219 research outputs found
Construction of a phylogenetic tree for inbred strains of rat by arbitrarily primed polymerase chain reaction (AP-PCR).
No full textGenetic Control of Resistance to Hepatocarcinogenesis by the Mouse Hpcr3 Locus
No full textHepatology. 2008 Aug;48(2):617-23.
Genetic control of resistance to hepatocarcinogenesis by the mouse Hpcr3 locus.
Manenti G, Galvan A, Falvella FS, Pascale RM, Spada E, Milani S, Gonzalez Neira A, Feo F, Dragani TA.
Source
Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Abstract
The genome of the BALB/c mouse strain provides alleles that dominantly inhibit hepatocellular tumor development in F1 crosses with the highly hepatocarcinogenesis-susceptible C3H/He strain. Genome-wide linkage analysis using a 1536-single-nucleotide polymorphism array in a (C3H/He x BALB/c)F2 intercross population treated with urethane to induce hepatocellular tumor development revealed a locus with a major role in the resistance to hepatocarcinogenesis. This locus, designated hepatocarcinogen resistance 3 (Hpcr3) and mapping to central chromosome 15, showed a linkage at LOD score = 16.52 and accounted for 40% of the phenotypical variance. The BALB/c-derived allele at Hpcr3 reduced tumor-occupied area of the liver up to 25-fold, in a semidominant way. Additional minor loci were mapped to chromosomes 1, 10, and 18. A gene expression profile of normal adult mouse liver showed a significant association with susceptibility of BALB/c, C3H/He, and F1 mice to hepatocarcinogenesis and identified the genes expressed in the Hpcr3 locus region; moreover, this analysis implicated the E2F1 pathway in the modulation of the phenotype susceptibility to hepatocarcinogenesis. CONCLUSION: These findings, indicating the complex genetics of dominant resistance to hepatocarcinogenesis, represent a step toward the identification of the genes underlying this phenotype
Multiple isoforms and differential allelic expression of CHRNA5 in lung tissue and lung adenocarcinoma
No full textCHRNA5 gene expression variation may play a role in individual susceptibility to lung cancer. Analysis of CHRNA5 transcripts expressed in normal lung tissue detected the full-length transcript (isoform-1) and four splicing transcripts (isoform-2 to isoform- 5), derived from the recognition of other splice sites in exon 5. Isoforms-2, -3 and -4 were found by protein modeling to form a completely folded, potentially functional extracellular domain and were observed at the protein level, whereas isoform-5 lacked a consistent part of the distorted æ sandwich and was not seen at the protein level. Only isoform-1 appeared to encode a complete, functional subunit able to fulfill the ion channel function. We previously reported that CHRNA5 expression is associated with genetic polymorphisms at this locus and that three haplotypes in its promoter region show functional regulation in vitro. Analysis of differential allelic expression (DAE) of three single nucleotide polymorphisms (rs503464, rs55853698 and rs55781567) tagging the expression haplotypes of the CHRNA5 promoter indicated statistically significant DAE at rs55853698 and rs55781567, in both normal lung and lung adenocarcinoma. Overall, our findings provide evidence for the presence of multiple CHRNA5 messenger RNA (mRNA) isoforms that may modulate the multimeric nicotine receptor and cis-regulatory variations in the CHRNA5 locus that act in vivo in the control of CHRNA5 mRNA expression, in normal lung tissue and in lung adenocarcinoma.CHRNA5 gene expression variation may play a role in individual susceptibility to lung cancer. Analysis of CHRNA5 transcripts expressed in normal lung tissue detected the full-length transcript (isoform-1) and four splicing transcripts (isoform-2 to isoform- 5), derived from the recognition of other splice sites in exon 5. Isoforms-2, -3 and -4 were found by protein modeling to form a completely folded, potentially functional extracellular domain and were observed at the protein level, whereas isoform-5 lacked a consistent part of the distorted æ sandwich and was not seen at the protein level. Only isoform-1 appeared to encode a complete, functional subunit able to fulfill the ion channel function. We previously reported that CHRNA5 expression is associated with genetic polymorphisms at this locus and that three haplotypes in its promoter region show functional regulation in vitro. Analysis of differential allelic expression (DAE) of three single nucleotide polymorphisms (rs503464, rs55853698 and rs55781567) tagging the expression haplotypes of the CHRNA5 promoter indicated statistically significant DAE at rs55853698 and rs55781567, in both normal lung and lung adenocarcinoma. Overall, our findings provide evidence for the presence of multiple CHRNA5 messenger RNA (mRNA) isoforms that may modulate the multimeric nicotine receptor and cis-regulatory variations in the CHRNA5 locus that act in vivo in the control of CHRNA5 mRNA expression, in normal lung tissue and in lung adenocarcinoma. © The Author 2013. Published by Oxford University Press. All rights reserved
Genetic mapping of the mouse Rab7 gene and pseudogene and of the human RAB7 homolog.
No full textRab proteins are small GTP-ases localized to distinct membrane compartments in eukaryotic cells and regulating specific steps of intracellular vesicular membrane traffic. The Rab7 protein is localized to the late endosomal compartment and controls late steps of endocytosis. We have isolated, by library screening, the 5' region, including the promoter, of the mouse Rab7 gene and a Rab7 pseudogene. We have mapped, by genetic linkage analysis, the mouse Rab7 gene on Chromosome (Chr) 6 and the Rab7-ps1 pseudogene on Chr 9, where the Rab7 gene has been previously reported to map. By radiation hybrid mapping, we have located the human RAB7 gene on Chr 3, in a region homologous to the mouse Chr 6, where the Rab7 gene maps
Promoter polymorphisms and transcript levels of nicotinic receptor CHRNA5
No full textChromosomal locus 15q25, implicated in lung cancer risk and nicotine dependence, shows extensive linkage disequilibrium that complicates identification of causal variation. Cholinergic receptor nicotinic α5 (CHRNA5) has been identified as a lung cancer risk factor. We identified by sequence analysis three haplotypes (delTTC, insATC, and insTGG) in the 5′ promoter region and three at the 3′-untranslated region of CHRNA5. Linkage disequilibrium analysis of the 5′ variants showed that the insTGG haplotype is associated with three tightly linked risk alleles (nicotine dependence, lung cancer, and chronic obstructive pulmonary disease). The three CHRNA5 promoter haplotypes were statistically significantly associated with lung CHRNA5 transcript levels, determined by real-time polymerase chain reaction. In nontumor lung parenchyma from 68 patients who underwent lung lobectomy, the delTTC haplotype was associated with the highest CHRNA5 transcript levels (relative quantification units = 1.82), whereas the insTGG haplotype was associated with the lowest (0.88 units, Pdiff <. 001, Welch t test; all statistical tests were two-sided). Luciferase reporter assays in human lung cancer cell lines A549, H460, H520, and H596 also showed that the 5′ region haplotypes were statistically significantly associated with changes in CHRNA5 promoter activity, whereas the 3′-untranslated region variants were not. © 2010 The Author
Loss of heterozygosity at chromosome 11q in lung adenocarcinoma: identification of three independent regions
No full textWe examined the pattern of allelic loss in 76 adenocarcinomas of the lung using 14 highly informative microsatellite markers on the long arm of chromosome 11. Loss of heterozygosity was found in 48 of 76 tumors (63%). Three distinct regions of deletion were identified. The first region, the most centromeric, lies between markers D11S940 and CD3D: the second, delimited by markers D11S924 and D11S925, is estimated to be 4 Mb in length, and has never been previously described; a third, more telomeric region, the length of which is also estimated to be in the range of 4 Mb, is bracketed by loci D11S1345 and D11S1328. These findings suggest the presence of at least three tumor suppressor genes on the long arm of chromosome 11, and confirm the relevance of 11q22-24, a region frequently deleted in carcinomas of the breast, ovary, uterine, cervix, colon, and malignant melanoma in the pathogenesis of solid tumors. The characterization of minimal regions of loss could provide the basis for the identification and cloning of the critical genes
Cloning, chomosome mapping and funcional characterization of a human homologue of murine gtse-1(B99) gene
No full textUTILIZZO DI UN MEZZO ADATTATO AD UN PORTATORE DI MALATTIA DI PERTHES. RIPERCUSSIONI FUNZIONALI ERGOSPIROMETRICHE
No full textLoss of heterozygosity at 11q in lung adenocarcinoma: identification of three independent regions.
No full textCloning, chromosome mapping and functional characterization of a human homologue of murine Gtse-1 (B99) gene
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