.
(författare)
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The functional significance of absence: the chromosomal segment harboring Tp53 is absent from the T55 rat radiation hybrid mapping panel.
- 2002
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-8
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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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- Enlund, Fredrik, 1968, et al.
(författare)
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Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.
- 2004
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Ingår i: Experimental cell research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 292:1, s. 21-8
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome translocations in neoplasia commonly result in fusion genes that may encode either novel fusion proteins or normal, but ectopically expressed proteins. Here we report the cloning of a novel fusion gene in a common type of salivary and bronchial gland tumor, mucoepidermoid carcinomas (MEC), as well as in benign Warthin's tumors (WATs). The fusion, which results from a t(11;19)(q21-22;p13) translocation, creates a chimeric gene in which exon 1 of a novel gene of unknown function, designated WAMTP1, is linked to exons 2-5 of the recently identified Mastermind-like Notch coactivator MAML2. In the fusion protein, the N-terminal basic domain of MAML2, which is required for binding to intracellular Notch (Notch ICD), is replaced by an unrelated N-terminal sequence from WAMTP1. Mutation analysis of the N-terminus of WAMTP1-MAML2 identified two regions of importance for nuclear localization (amino acids 11-20) and for colocalization with MAML2 and Notch1 ICD in nuclear granules (amino acids 21-42). Analyses of the Notch target genes HES5 and MASH1 in MEC tumors with and without the WAMTP1-MAML2 fusion revealed upregulation of HES5 and downregulation of MASH1 in fusion positive MECs compared to normal salivary gland tissue and MECs lacking the fusion. These findings suggest that altered Notch signaling plays an important role in the genesis of benign and malignant neoplasms of salivary and bronchial gland origin.
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| 8. |
- Sjöling, Åsa, et al.
(författare)
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Recurrent allelic imbalance at the rat Pten locus in DMBA-induced fibrosarcomas
- 2002
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Ingår i: Genes, Chromosomes and Cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 36:1, s. 70-79
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Tidskriftsartikel (refereegranskat)abstract
- The tumor-suppressor gene PTEN (phosphatase and tensin homolog) is frequently inactivated in different types of human tumors. Less is known about the involvement of the homologous gene Pten in animal model systems of cancer. By sequencing one of the introns of rat Pten, we found an informative intragenic PCR marker suitable for genetic studies. Through use of this marker, the position of Pten in the genetic linkage map was localized to the distal part of rat chromosome 1 (RNO1) by analysis of F2 progeny from an intercross between inbred strains BN and LE. Subsequently, 22 markers from this region (including the intragenic Pten marker) were used to study the occurrence of allelic imbalance in distal RNO1 in fibrosarcomas that had been induced by DMBA in F1(BN×LE) rats. The analysis revealed that allelic imbalance was common in the vicinity of Pten, and there was loss or reduction of one of the Pten alleles in more than 60% of the fibrosarcomas. DNA sequencing was preformed to investigate whether the Pten allele remaining in the tumors was inactivated by mutation. However, no mutations were detected in the genomic sequence of Pten exons 5 to 9 in any of the fibrosarcomas, and normal mRNA transcripts were expressed in all tumors. Thus, based on the targeted selection for loss of Pten observed in some of these tumors and the absence of inactivation of the remaining allele, we suggest that haploinsufficiency of Pten may be an important factor in rat DMBA-induced fibrosarcomas. © 2002 Wiley-Liss, Inc.
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