Proceedings: Report of the Committee on Genetic Markers. Gene markers for mapping the human genome.
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Antigens↗
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Results for “Marker gene”
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10q(q23 leads to qter) duplication: GOTs, HK1, and other gene markers.
Gene marker analyses have been carried out in a patient with 10q(q23 leads to qter) duplication. The observed elevation of red cell glutamic oxaloacetic transaminase activity is compatible with earlier somatic cell hybridization studies that mapped the locus to this region. Hexokinase-1 activity in the red cells was normal,which is consistent with its prior assignment to the unaffected part of chromosome 10(10pter leads to q23).
Adult↗
Consensus promoter identification in the human genome utilizing expressed gene markers and gene modeling.
Deciphering the human genome includes locating the promoters that initiate transcription and identifying the exons of genes. Many promoter prediction programs have been proposed, but when they are applied to extended regions of the genome, most of their predictions are false-positives. The extensive collection of gene transcript sequences is an important new source of information, which has not been used previously in promoter predictions. Our approach is to enhance the specificity of predictions by restricting the genomic regions that are searched using gene transcript alignments as anchors in the genome for gene modeling. We developed a consensus promoter prediction method combining previously developed algorithms with the GENSCAN gene modeling program. Our method, CONPRO (CONsensus PROmoter), identifies promoters with very high confidence, and the predicted promoters are guaranteed to be associated with genes. On our test data set, the method correctly detects promoters for approximately half of all human genes (37%-71%), and most predictions are true promoters (85%-90%). Applying our method to the human genome and human genes from the Unigene data set, we find the promoters for 13,744 genes. Of these, 6440 are genes with a functionally cloned mRNA, and 7304 are novel genes for which only expressed sequence tags (ESTs) are available. Candidate promoters for many novel genes will be a useful resource in elucidating complex biological response mechanisms.
5' Untranslated Regions↗
Human transferrin receptor gene as a marker gene for MR imaging.
PURPOSE: To quantitate and characterize the expression of an engineered human transferrin receptor (ETR) as a marker gene by using magnetic resonance (MR) imaging. MATERIALS AND METHODS: Rat gliosarcoma 9L cells stably expressing ETR (ETR+) were used, with nontransfected (ETR-) cells serving as controls. A conjugate of transferrin and monocrystalline iron oxide (Tf-MION) nanoparticles was synthesized to probe for the activity of ETR. Accumulation of Tf-MION was examined by using cell internalization in culture and MR (n = 6) and nuclear (n = 4) imaging in a mouse model with ETR+ and ETR- tumors implanted in the opposite flanks. Autoradiographic and histopathologic results were correlated with MR findings. RESULTS: Tf-MION was internalized by ETR+ cells at 37 degrees C but not at 4 degrees C. Rhodamine-labeled Tf-MION and fluorescein-labeled antibody to ETR colocalized in small vesicle-like structures in the cytoplasm. Both findings were consistent with accumulation by the receptor-mediated endocytosis mechanism of ETR. Compared with ETR- tumors, ETR+ tumors accumulated more Tf-MION and had higher signal intensity on T1-weighted MR images and lower signal intensity on T2-weighted images. Autoradiographic findings showed a spatial correlation between MR signal intensity and TF-MION accumulation. CONCLUSION: ETR+ tumors internalize the MR imaging probe through the action of transferrin receptor in amounts that can be detected with MR imaging.
Animals↗
The contribution of marker gene studies to hemopoietic stem cell therapies.
Although the transfer of "therapeutic" genes into hemopoietic stem cells (HSC) offers many opportunities to treat a wide range of human disease, the low efficiency of transfer and limited expression of the transferred gene have so far largely prevented any direct beneficial effect from being obtained. However, gene marker studies in which the transferred genes are used simply to track the individual components of the infused HSC have already shown their utility. Genetic marking may be used to identify cells capable of causing relapse after autologous bone marrow transplantation and to distinguish cells in the graft capable of preventing malignant disease. Marking may also be used to analyze the consequences of ex vivo or in vivo manipulations of the HSC which are intended to accelerate engraftment or augment gene transfer efficiencies. Information obtained from these studies should therefore not only improve the outcome of HSC based therapies, but also aid in the introduction of successful gene therapy protocols.
Bone Marrow Transplantation↗
[The chromosomal localization of the major genes for the quantitative traits (QTL) of wheat by using D chromosome gene markers].
The possibility of biochemical and morphological marker genes application for QTL and determination of their association with definite D chromosomes was shown on F2 populations of bread wheat from crossing of hexaploids AABBDD with different D subgenomes and the same genome AB part. Algorithm for calculation of the theoretical means for evaluation of differences according t-criterion was proposed and examined. The results of biometrical genetic analysis of the quantitative traits obtained by joint scaling Cavalli test using 6-10 different generations were used for calculation of theoretical means.
Chromosome Mapping↗
PACAP and NGF regulate common and distinct traits of the sympathoadrenal lineage: effects on electrical properties, gene markers and transcription factors in differentiating PC12 cells.
To determine the possible role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the development of the sympathoadrenal cell lineage, we have examined the effects of this neurotrophic peptide, in comparison to nerve growth factor (NGF), on the morphology, electrophysiological properties, expression of neuronal and neuroendocrine marker genes, and activity of transcription factors during differentiation of sympathoadrenal-derived cells, using the rat pheochromocytoma PC12 cell model. Both PACAP and NGF elicited rapid neurite outgrowth, which was accompanied by induction of cell excitability and the development of both sodium and calcium currents. Concurrently, PACAP and NGF increased the expression of a marker of synaptic vesicles. By contrast, PACAP, but not NGF, regulated the expression of different constituents of neuroendocrine large dense core vesicles in PC12 cells. Furthermore, PACAP and NGF differentially regulated the expression of mammalian achaete-scute homologue and paired homeobox 2b genes, transcription factors instrumental for sympathoadrenal development. To compare downstream effectors activated by PACAP and NGF, we studied the effects of these factors on the binding activity of consensus 12-O-tetradecanoylphorbol-13-acetate- and cAMP-responsive elements to nuclear extracts of differentiating PC12 cells. We found that both PACAP and NGF markedly increase the binding activity of these cis-regulatory sequences and that PACAP preferentially recruits activator protein-1-like transcription factors to these elements. Taken together, these results show that PACAP and NGF exert common as well as different effects on neuronal and neuroendocrine traits in differentiating PC12 cells, strongly suggesting that these two trophic factors could play complementary roles in the development of the sympathoadrenal cell lineage.
Adrenal Glands↗
Comparison of likelihood approaches for combined segregation and linkage analysis of a complex disease and a candidate gene marker under different ascertainment schemes.
We compared two joint likelihood approaches, with complete (L1) or without (L2) linkage disequilibrium, under different ascertainment schemes, for the genetic analysis of the disease trait and marker gene 1 in replicate 42. Joint likelihoods were computed without a correction for the selection scheme. For the different sampling schemes we have explored, our results suggest that L1 is a more powerful approach than L2 to detect major gene and covariate effects as well as to identify accurately gene x covariate interaction effects in a common and complex disease such as the Genetic Analysis Workshop 12 MG6 simulated trait.
Adult↗
A collation of marker gene and dermatoglyphic diversity at various levels of population differentiation.
The use of dermatoglyphic traits to describe interpopulational diversity among human populations at various levels of differentiation is compared with similar analysis of gene frequency data by means of nonparametric methods employing distance matrices and dendrograms, and by a partition of total variability into its between and within population components. Congruence of dermatoglyphics and gene markers appears to vary with level of population differentiation -- the association remains insignificant until racial level of differentiation is considered. Different pitfalls of the data used are mentioned. The interpretation of these findings is discussed by comparison with other non-human studies.
Biological Evolution↗
[Study of biochemical gene markers in the Mongolian gerbil (Meriones unguiculatus)].
The present study was conducted to analyze biochemical marker genes and to clarify genetic variation in 4 Mongolian gerbil (Meriones unguiculatus) strains (MGS/Sea, MON/Jms Gbs, Kwl: Mongolian Gerbil and Hos: Mongolian gerbil) maintained in Japan. Cellulose acetate, starch gel or agar gel electrophoresis was used. Of the 23 kinds of proteins detected, variation was found only in liver acid phosphatase (Acp2); no variation in other proteins was found within or among strains. The results suggest that these 4 Mongolian gerbil strains are genetically similar. A strain difference was found in the Acp2 locus of liver acid phosphatase. The Kwl: Mongolian Gerbil strain had a band of Acp2 locus, whereas MGS/Sea, MON/Jms and Hos: Mongolian gerbil strains did not.
Acid Phosphatase↗
Co-transformation using a negative selectable marker gene for the production of selectable marker gene-free transgenic plants.
A negative selectable marker gene, codA, was successfully co-transformed with a GUS reporter gene to develop selectable marker gene-free transgenic plants. The pNC binary vector contained a T-DNA harboring the codA gene next to the nptII gene, while a second binary vector, pHG, contained a GUS reporter gene. Tobacco plants ( Nicotiana tabacum cv. Samsun NN) were co-transformed via the mixture method with Agrobacterium tumefaciens LBA4404 strains harboring pNC and pHG, respectively. Seeds harvested from the co-transformants were sown on germination media containing 5-fluorocytosine (5-FC). Analysis of the progeny by GUS staining and PCR amplification revealed that all of the 5-FC-resistant R(1) plants were codA free, and that the codA gene segregated independently of the GUS gene. Because codA-free seedlings developed normally on 5-FC-containing medium, we suggest that co-transformation with negatively selectable markers is a viable method for the production of easily distinguished, selectable marker gene-free transgenic plants.
Agrobacterium tumefaciens↗
Linkage between bronchial responsiveness to methacholine and gene markers of IL-4 cytokine gene cluster and T-cell receptor alpha/delta gene complex in Korean nuclear families.
BACKGROUND: Several candidate genes have been reported to be linked to intermediate phenotypes of asthma in Caucasian populations. OBJECTIVE: To evaluate linkage between phenotypes of asthma and gene markers of high affinity IgE receptor-beta gene (D11S97), IL-4 cytokine gene cluster (IL-4R1), and T-cell receptor alpha/delta gene complex (D14S50) in Korean nuclear families. METHODS: Nuclear families (127 probands and their 130 siblings) for the linkage analysis were ascertained through asthmatic children. Linkages between total serum IgE response, skin responses to common aeroallergens, and bronchial responsiveness to methacholine were performed using a sib-pair approach. RESULTS: The square difference of the slope of the dose-response curve (DRS) between sib-pairs with two IL-4R1 identical alleles was smaller than with one or with neither IL-4R1 identical allele (P = 0.004). As for D14S50, the differences of DRS between sib-pairs with two identical alleles and with one identical allele were smaller than with neither identical alleles (P = 0.01). As for D11S97, no significant differences were observed among the groups with identical alleles of two, one or zero. With regard to total serum IgE levels, no significant linkage was found between this phenotype and the above three gene markers. As for skin responses to common aeroallergens, significant evidence was obtained to establish a linkage between this phenotype and the marker IL-4R1 (P = 0.01). However, no significant linkage was found between this phenotype and the markers D11S97 and D14S50. CONCLUSION: The expression of bronchial responsiveness to methacholine may be influenced by genetic factors in the IL-4 cytokine gene cluster and/or T-cell receptor alpha/delta gene complex, but the genetic influence of the FcepsilonRI-beta gene may be minimal in the expression of bronchial responsiveness in Korean nuclear families.
Adolescent↗
[Regulation of tumor marker gene expression].
Tumor marker is a group of proteins that specifically expressed in association with carcinogenic processes. Thus, studies of regulation mechanisms of the tumor marker genes are important for understanding the possible alteration of gene expression during neoplastic transformation. In this article, we described the molecular mechanisms of the regulation of two major tumor marker genes, i.e. human alpha-fetoprotein (AFP) gene and rat glutathione transferase P(GST-P) gene. Positive and negative mechanisms of each gene regulations are discussed.
Animals↗
Bias of the estimated recombination fraction and lod score due to an association between a disease gene and a marker gene.
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Alleles↗
The maize Knotted1 gene is an effective positive selectable marker gene for Agrobacterium-mediated tobacco transformation.
We have assessed the use of a homeobox gene knotted1 (kn1) from maize as a selectable marker gene for plant transformation. The kn1 gene under the control of cauliflower mosaic virus 35S promoter (35S::kn1) was introduced into Nicotiana tabacum cv. Xanthi via Agrobacterium-mediated transformation. Under nonselective conditions (without antibiotic selection) on a hormone-free medium (MS), a large number of transgenic calli and shoots were obtained from explants that were infected with Agrobacterium tumefaciens LBA4404 harboring the 35S::kn1 gene. On the other hand, no calli or shoots were produced from explants that were infected with an Agrobacterium strain harboring pBI121 (nptII selection) or from uninfected controls cultured under identical conditions. Relative to kanamycin selection conferred by nptII, the use of kn1 resulted in a 3-fold increase in transformation efficiency. The transgenic status of shoots obtained was confirmed by both histochemical detection of GUS activity and molecular analysis. The results presented here suggest that kn1 gene could be used as an effective alternative selection marker with a potential to enhance plant transformation efficiency in many plant species. With kn1 gene as a selection marker gene, no antibiotic-resistance or herbicide-resistance genes are needed so that potential risks associated with the use of these traditional selection marker genes can be eliminated.
Caulimovirus↗
Joint analysis of two microarray gene-expression data sets to select lung adenocarcinoma marker genes.
BACKGROUND: Due to the high cost and low reproducibility of many microarray experiments, it is not surprising to find a limited number of patient samples in each study, and very few common identified marker genes among different studies involving patients with the same disease. Therefore, it is of great interest and challenge to merge data sets from multiple studies to increase the sample size, which may in turn increase the power of statistical inferences. In this study, we combined two lung cancer studies using microarray GeneChip, employed two gene shaving methods and a two-step survival test to identify genes with expression patterns that can distinguish diseased from normal samples, and to indicate patient survival, respectively. RESULTS: In addition to common data transformation and normalization procedures, we applied a distribution transformation method to integrate the two data sets. Gene shaving (GS) methods based on Random Forests (RF) and Fisher's Linear Discrimination (FLD) were then applied separately to the joint data set for cancer gene selection. The two methods discovered 13 and 10 marker genes (5 in common), respectively, with expression patterns differentiating diseased from normal samples. Among these marker genes, 8 and 7 were found to be cancer-related in other published reports. Furthermore, based on these marker genes, the classifiers we built from one data set predicted the other data set with more than 98% accuracy. Using the univariate Cox proportional hazard regression model, the expression patterns of 36 genes were found to be significantly correlated with patient survival (p < 0.05). Twenty-six of these 36 genes were reported as survival-related genes from the literature, including 7 known tumor-suppressor genes and 9 oncogenes. Additional principal component regression analysis further reduced the gene list from 36 to 16. CONCLUSION: This study provided a valuable method of integrating microarray data sets with different origins, and new methods of selecting a minimum number of marker genes to aid in cancer diagnosis. After careful data integration, the classification method developed from one data set can be applied to the other with high prediction accuracy.
Adenocarcinoma↗
Selectable plasmid vectors with alternative and ultrasensitive histochemical marker genes.
Three different histochemical marker genes--E. coli beta-galactosidase gene (lacZ), Drosophila alcohol dehydrogenase gene (ADH) and human placenta alkaline phosphatase gene (ALP)--were cloned into a eukaryotic expression vector also containing the neomycin resistance gene. After calcium phosphate transfection and G418 sulfate selection of recipient BALB/c 3T3 cells, stable transfectants were pooled for histochemical staining. The lacZ-bearing cells produce aqua blue staining for beta-galactosidase; ADH-bearing cells, blue-black staining for alcohol dehydrogenase; and ALP-bearing cells, red staining for alkaline phosphatase. Cells carrying different marker genes can be easily differentiated by double-staining protocols. In addition, various photographic films can be used to enhance the colors of specific histochemically tagged cell classes. These plasmid vectors, providing selectability with the neomycin resistance gene and ultrasensitivity of alternative histochemical marker genes, will be very effective in virtually any biological system requiring analyses of multiple cell clones or classes in culture model systems or in situ.
3T3 Cells↗
Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis.
AIM: To determine the gene expression profile data for the whole liver during development of dimethylni-trosamine (DMN)-induced hepatic fibrosis. METHODS: Marker genes were identified for different types of hepatic cells, including hepatic stellate cells (HSCs), Kupffer cells (including other inflammatory cells), and hepatocytes, using independent temporal DNA microarray data obtained from isolated hepatic cells. RESULTS: The cell-type analysis of gene expression gave several key results and led to formation of three hypotheses: (1) changes in the expression of HSC-specific marker genes during fibrosis were similar to gene expression data in in vitro cultured HSCs, suggesting a major role of the self-activating characteristics of HSCs in formation of fibrosis; (2) expression of mast cell-specific marker genes reached a peak during liver fibrosis, suggesting a possible role of mast cells in formation of fibrosis; and (3) abnormal expression of hepatocyte-specific marker genes was found across several metabolic pathways during fibrosis, including sulfur-containing amino acid metabolism, fatty acid metabolism, and drug metabolism, suggesting a mechanistic relationship between these abnormalities and symptoms of liver fibrosis. CONCLUSION: Analysis of marker genes for specific hepatic cell types can identify the key aspects of fibrogenesis. Sequential activation of inflammatory cells and the self-supporting properties of HSCs play an important role in development of fibrosis.
Alanine Transaminase↗