bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression-based Genetic/Physical Maps of Single-Nucleotide Polymorphisms Identified by the Cancer Genome Anatomy Project
Authors: Clifford Robert , Edmonson Michael , Hu Ying , Nguyen Cu , Scherpbier Titia , Buetow Kenneth H. 
Published: July 2002

SNPs (Single-Nucleotide Polymorphisms), the most common DNA variant in humans, represent a valuable resource for the genetic analysis of cancer and other illnesses. These markers may be used in a variety of ways to investigate the genetic underpinnings of disease. In gene-based studies, the correlations between allelic variants of genes of interest and particular disease states are assessed. An extensive collection of SNP markers may enable entire molecular pathways regulating cell metabolism, growth, or differentiation to be analyzed by this approach. In addition, high-resolution genetic maps based on SNPs will greatly facilitate linkage analysis and positional cloning. The National Cancer Institute's CGAP-GAI (Cancer Genome Anatomy Project Genetic Annotation Initiative) group has identified 10,243 SNPs by examining publicly available EST (Expressed Sequence Tag) chromatograms. More than 6800 of these polymorphisms have been placed on expression-based integrated genetic/physical maps. In addition to a set of comprehensive SNP maps, we have produced maps containing single nucleotide polymorphisms in genes expressed in breast, colon, kidney, liver, lung, or prostate tissue. The integrated maps, a SNP search engine, and a Java-based tool for viewing candidate SNPs in the context of EST assemblies can be accessed via the CGAP-GAI web site (http://cgap.nci.nih.gov/GAI/). Our SNP detection tools are available to the public for noncommercial use.[The sequence data described in this paper have been submitted to the db SNP data library under accession nos. SS8196–SS18418.]
Additional Complexity on Human Chromosome 15q: Identification of a Set of Newly Recognized Duplicons (LCR15) on 15q11–q13, 15q24, and 15q26
Authors: Pujana Miguel Angel , Nadal Marga , Gratacòs Mònica , Peral Belén , Csiszar Katalin , González-Sarmiento Rogelio , Sumoy Lauro , Estivill Xavier 
Published: July 2002

Several cytogenetic alterations affect the distal part of the long arm of human chromosome 15, including recurrent rearrangements between 12p13 and 15q25, which cause congenital fibrosarcoma (CFS). We present here the construction of a BAC/PAC contig map that spans 2 Mb from the neurotrophin-3 receptor (NTRK3) gene region on 15q25.3 to the proximal end of the Bloom's syndrome region on 15q26.1, and the identification of a set of new chromosome 15 duplicons. The contig reveals the existence of several regions of sequence similarity with other chromosomes (6q, 7p, and 12p) and with other 15q cytogenetic bands (15q11–q13 and 15q24). One region of similarity maps on 15q11–q13, close to the Prader-Willi/Angelman syndromes (PWS/AS) imprinting center. The 12p similar sequence maps on 12p13, at a distance to the ets variant 6 (ETV6) gene that is equivalent on 15q26.1 to the distance to the NTRK3 gene. These two genes are the targets of the CFS recurrent translocations, suggesting that misalignments between these two chromosomes regions could facilitate recombination. The most striking similarity identified is based on a low copy repeat sequence, mainly present on human chromosome 15 (LCR15), which could be considered a newly recognized duplicon. At least 10 copies of this duplicon are present on chromosome 15, mainly on 15q24 and 15q26. One copy is located close to a HERC2sequence on the distal end of the PWS/AS region, three around the lysyl oxidase-like (LOXL1) gene on 15q24, and three on 15q26, one of which close to the IQ motif containing GTPase-activating protein 1 (IQGAP1) gene on 15q26.1. These LCR15 span between 13 and 22 kb and contain high identities with the golgin-like protein (GLP) and the SH3 domain-containing protein (SH3P18) gene sequences and have the characteristics of duplicons. Because duplicons flank chromosome regions that are rearranged in human genomic disorders, the LCR15 described here could represent new elements of rearrangements affecting different regions of human chromosome 15q.[The sequence data described in this paper have been submitted to EMBL GenBank with the accession nos.AJ272070, AJ276448, AJ276449, AJ286892-AJ286929, AJ400620, AJ400621,AJ400817-AJ400820, AJ277869AJ277874.]
A Bacterial Artificial Chromosome Library for Sequencing the Complete Human Genome
Authors: Osoegawa Kazutoyo , Mammoser Aaron G. , Wu Chenyan , Frengen Eirik , Zeng Changjiang , Catanese Joseph J. , de Jong Pieter J. 
Published: July 2002

A 30-fold redundant human bacterial artificial chromosome (BAC) library with a large average insert size (178 kb) has been constructed to provide the intermediate substrate for the international genome sequencing effort. The DNA was obtained from a single anonymous volunteer, whose identity was protected through a double-blind donor selection protocol. DNA fragments were generated by partial digestion with EcoRI (library segments 1–4: 24-fold) and MboI (segment 5: sixfold) and cloned into the pBACe3.6 and pTARBAC1 vectors, respectively. The quality of the library was assessed by extensive analysis of 169 clones for rearrangements and artifacts. Eighteen BACs (11%) revealed minor insert rearrangements, and none was chimeric. This BAC library, designated as “RPCI-11,” has been used widely as the central resource for insert-end sequencing, clone fingerprinting, high-throughput sequence analysis and as a source of mapped clones for diagnostic and functional studies.The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AQ936150–AQ936491.]
A Predictive Model for Regulatory Sequences Directing Liver-Specific Transcription
Authors: Krivan William , Wasserman Wyeth W. 
Published: July 2002

The identification and interpretation of the regulatory signals within the human genome remain among the greatest goals and most difficult challenges in genome analysis. The ability to predict the temporal and spatial control of transcription is likely to require a combination of methods to address the contribution of sequence-specific signals, protein–protein interactions and chromatin structure. We present here a new procedure to identify clusters of transcription factor binding sites characteristic of sequence modules experimentally verified to direct transcription selectively to liver cells. This algorithm is sufficiently specific to identify known regulatory sequences in genes selectively expressed in liver, promising acceleration of experimental promoter analysis. In combination with phylogenetic footprinting, this improvement in the specificity of predictions is sufficient to motivate a scan of the human genome. Potential regulatory modules were identified in orthologous human and rodent genomic sequences containing both known and uncharacterized genes.[Supplementary data and the submission of sequences for analysis are available athttp://www.cgb.ki.se/krivan/liver/liver.html.]
Computation-Based Discovery of Related Transcriptional Regulatory Modules and Motifs Using an Experimentally Validated Combinatorial Model
Authors: Halfon Marc S. , Grad Yonatan , Church George M. , Michelson Alan M. 
Published: July 2002

Gene expression is regulated by transcription factors that interact with cis-regulatory elements. Predicting these elements from sequence data has proven difficult. We describe here a successful computational search for elements that direct expression in a particular temporal-spatial pattern in the Drosophila embryo, based on a single well characterized enhancer model. The fly genome was searched to identify sequence elements containing the same combination of transcription factors as those found in the model. Experimental evaluation of the search results demonstrates that our method can correctly predict regulatory elements and highlights the importance of functional testing as a means of identifying false-positive results. We also show that the search results enable the identification of additional relevant sequence motifs whose functions can be empirically validated. This approach, combined with gene expression and phylogenetic sequence data, allows for genome-wide identification of related regulatory elements, an important step toward understanding the genetic regulatory networks involved in development.[Sequence data reported in this paper have been deposited in GenBank with accession nos. AF513981 (EveMHE) and AF513982 (Hbr DME). Supplementary material is available online at http://www.genome.org. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: R. Blackman]
Transcriptional Regulation of the Stem Cell Leukemia Gene (SCL) — Comparative Analysis of Five Vertebrate SCL Loci
Authors: Göttgens Berthold , Barton Linda M. , Chapman Michael A. , Sinclair Angus M. , Knudsen Bjarne , Grafham Darren , Gilbert James G.R. , Rogers Jane , Bentley David R. , Green Anthony R. 
Published: July 2002

The stem cell leukemia (SCL) gene encodes a bHLH transcription factor with a pivotal role in hematopoiesis and vasculogenesis and a pattern of expression that is highly conserved between mammals and zebrafish. Here we report the isolation and characterization of the zebrafish SCL locus together with the identification of three neighboring genes, IER5,MAP17, and MUPP1. This region spans 68 kb and comprises the longest zebrafish genomic sequence currently available for comparison with mammalian, chicken, and pufferfish sequences. Our data show conserved synteny between zebrafish and mammalian SCL and MAP17 loci, thus suggesting the likely genomic domain necessary for the conserved pattern ofSCL expression. Long-range comparative sequence analysis/phylogenetic footprinting was used to identify noncoding conserved sequences representing candidate transcriptional regulatory elements. The SCL promoter/enhancer, exon 1, and the poly(A) region were highly conserved, but no homology to other known mouseSCL enhancers was detected in the zebrafish sequence. A combined homology/structure analysis of the poly(A) region predicted consistent structural features, suggesting a conserved functional role in mRNA regulation. Analysis of the SCL promoter/enhancer revealed five motifs, which were conserved from zebrafish to mammals, and each of which is essential for the appropriate pattern or level ofSCL transcription.[The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: N. Tanese.]
Caenorhabditis elegans Has Scores of hedgehogRelated Genes: Sequence and Expression Analysis
Authors: Aspöck Gudrun , Kagoshima Hiroshi , Niklaus Gisela , Bürglin Thomas R. 
Published: July 2002

Previously, we have described novel families of genes, warthog(wrt) and groundhog (grd), inCaenorhabditis elegans. They are related to Hedgehog (Hh) through the carboxy-terminal autoprocessing domain (called Hog or Hint). A comprehensive survey revealed 10 genes with Hog/Hint modules in C. elegans. Five of these are associated with a Wart domain in wrt genes, and three with multiple copies of the Ground domain in grd genes. Both the Wart domain and the Ground domain occur also in genes encoding no Hog domain. Further, we define a new group of genes related to the grd genes, calledground-like (grl). Overall, C. elegans has more than 50 genes belonging to these gene families. Phylogenetic and sequence analysis shows that the wrt, grd, and grlgenes are derived from each other. Further examination reveals a sequence motif with similarity to the core of the amino-terminal-signaling domain of Hh proteins. Our data suggest that the wrt, grd, grl, and hh genes are derived from a single ancestral gene. wrt, grd, and grl genes are also present in other nematodes, but so far not in any other phyla. Conversely, hh is not found presently in C. elegansnor other nematodes. Thus, the nematode genes could be the homologs of Hh molecules in other phyla. The membrane molecule Patched has been shown previously to be a receptor of Hh. Many Patched-related proteins are present in C. elegans, which may be targets of thehh-related genes. No Hedgehog-interacting protein (Hip) was found. We analyzed the expression patterns of eight wrt and eight grd genes. The results show that some closely related genes are expressed in the same tissues, but, overall, the expression patterns are diverse, comprising hypodermis, seam cells, the excretory cell, sheath and socket cells, and different types of neurons.[Hog domain-containing genes are available as an online supplement table at www.genome.org. The sequence data described in this paper have been submitted to the GenBank data library under accession nos.AF139522, AF139520, AF139521]
The Genexpress IMAGE Knowledge Base of the Human Muscle Transcriptome: A Resource of Structural, Functional, and Positional Candidate Genes for Muscle Physiology and Pathologies
Authors: Piétu Geneviève , Eveno Eric , Soury-Segurens Béatrice , Fayein Nicole-Adeline , Mariage-Samson Régine , Matingou Christiane , Leroy Elisabeth , Dechesne Claude , Krieger Sabine , Ansorge Wilhelm , Reguigne-Arnould Isabelle , Cox David , Dehejia Anindya , Polymeropoulos Mihael H. , Devignes Marie-Dominique , Auffray Charles 
Published: July 2002

Sequence, gene mapping, and expression data corresponding to 910 genes transcribed in human skeletal muscle have been integrated to form the muscle module of the Genexpress IMAGE Knowledge Base. Based on cDNA array hybridization, a set of 14 transcripts preferentially or specifically expressed in muscle have been selected and characterized in more detail: Their pattern of expression was confirmed by Northern blot analysis; their structure was further characterized by full-insert cDNA sequencing and cDNA extension; the map location of the corresponding genes was refined by radiation hybrid mapping. Five of the 14 selected genes appear as interesting positional and functional candidate genes to study in relation with muscle physiology and/or specific orphan muscular pathologies. One example is discussed in more detail. The expression profiling data and the associated Genexpress Index2 entries for the 910 genes and the detailed characterization of the 14 selected transcripts are available from a dedicated Web server athttp://idefix.upr420.vjf.cnrs.fr/IMAGE/Page_unique/welcome_muscles.html. The database has been organized to provide the users with a working space where they can find curated, annotated, integrated data for their genes of interest. Different navigation routes to exploit the resource are discussed.[Tables A and B are available as supplementary information at www.genome.org and also athttp://idefix.upr420.vjf.cnrs.fr/IMAGE/Page_unique/welcome_muscles.html.]
The Cyanobacterial Thioredoxin Gene Is Required for Both Photoautotrophic and Heterotrophic Growth
Authors: Navarro F. , Florencio F. J. 
Published: July 2002

Abstract
The gene encoding thioredoxin in the facultative heterotrophic cyanobacterium Synechocystis sp. PCC 6803 (trxA) has been cloned by heterologous hybridization using the corresponding gene trxM from the cyanobacterium Anacystis nidulans as a probe. The deduced amino acid sequence of trxA predicts a protein of relative molecular weight of 11,750 and has strong identity with its cyanobacterial counterparts and other m-type thioredoxins of photosynthetic eukaryotes. The trxA gene has been expressed in Escherichia coli as a functional protein of 12 kD and has been shown by western blot analysis to be the same size as in Synechocystis. The trxA gene is transcribed in Synechocystis as a single transcript of 450 nucleotides and accumulates to the same level under photo synthetic and heterotrophic growth conditions. The trxA gene was inactivated with a kanamycin-resistant cassette, and total segregation of the disrupted trxA gene was obtained only when the trxM gene from A. nidulans (E.D.G. Muller, B.B. Buchanan [1989] J Biol Chem 264: 4008–4014) was simultaneously expressed in Synechocystis. Our results suggest an essential role of thioredoxin not only when cells grow photosynthetically but also under heterotrphic conditions.
Composition of Photosystem II Antenna in Light-Harvesting Complex II Antisense Tobacco Plants at Varying Irradiances
Authors: Flachmann R. 
Published: July 2002

Abstract
Plants with genes coding for chlorophyll a/b-binding proteins of light-harvesting complex II (LHCII) in antisense orientation (Lhcb) that are characterized by severely reduced Lhcb transcript levels (below 10% of wild type) do not show a bleached phenotype due to a specific loss of the polypeptide. To produce such a phenotype, a conceptually different antisense approach was tested with a dual-functional transcript encoding the gene for hygromycin phosphotransferase and the transit sequence of Lhcb1–2 in the antisense orientation. Using increasing concentrations of hygromycin, transformants with Lhcb steady-state levels as low as 9% of wild type were regenerated and grown in a growth chamber. Together with Lhcb antisense plants obtained in an earlier study, these antisense plants were analyzed biochemically for their photosystem II (PSII) antenna composition under varying light conditions. All antisense plants showed a characteristic low-irradiance-induced increase of their PSII antenna size as determined by higher chlorophyll concentrations, an increased content of LHCII, and a constant chlorophyll b-to-lutein ratio in comparison with control plants. One to 5% of the total Lhcb transcript amount was sufficient to allow unrestricted formation of the PSII antenna at low irradiance, suggesting that LHCII biogenesis is not controlled primarily by transcription.
Negative Regulation in the Expression of a Sugar-Inducible Gene in Arabidopsis thaliana (A Recessive Mutation Causing Enhanced Expression of a Gene for β-Amylase)
Authors: Mita S. , Hirano H. , Nakamura K. 
Published: July 2002

Abstract
Expression of a β-amylase gene of Arabidopsis thaliana (ATβ-Amy)is regulated by sugars. We identified a mutant, hba1, in which the level of expression of ATβ-Amy in leaves of plants that had been grown in a medium with 2% sucrose was significantly higher than that in wild-type plants. Higher than wild-type levels of β-amylase in hba1 plants depended on the presence of 1 to 2% sucrose or 1% glucose in the medium, whereas leaves of mutant plants grown with higher levels of sugars had β-amylase activities similar to those in leaves of wild-type plants. The hba1 phenotype was recessive and did not affect levels of sugars and starch in leaves. It is proposed that expression of ATβ-Amy is regulated by a combination of both positive and negative factors, dependent on the level of sugars, and that HBA1 might function to maintain low-level expression of ATβ-Amy until the level of sugars reaches some high level. Results of crosses of hba1 plants with transgenic plants that harbored an ATβ-Amy:GUS transgene with 1587 bp of the 5[prime]-upstream region suggested that HBA1 affects expression of ATβ-Amy in trans. The hba1 plants also had growth defects and elevated levels of anthocyanin in their petioles. However, sugar-regulated changes in levels of several mRNAs other than β-amylase mRNA were unaffected in hba1 plants, suggesting that only a subset of sugar-regulated genes is under the control of HBA1.
The Distal Part of the Transition Zone Is the Most Aluminum-Sensitive Apical Root Zone of Maize1
Authors: Sivaguru Mayandi , Horst Walter J. 
Published: July 2002

Abstract
For a better understanding of Al inhibition of root elongation, knowledge of the morphological and functional organization of the root apex is a prerequisite. We developed a polyvinyl chloride-block technique to supply Al (90 μm monomeric Al) in a medium containing agarose to individual 1-mm root zones of intact seedlings of maize (Zea mays L. cv Lixis). Root elongation was measured during a period of 5 h. After Al treatment, callose (5 h) and Al (1 h) contents of individual 1-mm apical root segments were determined. For comparison, callose and Al levels were also measured in root segments after uniform Al supply in agarose blocks to the 10-mm root apex. Only applying Al to the three apical 1-mm root zones inhibited root elongation after 1 h. The order of sensitivity was 1 to 2 &gt; 0 to 1 &gt; 2 to 3 mm. In the 1- to 2-mm root zone high levels of Al-induced callose formation and accumulation of Al was found, independently of whether Al was applied to individual apical root zones or uniformly to the whole-root apex. We conclude from these results that the distal part of the transition zone of the root apex, where the cells are undergoing a preparatory phase for rapid elongation (F. Baluška, D. Volkmann, P.W. Barlow [1996] Plant Physiol 112: 3–4), is the primary target of Al in this Al-sensitive maize cultivar.
Fast Induction of High-Affinity HCO3− Transport in Cyanobacteria1
Authors: Sültemeyer Dieter , Klughammer Barbara , Badger Murray R. , Dean Price G. 
Published: July 2002

Abstract
The induction of a high-affinity state of the CO2-concentration mechanism was investigated in two cyanobacterial species, Synechococcus sp. strain PCC7002 and Synechococcus sp. strain PCC7942. Cells grown at high CO2 concentrations were resuspended in low-CO2 buffer and illuminated in the presence of carbonic anhydrase for 4 to 10 min until the inorganic C compensation point was reached. Thereafter, more than 95% of a high-affinity CO2-concentration mechanism was induced in both species. Mass-spectrometric analysis of CO2 and HCO3− fluxes indicated that only the affinity of HCO3− transport increased during the fast-induction period, whereas maximum transport activities were not affected. The kinetic characteristics of CO2uptake remained unchanged. Fast induction of high-affinity HCO3− transport was not inhibited by chloramphenicol, cantharidin, or okadaic acid. In contrast, fast induction of high-affinity HCO3−transport did not occur in the presence of K252a, staurosporine, or genistein, which are known inhibitors of protein kinases. These results show that induction of high-affinity HCO3− transport can occur within minutes of exposure to low-inorganic-C conditions and that fast induction may involve posttranslational phosphorylation of existing proteins rather than de novo synthesis of new protein components.
Relationship between CO2 Assimilation, Photosynthetic Electron Transport, and Active O2 Metabolism in Leaves of Maize in the Field during Periods of Low Temperature1
Authors: Fryer Michael J. , Andrews James R. , Oxborough Kevin , Blowers David A. , Baker Neil R. 
Published: July 2002

AbstractMeasurements of the quantum efficiencies of photosynthetic electron transport through photosystem II (φPSII) and CO2 assimilation (φCO2) were made simultaneously on leaves of maize (Zea mays) crops in the United Kingdom during the early growing season, when chilling conditions were experienced. The activities of a range of enzymes involved with scavenging active O2 species and the levels of key antioxidants were also measured. When leaves were exposed to low temperatures during development, the ratio of φPSII/φCO2 was elevated, indicating the operation of an alternative sink to CO2 for photosynthetic reducing equivalents. The activities of ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, glutathione reductase, and superoxide dismutase and the levels of ascorbate and α-tocopherol were also elevated during chilling periods. This supports the hypothesis that the relative flux of photosynthetic reducing equivalents to O2 via the Mehler reaction is higher when leaves develop under chilling conditions. Lipoxygenase activity and lipid peroxidation were also increased during low temperatures, suggesting that lipoxygenase-mediated peroxidation of membrane lipids contributes to the oxidative damage occurring in chill-stressed leaves.