共查询到14条相似文献,搜索用时 0 毫秒
1.
Lung tumor cell DNA copy number alteration (CNA) was expected to display specific patterns such as a large-scale amplification
or deletion of chromosomal arms, as previously published data have reported. Peripheral blood mononuclear cell (PBMC) CNA
however, was expected to show normal variations in cancer patients as well as healthy individuals, and has thus been used
as normal control DNA samples in various published studies. We performed array CGH to measure and compare genetic changes
in terms of the CNA of PBMC samples as well as DNA isolated from tumor tissue samples, obtained from 24 non-small cell lung
cancer patients. Contradictory to expectations, our studies showed that the PBMC CNA also showed chromosomal variant regions.
The list included well-known tumor-associated NTRK1, FGF8, TP53, and TGFβ1 genes and potentially novel oncogenes such as THPO (3q27.1), JMJD1B, and EGR1 (5q31.2), which was investigated in this study. The results of this study highlighted the connection between PBMC and tumor
cell genomic DNA in lung cancer patients. However, the application of these studies to cancer prognosis may pose a challenge
due to the large amount of information contained in genetic predisposition and family history that has to be processed for
useful downstream clinical applications. 相似文献
2.
The combination of array-based comparative genomic hybridization (CGH) with fluorescence in situ hybridization utilizing custom-designed
bacterial artificial chromosome (BAC) probes applied to tissue microarrays represents a powerful compendium of techniques–greatly
enhancing the throughput of genomic analysis and subsequent target validation. Such approach can be automated at various levels
and allows managing large volume of targets and samples in a few experiments. As such, this approach facilitates discovery,
validation and implementation of findings in the process of identification of new diagnostic, prognostic and potentially therapeutic
molecular markers. 相似文献
3.
Exposure to genotoxic carcinogens in tobacco smoke is a major cause of lung cancer. However, the effect this has on DNA copy number and genomic stability during lung carcinogenesis is unclear. Here we used bacterial artificial chromosome array-based comparative genomic hybridization to examine the effect of NNK, a potent human lung carcinogen present in tobacco smoke, on the major genomic changes occurring during mouse lung adenocarcinogenesis. Observed were significantly more gross chromosomal changes in NNK-induced tumors compared with the spontaneous tumors. An average of 5.6 chromosomes were affected by large-scale changes in DNA copy number per NNK-induced tumor compared with only 2.0 in spontaneous lung tumors (p = 0.017). Further analysis showed that gains on chromosomes 6 and 8, and losses on chromosomes 11 and 14 were more common in NNK-induced tumors (p 相似文献
4.
Gene amplification profiling of esophageal squamous cell carcinomas by DNA array CGH 总被引:6,自引:0,他引:6
Ishizuka T Tanabe C Sakamoto H Aoyagi K Maekawa M Matsukura N Tokunaga A Tajiri T Yoshida T Terada M Sasaki H 《Biochemical and biophysical research communications》2002,296(1):152-155
Gene amplification is one of the basic mechanisms that lead to overexpression of oncogenes. DNA array comparative genomic hybridization (CGH) has great potential for comprehensive analysis of both a relative gene-copy number and altered chromosomal regions in cancers, which enables us to identify new amplified genes and unstable chromosomal loci. We examined the amplification status in 32 esophageal squamous cell carcinomas (ESCCs) and 13 ESCC cell lines on 51 frequently amplified loci in a variety of cancers by both DNA array CGH and Southern blot analyses. The 1p34 locus containing MYCL1, 2p24 (MYCN), 7p12 (EGFR), and 12q14 (MDM2) were amplified in one of the 32 cases (3%), and the 17q12 locus (ERBB2) and 8p11 (FGFR1) in two of the 32 cases (6%), while only the 11q13 locus (Cyclin D1, FGF4, and EMS1) was frequently amplified (28%, 9/32), demonstrating this locus to be a major target in ESCCs. One locus, 8q24 (c-MYC) was found to be amplified only in the cell lines. Eight out of 51 loci (15.7%) were found to be amplified in at least one of the 32 primary ESCCs or the 13 ESCC cell lines, suggesting that chromosomal loci frequently amplified in a type of human cancer may also be amplified in other types of cancers. This paper is the first report of an application of DNA array CGH to ESCCs. 相似文献
5.
K. Kaneko 《Population Ecology》2002,44(2):71-85
A mechanism of sympatric speciation is presented based on the interaction-induced developmental plasticity of phenotypes.
First, phenotypes of individuals with identical genotypes split into a few groups, according to instability in the developmental
dynamics that are triggered with the competitive interaction among individuals. Then, through mutational changes in the genes,
the phenotypic differences are fixed to genes, until the groups are completely separated in genotype as well as phenotype.
It is also demonstrated that the proposed theory leads to hybrid sterility under sexual recombination, and thus speciation
is completed in the sense of reproductive isolation. As a result of this postmating isolation, the mating preference evolves
later. When there are two alleles, the correlation between alleles is formed to consolidate speciation. When individuals are
located apart in space, different species are later segregated spatially, implying that the speciation so far regarded to
be allopatric may be a result of sympatric speciation. Relationships to previous theories, frequency-dependent selection,
reinforcement, Baldwin's effect, phenotypic plasticity, and resource competition are briefly discussed. Relevance of the results
to natural evolution is discussed, including punctuated equilibrium, incomplete penetrance in mutants, and the change in flexibility
in genotype–phenotype correspondence. Finally, we discuss how our theory is confirmed both in the field and in the laboratory,
in an experiment using Escherichia coli.
Received: January 30, 2002 / Accepted: May 13, 2002 相似文献
6.
Supernumerary marker chromosomes (SMC) are heterogeneous group of chromosomes which are reported in variable phenotypes. Approximately 70% originate from acrocentric chromosomes. Here we report a couple with recurrent miscarriages and a SMC originating from an acrocentric chromosome. The cytogenetic analysis of the husband revealed a karyotype of 47,XY+marker whereas the wife had a normal karyotype. Analysis of SMC with C-banding showed the presence of a big centromere in the center and silver staining showed prominent satellites on both sides of the marker. Apparently, microarray analysis revealed a 2.1 Mb duplication of 15q11.2 region but molecular cytogenetic analysis by fluorescence in situ hybridization (FISH) with whole chromosome paint (WCP) 15 showed that the SMC is not of chromosome 15 origin. Subsequently, FISH with centromere 22 identified the SMC to originate from chromosome 22 which was also confirmed by WCP 22. Additional dual FISH with centromere 22 and Acro-p-arm probes confirmed the centromere 22 and satellites on the SMC. Further fine mapping of the marker with Bacterial Artificial Chromosome (BAC) clones; two on chromosome 22 and four on chromosome 15 determined the marker to possess only centromere 22 sequences and that the duplication 15 exists directly on chromosome 15. In our study, we had identified and characterized a SMC showing inversion duplication 22(p11.1) combined with a direct tandem duplication of 15q11.2. The possible genotype–phenotype in relation with the two rearrangements is discussed. 相似文献
7.
Prenatal diagnosis of proximal partial trisomy 1q confirmed by comparative genomic hybridization array: Molecular cytogenetic analysis,fetal pathology and review of the literature 下载免费PDF全文
Stavros Sifakis Makarios Eleftheriades Dimitra Kappou Roberta Murru Anastasia Konstantinidou Sandro Orru Monika Ziegler Thomas Liehr Emmanouil Manolakos Ioannis Papoulidis 《Birth defects research. Part A, Clinical and molecular teratology》2014,100(4):284-293
8.
Chih-Ping Chen Po-Jen Cheng Shuenn-Dyh Chang Yi-Xuan Lee Jin-Chung Shih Schu-Rern Chern Peih-Shan Wu Jun-Wei Su Yu-Ting Chen Adam Hwa-Ming Hsieh Teresa Hsiao-Tien Chen Li-Feng Chen Wayseen Wang 《Gene》2013
We present perinatal findings and molecular cytogenetic characterization of a prenatally detected sacrococcygeal teratoma associated with mosaic r(21). This is the first report of mosaic r(21) presenting with a fetal sacrococcygeal teratoma. We discuss cytogenetic abnormalities associated with fetal sacrococcygeal teratomas. 相似文献
9.
Inherited Interstitial Duplications of Proximal 15q: Genotype-Phenotype Correlations 总被引:10,自引:1,他引:9 下载免费PDF全文
C.E. Browne N.R. Dennis E. Maher F.L. Long J.C. Nicholson J. Sillibourne J.C.K. Barber 《American journal of human genetics》1997,61(6):1342-1352
We present the cytogenetic, molecular cytogenetic, and molecular genetic results on 20 unrelated patients with an interstitial duplication of the proximal long arm of chromosome 15. Multiple probes showed that the Prader-Willi/Angelman critical region (PWACR) was included in the duplication in 4/20 patients, each ascertained with developmental delay. The duplication was also found in two affected but not in three unaffected sibs of one of these patients. All four probands had inherited their duplication from their mothers, three of whom were also affected. Two of the affected mothers also carried a maternally inherited duplication, whereas the duplication in the unaffected mother and in an unaffected grandmother was paternal in origin, raising the possibility of a parental-origin effect. The PWACR was not duplicated in the remaining 16 patients, of whom 4 were referred with developmental delay. In the 14 families for which parental samples were available, the duplication was inherited with equal frequency from a phenotypically normal parent, mother or father. Comparative genomic hybridization undertaken on two patients suggested that proximal 15q outside the PWACR was the origin of the duplicated material. The use of PWACR probes discriminates between a large group of duplications of no apparent clinical significance and a smaller group, in which a maternally derived PWACR duplication is consistently associated with developmental delay and speech difficulties but not with overt features of either Prader-Willi syndrome or Angelman syndrome. 相似文献
10.
Cheon MS Kim SH Ovod V Kopitar Jerala N Morgan JI Hatefi Y Ijuin T Takenawa T Lubec G 《Amino acids》2003,24(1-2):127-134
Summary. Down syndrome (DS) is the most frequent genetic disorder with mental retardation and caused by trisomy 21. Although the gene
dosage effect hypothesis has been proposed to explain the impact of extra chromosome 21 on the pathology of DS, a series of
evidence that challenge this hypothesis has been reported. The availability of the complete sequences of genes on chromosome
21 serves now as starting point to find functional information of the gene products, but information on gene products is limited
so far. We therefore evaluated expression levels of six proteins whose genes are encoded on chromosome 21 (synaptojanin-1,
chromosome 21 open reading frame 2, oligomycin sensitivity confering protein, peptide 19, cystatin B and adenosine deaminase
RNA-specific 2) in fetal cerebral cortex from DS and controls at 18–19 weeks of gestational age using Western blot analysis.
Synaptojanin-1 and C21orf2 were increased in DS, but others were comparable between DS and controls, suggesting that the DS
phenotype cannot be simply explained by gene dosage effects. We are systematically quantifying all proteins whose genes are
encoded on chromosome 21 in order to provide a better understanding of the pathobiochemistry of DS at the protein level. These
studies are of significance as they show for the first time protein levels that are carrying out specific function in human
fetal brain with DS.
Received August 12, 2002 Accepted September 12, 2002 Published online January 30, 2003
Authors' address: Prof. Dr. Gert Lubec, CChem, FRSC (UK) Department of Pediatrics, University of Vienna, Waehringer Guertel 18, A-1090 Vienna,
Austria, Fax: +43-1-40400-3194, E-mail: gert.lubec@akh-wien.ac.at
Abbreviations: ADAR2, adenosine deaminase RNA-specific 2; C21orf2, chromosome 21 open reading frame 2; DS, Down syndrome; NSE, neuron specific
enolase; OSCP, oligomycin sensitivity conferring protein; PEP-19, peptide 19 相似文献
11.
Ochsenbein F Neumann JM Guittet E van Heijenoort C 《Protein science : a publication of the Protein Society》2002,11(4):957-964
A spectral density model based on a truncated lorentzian distribution of correlation times is used to analyze the nanosecond time-scale dynamics of the partially unfolded domain 2 of annexin I from its (15)N NMR relaxation parameters measured at three magnetic field strengths. The use of a distribution of correlation times enables the characterization of the dynamical features of the NH bonds of the protein in terms of heterogeneity of dynamical states in the nanosecond range. The variation along the sequence of the two dynamical parameters introduced, namely the center and the width of the distribution, points out the different types of residual secondary structures present in the D2 domain. Moreover, it allows a physically sensible interpretation of the dynamical behavior of the different residual helices and of the non-native structures. Also, a striking correspondence is found between the parameters obtained using an extended Lipari and Szabo model and the parameters obtained using the distribution of correlation times. This result led us to propose a specific interpretation of the model-free order parameter for internal motions in the nanosecond range in the case of unfolded states. 相似文献
12.
Wagenführ K Pieper S Mackeldanz P Linscheid M Krüger DH Reuter M 《Journal of molecular biology》2007,366(1):93-102
The Type III restriction endonuclease EcoP15I forms a hetero-oligomeric enzyme complex that consists of two modification (Mod) subunits and two restriction (Res) subunits. Structural data on Type III restriction enzymes in general are lacking because of their remarkable size of more than 400 kDa and the laborious and low-yield protein purification procedures. We took advantage of the EcoP15I-overexpressing vector pQEP15 and affinity chromatography to generate a quantity of EcoP15I high enough for comprehensive proteolytic digestion studies and analyses of the proteolytic fragments by mass spectrometry. We show here that in the presence of specific DNA the entire Mod subunit is protected from trypsin digestion, whereas in the absence of DNA stable protein domains of the Mod subunit were not detected. In contrast, the Res subunit is comprised of two trypsin-resistant domains of approximately 77-79 kDa and 27-29 kDa, respectively. The cofactor ATP and the presence of DNA, either specific or unspecific, are important stabilizers of the Res subunit. The large N-terminal domain of Res contains numerous functional motifs that are predicted to be involved in ATP-binding and hydrolysis and/or DNA translocation. The C-terminal small domain harbours the catalytic center. Based on our data, we conclude that both structural Res domains are connected by a flexible linker region that spans 23 amino acid residues. To confirm this conclusion, we have investigated several EcoP15I enzyme mutants obtained by insertion mutagenesis in and around the predicted linker region within the Res subunit. All mutants tolerated the genetic manipulation and did not display loss of function or alteration of the DNA cleavage position. 相似文献
13.
Summary This paper reports a field study for the assessment of the variation in15N natural abundance method to estimate nitrogen fixation. For two successive years (1979 and 1980) at the same site, distribution
of the variable δ15N in populations of nodulating and non-nodulating soybeans (Glycine max) has been studied. In 1980, the population structure was studied in order to detect a neighbour effect which could explain
bimodal trend observed in the distribution. There was no evidence for such an effect. A sampling procedure is proposed: with
15 to 30 nodulating plants chosen randomly, a confidence interval of ±0.5δ can be obtained, while less than 10 non-nodulating
plants are sufficient to achieve a very good precision. Some other aspects are studied: effect of pooling plants which considerably
reduce the experimental work; the use of a non leguminous reference plant is possible. All our results show that fixing capacity
introduces major variability in the δ15N measured in the plants, while the absence of fixation leads to a homogenous population, so the percentage of fixed N can
be evaluated with a rather good precision. The higher the reference value, the better the accuracy of this evaluation, for
a given precision of a δ15N measurement. 相似文献
14.
We report on a 36-year-old infertile woman, presenting a premature ovarian failure with an otherwise normal female phenotype. Cytogenetic analyses showed the presence of a supernumerary marker chromosome, that was characterized by FISH (fluorescent in situ hybridization) and array CGH (comparative genomic hybridization). This marker chromosome was derived from chromosome 15, and contained only heterochromatic material. The Prader Willi/Angelman region was not present. No duplications of the 15q regions were detected by array CGH. Supernumerary markers of chromosome 15 have been reported in cases of infertility and amenorrhea, that is also described in cases with marker derived by other acrocentric chromosomes. The case here presented constitutes a further example that etiology of POF is not always associated with a defective gene, but in some cases oocytes atresia can be the consequence of the abnormal meiotic pairing of chromosomes. 相似文献