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Project The fission yeast Schizosaccharomyces pombe is a unicellular ascomycete. It has a simple eukaryotic genome of approximately equivalent size to that of budding yeast, Saccharomyces cerevisiae, at around 14 Mb. Unlike S. cerevisiae, the S. pombe genome is spread between only three chromosomes. The S. pombe sequencing project was initiated at the Sanger Centre as a pilot project in 1995. Further funding was secured from the European Commission in 1996 to allow a consortium of European Sequencing Laboratories to continue the project.
- A 3-D Digital Anatomical Atlas and Database of Gene
Genetic information is expressed in complex and ever-changing patterns throughout the development of the mammalian embryo. A description of these patterns and how they relate to the emerging tissue structure of the embryo is crucial for our understanding of the network of genetic interactions that underlie the processes of normal development, disease and evolution. Studies of gene expression are rapidly producing a very large amount of information relating to these complex patterns. This creates serious difficulties in publishing, scanning and accessing the information. It also creates difficulties in making comparisons between the expression of different genes in order to assess the possibility of complex networks of genetic interaction. These problems cannot be addressed by conventional means of publication, but will require the development of a widely accessible, electronic database. Moreover, text descriptions of gene expression are often of limited value partly as a consequence of the spatial complexity of the patterns and partly because domains of gene expression do not necessarily correspond to named anatomical structures.
- A Consolidated Linkage Map for the Zebrafish
This linkage map shows the positions of 652 markers genotyped in one or both of two haploid mapping panels. Centromere locations determined by half-tetrad analysis are shown as black rectangles (95% confidence interval). RAPD marker names indicate the primer name assigned by Operon Technologies, Inc., followed by the approximate size in base pairs of the amplified marker. Letters in parentheses indicate the parental origin of markers (A, AB; C, C32; D, DAR; S, SJD). Parentheses containing two letters separated by a slash (C/S) indicate a codominant marker. See the Materials and Methods section of the source article for further discussion of nomenclature. Markers enclosed in angle brackets (<>) have some uncertainty of local marker order due to integration of maps from the two mapping panels. RAPD markers converted to STSs are indicated by their RAPD name followed by a * (star, Sequence Tagged RAPD). Cross bars are shown every 2cM.
- A high throughput screen to identify novel secreted and transmembrane proteins i
Secreted and transmembrane proteins play an essential role in intercellular communication during the development of multicellular organisms. As only a small number of these genes have been characterized, we developed a screen for genes encoding extracellular proteins that are differentially expressed during Drosophila embryogenesis. Our approach utilizes a new method for screening large numbers of cDNAs by whole embryo in situ hybridization. The cDNA library for the screen was prepared from rough endoplasmic reticulum-bound mRNA, and is therefore enriched in clones encoding membrane and secreted proteins. To increase the prevalence of rare cDNAs in the library, the library was normalized using a novel method based on cDNA hybridization to genomic DNA-coated beads. In total, 2518 individual cDNAs from the normalized library were screened by in situ hybridization, and 917 of these cDNAs represent genes differentially expressed during embryonic development. Sequence analysis of 1001 cDNAs indicated that 811 represent genes not previously described in Drosophila. Expression pattern photographs and partial DNA sequences have been assembled in a database publicly available at the Berkeley Drosophila Genome Project website (http://www.fruitfly.org). The identification of a large number of genes encoding proteins involved in cell-cell contact and signaling will advance our knowledge of the mechanisms by which multicellular organisms and their specialized organs develop.
- A P1-based physical map of the Drosophila euchromatic genome
A PCR-based Sequence tagged site (STS) content mapping strategy has been used to generate a physical map with 90% coverage of the 120 Mb euchromatic portion of the Drosophila genome. To facilitate map completion, the bulk of the STS markers was chosen in a nonrandom fashion. To ensure that all contigs were localized in relation to each other and the genome, these contig-building procedures were performed in conjunction with a large-scale in situ hybridization analysis of randomly selected clones from a Drosophila genomic library that had been generated in a P1 cloning vector. At this point, the map consists of 649 contigs with an STS localized on average every 50 kb. This is the first whole genome that has been mapped based on a library constructed with large inserts in a vector that is maintained in Escherichi coli as a single copy plasmid.
- abdominal-A
As recently as 1986, models of the bithorax complex of genes posited not three genes, (abdominal A, Abdominal B and Ultrabithorax) as is currently assumed, but seven or eight, each independently regulated and controlled by the repressor Polycomb. This earlier model of development suggested that the cuticular phenotype of each segment depended on an array of up to eight BX-C substances elaborated in each segment. Only with the cloning of the bithorax complex genes (Regulski, 1985) was the picture more accurately understood. It then became clear that only three genes, not eight, were responsible for all the phenotypes observed.
- Abdominal-B
Pair-rule and segment polarity genes are responsible for determining the uniformity of different segments, in contrast to homeodomain proteins that are responsible for establishing the diversity between segments. Abdominal-B acts in three germ cell layers to fulfill this latter function. Abdominal-B is the last in linkage order and the most posterior acting of the linked homeodomain proteins of the bithorax. Abdominal-B is unique among the homeotics in that it is transcribed in two forms; a regulatory (r) protein and a morphogenic (m) protein. Regulatory transcripts of Abdominal-B act as repressors, suppressing embryonic ventral epidermal structures in the 8th and 9th segments of the abdomen. Thus ABD-B r and m proteins are critically involved in establishing cell fate in the tail segments of the fly.
- Abl oncogene
The Philadelphia chromosomal translocation is responsible for the fusion of two genes, ABL and BCR. Recognized as a frequently occuring aberrant chromosome in acute lymphoblastic leukemia, it was understood more than a decade ago that the Philadelphia chromosome occurs as a result of a recombination between two genes: the cellular ABL gene on chromosome 9, and BCR (breakpoint cluster region) gene located on chromosome 22. The Drosophila Abelson (Abl) protein is a homolog of mammalian c-Abl the wild-type gene coding for the ABL sequence found in the BRC/ABL hybrid protein. The BCR/ABL oncogene product, derived from this specific chromosomal translocation is present in Philadelphia chromosome-postive acute lymphoblastic leukemia. Despite its homology to c-Abl, the wild type mammalian protein, Drosophila ABL protein shows distinct properties and functional differences from c-Abl that suggest the two proteins are not strictly comparable.
- About Mouse Genome Informatics (MGI)
The Mouse Genome Informatics (MGI) Web site provides integrated access to various sources for information on the genetics and biology of the laboratory mouse. The MGI resource comprises the Mouse Genome Database (MGD), the Gene Expression Database (GXD) and the Encyclopedia of the Mouse Genome (Encyclopedia).In addition .MGI provides access to related resources including the Mouse Tumor Biology database and the Rat Data resource.
- abrupt
- achaete
- amnesiac
- anachronism
- AMS Analytical micro Analytical micro-Systems: devices and chemicals for bioanalytics, material scien
Analytical micro-Systems (Regensburg, Germany) We offer devices and chemicals for bioanalytics, material science, biophysics: SPR spectrometer, impedance analyzer, functionalized alkylthiols; coating of gold electrodes by stable organic compounds for further immobilization of biomolecules
- Antennapedia
- anterior open
- APC-like
- apterous
- araucan and caupolican
- argos
- aristaless
- armadillo
- arrest
- Arrowhead
- ARS elements
- asense
- atonal
- bag of marbles
- bagpipe
- BarH1 and BarH2
- basket
- BDGP Publications and Laboratory Methods
BDGP Publications and Laboratory Methods
- Bearded
- Bicaudal D
- bicoid
- big brain
- Biodatabases Biodatabases
To-Oracle database migration, bio-database design and maintenance, data-mining
- Biologie Leistunskurs
Biologielexikon, Biologiereferate und Biologieabituraufgaben für Schüler
- Biologieprojekte
Bioakustik, Ethologie, Hirsche, Wildschweinee, Rotwild, Damwild, Genetik, Humangenetik, Kaspar hauser, Gentechnik, Anthropologie, Neandertaler, Rhein, Pfaffendorf, Baum, Bäume, Computereinsatz, Sonnenfinsternis, Flechten, Wachstum
- Biomedpage Biomedpage- Die wissenschaftliche Resourcensammlung für die Molekularbiologie un
Methodensammlungen, Kostenfreie Datenbankrecherche und eine umfangreiche Sammlung nützlicher Links zu den Bereichen Hefe Two-Hybrid Systeme, C. elegans Genetik, Molekularbiologie und Bioanalytik
- BIOTECH GmbH BioTechnologieZentrum Hennigsdorf
Technologie- und Gründerzentrum für humanmedizinische Biotechnologie mit diagnostischen und therapeutischen Schwerpunkten. Kooperation mit B.R.A.H.M.S Diagnostica GmbH. Start into market Services. Existenzgründung Biotechnologie Forschung B.R.A.H.M.S Vertrieb Diagnostik Investition Förderung
- blistered
- bnormal chemosensory jump 6
- brachyenteron
- brahma
- brainiac
- branchless
- breathless
- bride of sevenless
- broad
- bunched
- buttonhead
- buttonless
- cactus
- Candida albicans synonyms
- Candida Chromosomes
There are several chromosome numbering systems in the Candida albicans literature. The numbering system used to present our map information is described in the references below. It is based on the scheme adopted at the first ASM Conference on Candida which numbered the chromosomes 1 to 7 largest to smallest. The largest band in the electrophoretic karyotype was subsequently discovered to include two linkage groups. The additional linkage group is variable in size because of the presence of the tandemly arrayed genes for the ribosomal RNAs. We call this linkage group chromosome R.
- Candida Methods
- Candida molecular epidemiology
- Candida taxonomy
- Caulobacter crescentus overview
Caulobacter crescentus is one of the best understood examples of an organism that posesses true intrinsic asymmetry. Every cell division gives rise to two different cell types, a motile, flagellum-bearing swarmer cell and a sessile stalked cell. These two cell types differ not only in motility, but also in the complement of genes that they express and in their capacity to reinitiate chromosomal DNA replication. Asymmetry is generated in the predivisional cell through the differential targeting of flagellar and chemotaxis proteins, and through compartment-specific gene regulation.
- Chromosome 1
- Chromosome 2
- Chromosome 3
- Chromosome 4
- Chromosome 5
- Chromosome 6
- Chromosome 7
- Chromosome R
- Danish Centre for Human Genome Research
- Diving into the Gene Pool
- DNA Isolation Protocols for P1 Clones
This is a rapid alkaline lysis miniprep method for isolating DNA from large P1 clones, revised 12/10/97 by Barret Pfeiffer. It is a modification of a standard method that uses no organic extractions or columns. The method works very well for doing analytical restriction digests of P1 clones and can be scaled up if necessary. With slight alterations this procedure can also be used for routine analysis of M13 RF, plasmid, and cosmid DNAs.
- Effects of GGF/neuregulins on neuronal survival and neurite outgrowth
We have examined the expression of neuregulin and its putative receptors, erbB2/neu, erbB3 and erbB4/tyro2 during retinal development, and tested several potential functions of this class of molecules in dissociated rat retinal cell cultures. At least one form of neuregulin is expressed in the retina, from the earliest stages of retinal development examined; in addition, all three of the known receptors are expressed by retinal neurons in a developmentally regulated manner. When added to cultures of embryonic or neonatal rat retinal cells, neuregulin (rhGGF2) promotes survival and neurite extension from retinal neurons in a dose-dependent manner. These results indicate that in addition to their well described effects on glia, the neuregulins also have direct effects on central nervous system neurons.
- EST - Gene Links
598 previously identified Drosophila Melanogaster genes have been found among the EST libraries. This represents 44.7% of the sequenced Drosophila genes.
- Establishment of a Somatic Cell Hybrid Panel for the Horse
Recent developments in molecular biology have led to a rapid expansion in the construction of genetic maps for mammalian species. However, the construction of gene maps for domestic animal species has been slow to start. At present there are only 25 genes mapped to 6 linkage groups in the horse, which reflects that only a few laboratories are actively engaged in constructing a gene map for the horse. The development of a horse map will significantly contribute to the development of selection markers for performance and disease traits. Gene mapping will contribute to the indentification of loci responsible for genetic diseases or other traits of interest. The assignment of two or more markers to each chromosome will allow comparative mapping based on the more established mammalian gene maps, such as the human or mouse map.
- Establishment of the Dorsal nuclear localization gradient
The pattern along the dorsoventral axis of the Drosophila embryo is determined by a nuclear localization gradient of the transcription factor Dorsal. On the ventral side of the embryo Dorsal is present only within the nuclei. It is distributed, however, between the cytoplasm and the nuclei on lateral positions, and restricted to the cytoplasm on the dorsal side. Dorsal regulates the expression of its target genes, for example twist and zerknüllt, in dependence of its nuclear concentration, so that a stripe-like pattern of gene expression domains along the anterior-posterior axis emerges.
- European Drosophila Genome Project (EDGP)
The European Drosophila Genome Project has the objective of sequencing the X chromosome of Drosophila melanogaster. Divisions 1 to 3 (about 3-3.5 Mbases) will be sequenced by the end of the year 1999. Sequencing is based on the cosmid physical map, constructed by the European Drosophila Physical Mapping Project.
- Evolutionary Genetics of Insertion
Sequences
The proposed research in the Hartl laboratory has been to develop E coli and related species for use as experimental organisms in population genetics and evolution. Theoretical models for the distribution and abundance of transposable insertion sequences (IS) in natural isolate of E coli have been developed and tested against extensive data. The evolution of insertion sequences will be studied at the level of DNA sequences within and among host species. The level of variation among three families of IS elements in E coli isolates has already been determined.
- Fertilization and the block to polyspermy
Sperm-egg interactions result in a cascade of molecular responses that include exocytosis of the cortical granules. This secretory event functions in the permanent block to polyspermy that most eggs rely upon for fertilization, and in the formation of a protected environment for early embryonic development. We are examining the contents of the cortical granules to understand their function in the modification of the egg cell surface and extracellular matrix. Our functional characterization includes a molecular analysis of the protease and peroxidase activities, the structural proteins of the fertilization envelope, and the major protein of the extraembryonic matrix, hyalin.
- Fibroblast growth factors are necessary for neural retina but not pigmented
During eye development, optic vesicles evaginate laterally from the neural tube and develop into two bilayered eye cups that are composed of an outer pigment epithelium layer and an inner neural retina layer. Despite their similar embryonic origin, the pigment epithelium and neural retina differentiate into two very distinct tissues. Previous studies have demonstrated that the developmental potential of the pigmented epithelial cells is not completely restricted; until embryonic day 4.5 in chick embryos, the cells are able to switch their phenotype and differentiate into neural retina when treated with fibroblast growth factors (FGF) (Park, C. M., and Hollenberg, M. J. (1989). Dev. Biol. 134, 201-205; Pittack, C., Jones, M., and Reh, T. A. 1991). Development 113, 577-588; Guillemot, F. and Cepko, C. L. (1992). Development 114, 743-754). These studies motivated us to test whether FGF is necessary for neural retina differentiation during the initial stages of eye cup development. Optic vesicles from embryonic day 1.5 chick were cultured for 24 hours as explants in the presence of FGF or neutralizing antibodies to FGF2. The cultured optic vesicles formed eye cups that contained a lens vesicle, neural retina and pigmented epithelium, based on morphology and expression of neural and pigmented epithelium-specific antigens. Addition of FGF to the optic vesicles caused the presumptive pigmented epithelium to undergo neuronal differentiation and, as a consequence, a double retina was formed. By contrast, neutralizing antibodies to FGF2 blocked neural differentiation in the presumptive neural retina, without affecting pigmented epithelial cell differentiation. These data, along with evidence for expression of several FGF family members and their receptors in the developing eye, indicate that members of the FGF family may be required for establishing the distinction between the neural retina and pigmented epithelium in the optic vesicle
- Fin development
We are studying the development of the pectoral fins of the zebrafish, as they are considered to be homologous to the tetrapod forelimbs. We have carried out a detailed study of the development of the wildtype fins, and are now in the process of analysing mutants that show defects in fin development. Embryos mutant in babyface, sonic you, and dackel either show a reduced or an almost absent pair of pectoral fins. Analysis of double mutants has begun to provide insight into the interaction of particular genes, and experimental studies are under way to elucidate which structures of the fin can be considered homologous in function to their tetrapod counterparts (e.g., is the apical ectodermal fold in fish equivalent to the AER in tetrapodsNULL).
- Fishing for genes: Fugu expands (but its genome doesn't) genome doesn't
he major goal of the human genome project must be to identify, sequence, characterise and assign specific function to all the genes spread through our 3,000 Mbp of haploid DNA. Due to the uniformity and simplicity of the DNA code, it is not an easy task to identify genes even after the region in which they lie has been fully sequenced. The average length of a human coding sequence in the DNA databases is approximately 1.2 Kbp and sensible estimates of the total number of genes in the human genome lie between 50 and 100,000. A gene number of 70,000 would give a total coding sequence of 85 Megabases, less than 3% of our genome. Herein lies one of the major problems. A 3% return on investment, even when genes are identifiable, is rather poor, especially when sequencing is an expensive business. As if that's not enough, a large percentage of highly re-iterated dispersed repeats serve to exacerbate the problem.
- Fluorescence in situ hybridization of C3 and 18S rDNA to horse chromosomes
Abstract Fluorescence in situ hybridization (FISH) was used to localize equine C3 and nucleolus organizer regions (NORs). A 4.3 kb human C3 probe and a 2 kb mouse 18S rDNA probe were labeled with biotin and hybridized to horse chromosomes. Hybridization was detected by two layers of fluorescein-avidin and visualized with a laser scanning confocal microscope. Ongoing work in our laboratory provisionally maps the equine C3 to the telomeric region of the short arm of a midsize metacentric chromosome. Hybridization of the 18S probe confirms the number of equine NORs.
- Fugu Project Protocols
- Gene Discovery
An important stage in the biological interpretation of the sequence generated by the Human Genome Project is the identification of all the genes. Gene discovery at the Sanger Centre is a multidisciplinary project that has been set up to facilitate the definition of complete gene structures from genomic sequence. So far we have carried out pilot projects on a few selected regions of sequence determined either in-house or by our collaborators, in order to evaluate the most appropriate methods, resources and strategy.
- Gene Disruptions using P transposable elements: An integral component of
Biologists require genetic as well as molecular tools to decipher genomic information and ultimately to understand gene function. The Berkeley Drosophila Genome Project is addressing these needs with a massive gene disruption project that uses individual, genetically engineered P transposable elements to target open reading frames throughout the Drosophila genome. DNA flanking the insertions is sequenced, thereby placing an extensive series of genetic markers on the physical genomic map and associating insertions with specific open reading frames and genes. Insertions from the collection now lie within or near most Drosophila genes, greatly reducing the time required to identify new mutations and analyze gene functions. Information revealed these studies reveal about P element site specificity is being used to target the remaining open reading frames.
- Gene expression group
Aims To develop, improve and implement technologies for gene finding and expression profiling To generate data on tissue and cell-specific expression patterns of mammalian genes To use this information in order to further understand gene function within the context of sites of expression To correlate gene expression with the regulation of transcription To identify genes that might act as novel therapeutic targets
- Genetic Map of Caulobacter crescentus
The map is depicted in four segments which forms a single continuous linkage group as defined by RP-4 mediated conjugation(4), bacteriophage CR30 mediated transduction (15) and pulsed field gel electrophoresis (11,13). The numbers (in kilobases) indicate the approximate position of selected genes. Parentheses indicate that the precise location of the gene relative to adjacent genes is not known. Preceding * indicates that the relative orientation of the gene cluster is not known. ] after the gene indicates continuous genes.
- Genetic mapping of mutations in the zebrafish
A large number of developmental mutants of the zebrafish have been isolated in a recent mutagenesis screen (Haffter et al., 1996a; Haffter et al., 1996b). Our aim is to place 665 of these mutations on a simple sequence length polymorphism map as a first step towards molecular analysis. For our project we have selected 182 SSLP markers (Knapik, E. W. et al. (1996) Development 123, 451-60; Goff, D. J. et al. (1992) Genomics 14, 200-2) that give strong and easily distinguishable PCR products when amplified from the Tü line, in which the mutagenesis was done, and from the newly established reference line WIK (available from the Tübingen stockcenter).
- Genetics
Mining Co.
- Genetics and Evolution of Transposable
Elements
The long term theme of this research is to identify and understand the genetic and evolutionary factors that determine the distribution and abundance of transposable elements among species. We propose to exploit novel features of the Drosophila transposable element mariner in order to define genetic factors that control transposition and excision. The mariner element is active in somatic cells, so that excision, and to lesser extent transposition, can be followed phenotypically. The phenomenon of greatest immediate interest is inherited somatic mosaicism, in which an autonomous copy of mariner results in a high frequency of excision of all mariner elements, including a reporter element inserted in the white-peach allele. Thus, the mariner system is the first in Drosophila that provides the kinds of phenotypic indicators that have proven so powerful in the analysis of transposable elements in maize.
- Genetics Education Center (University of Kansas Medical Center)
For educators interested in human genetics and the human genome project
- Growth Factors and Conditions for Epithelial Cell Growth
Imaginal disc epithelia represent a defined epithelial cell population. Cell lines from these tissues allow us to look at factors that may control epithelial cell growth and also allow us to analyze aspects of the cell biology of overgrowth mutants in vitro. Imaginal disc cell lines grow in a culture medium consisting of Shields and Sangs M3 supplemented with 2% FCS, insulin and a fly extract. These additives allow growth to occur. When these cells are grown in serum free medium, cells decrease in number, become round and flattened. Collecting conditioned medium and using this as a supplement had quite a different effect. The cells elongated, migrated and grew. It appears that conditioned medium (CM) contains growth factors that stimulate growth of the cells in serum free medium and alter their behaviour. Analysis of this conditioned medium should allow us to isolate new growth promoting factors from Drosophila. Partial purification showed that one fraction maintained the biological activity but at a lower level than native CM. That level of activity could be supplemented by the addition of the low molecular weight fraction (<10kD) from native CM. Thus it appears the cell growth promoting activity of partially purified CM requires a low molecular weight co-factor. We are currently purifying and identifying this material.
- Growth Factors and Oncogenes
Although the MRFs positively activate the myogenic program, the activity of these proteins is tightly regulated through a growth factor-mediated signal transduction cascade. MRF-expressing cells maintained in a serum-free medium rapidly differentiate by transcriptionally activating muscle structural genes. Differentiation is inhibited, however, when the serum-free medium is supplemented with purified growth factors such as fibroblast growth factor-2 (FGF-2) or transforming growth factor-b (TGF-b). A similar inhibition of activity also is observed when the muscle regulatory factors are co-expressed in cells containing high levels of several oncogenes such as c-myc, H-ras and c-jun. Understanding how these diverse growth control agents inhibit the MRF proteins from transcriptionally activating various structural genes is a major goal of the Konieczny and Taparowsky laboratories. Current studies are focused on examining how specific phosphorylation events regulate the ability of the MRFs to dimerize with other bHLH proteins, to bind to DNA and to function as transcriptional activators (Mol. Cell Biol., 1995, 15:5205-5213; Mol. Cell Biol., 1996, 16:1604-1613). In addition, we are dissecting the individual pathways by which the G protein Ras functions to repress myogenesis (Mol. Cell Biol., 1997, 17:3547-3555). Recently, we have found that an additional Ras pathway, distinct from the well characterized MAP kinase and Rac/Rho pathways known to be important for the transforming function of activated Ras, is primarily responsible for the inhibition of myogenesis by H-Ras. Understanding the signal transduction pathways that negatively and positively regulate the activity of these novel transcription factors should provide a critical view as to how growth factors and oncogenes control these important developmental decisions.
- Growth factors in the treatment of degenerative retinal disorders.
There are currently a number of degenerative conditions, both inherited and acquired, that affect the retina and lead to blindness. Retinal photoreceptors degenerate from inherited conditions, such as retinitis pigmentosa or as a result of light damage or normal ageing; retinal ganglion cells degenerate from optic nerve injury or glaucoma. Current research in this field includes the use of growth factors to: (1) inhibit the degenerative processes; (2) promote regeneration of the retina from the pigmented epithelium; and (3) improve the conditions for transplantation of new cells to the retina by expanding the photoreceptor cell populations in vitro. The results to date have shown that a number of different growth factors promote survival of retinal cells in vitro and in vivo. In addition, some of the same factors can stimulate regeneration in the developing retina and act as mitogens for the retinal progenitor cells. It is likely that a combination of these approaches will ultimately be important for the treatment of the various retinal degenerations.
- Homologs of the wts gene
- How were the cDNA libraries madeNULL
We have produced two new full length cDNA libraries: the GH adult head library and the LP larval and early pupal stage library. Since many of the HL adult head library clones were not full length, and others lacked inserts, we chose to remake this library. We are currently sequencing from these libraries.
- Human Chromosome 1 Project
Human Chromosome 1 Project Chromosome 1 is the largest human chromosome and comprises approximately 300Mb of DNA (approximately 10% of the human genome). Our aim, in close collaboration with the chromosome 1 community, is to construct a comprehensive map of human chromosome 1, including all genes and other biologically important sequences, up to the level of the DNA sequence itself.
- Human Chromosome 10 Project
Human Chromosome 10 Project The human chromosome 10 is approximately 144 Megabases in length. Our aim is to map and sequence this entire chromosome in collaboration with the chromosome 10 community.
- Human Chromosome 13 Project
Our aim is to map and sequence this entire chromosome in collaboration with the chromosome 13 community.
- Human Chromosome 20 Project
Chromosome 20 comprises approximately 72 Mega bases of DNA. Our aim is to construct a comprehensive map of human chromosome 20 including all genes and other biologically important sequences, up to the level of the DNA sequence itself in close collaboration with the chromosome 20 community.
- Human Chromosome 22 Project
Human chromosome 22 is a small acrocentric chromosome, and comprises approximately 53Mb of DNA. The p arm contains ribosomal RNA genes. The q arm is relatively G+C rich and may therefore be gene rich. Our aim is to construct a comprehensive map of human chromosome 22 including all genes and other biologically important sequences, down to the level of the DNA sequence itself. Mapping and sequencing is being undertaken by an international consortium. We hae also recently started gene finding and polymorphism projects centred around chromosome 22.
- Human Chromosome 6 Project
The human chromosome 6 is estimated to be 150-180 Mb in size. It is probably best known for encoding the Major Histocompatibility Complex (MHC) which is essential to the human immune response. The MHC spans about 4 Mb on the short arm of the chromosome (6p21.3) and a coordinated effort to sequence the entire region is well underway. Chromosome 6 is also believed to encode genes involved in genetic diseases including arthritis, diabetes, haemochromatosis, schizophrenia and many more. Our aim is to map and sequence this entire chromosome in close collaboration with the chromosome 6 community.
- Human Chromosome 9 Project
Human Chromosome 9 Project The human chromosome 9 is approximately 145 Megabases in length. Our aim is to map and sequence this entire chromosome in collaboration with the chromosome 9 community.
- Human Radiation Hybrid Mapping
Human Radiation Hybrid Mapping As part of the Radiation Mapping Consortium we aim to generate a radiation hybrid (RH) transcript map of the human genome that positions Expressed Sequence Tags (ESTs) relative to other informative markers (e.g. microsatellites). A set of approximately 1100 genetic markers from the Genethon genetic map, used in common with the other groups, has been used to construct the framework maps and to form the basis for map integration. The first release of the Gene Map in 1996 reported ~16,000 genes. The consortium has now released the 1998 Gene Map which features 30,181 genes.
- Human Sequencing Collaborations
A primary aim in setting up the Sanger Centre was to play a major part in sequencing the human genome. Our policy is to make sequence and related map information available as early as possible to the biological community. Current sequencing projects are listed below, with access to further information including maps, status tables and sequence. Information and sequence for individual clones is also accessible by name through a Web form. Sequences and status tables can also be obtained from our ftp site.
- Human X Chromosome Project
The human X chromosome consists of 160 Mb of DNA, or approximately 5% of the human genome. Our goal is to map and sequence large regions of the X chromosome and to decode the biological information they contain.
- Identification of syntenic groups in the horse using RAPD markers and a somatic
One step in developing a map of the equine genome is to establish a foundation physical map. Random amplified polymorphic DNA markers (RAPDs) (Williams et al, 1990) can be used with a panel of somatic cell hybrids to establish markers which can later be tested for synteny. One RAPD primer usually yields more than one marker and the number of RAPD primers available is virtually unlimited, so many markers can be quickly identified.
- IFBM Institut für Biologie und Medizin, Köln
Laborfortbildungskurse in Molekularbiologie und Gentechnik, Molekularer Medizin, Zellkultur und Elektrophoresetechniken.
- Inverse PCR and Cycle Sequencing Protocols
For recovery of
Inverse PCR and Cycle Sequencing Protocols For recovery of sequences flanking PZ, PlacW and PEP elements
- IPK Gatersleben: Mansfeld-Server: IPK Projects
Welcome to the Mansfeld Server of the IPK Gatersleben: IPK Projects
- Isolation of mRNA from Drosophila rough endoplasmic reticulum
This protocol has been used to produce an RNA sample at least 10-fold enriched for mRNAs encoding membrane and secreted proteins versus cytosolic proteins (C. C. Kopczynski, T. Serrano, G. R. Rubin, and C. S. Goodman, in preparation).
- It's All in the timing; Imitiation and Maintenance of Homeotic
Gene Expression
The homeobox gene pal-1 functions in the V6 seam cell to prevent signals from neighboring cells from inhibiting mab-5 function in V6 (Waring and Kenyon 1990;1991). In both mab-5 and pal-1 mutants V6 generates a lineage similar to V1 -V4,producing alae instead of rays. V6 will make rays in pal-1 mutants if seam cells adjacent to V6 are ablated or if mab-5 activity is provided by the mab-5 gain-of-function allele e1751 .Steve Salser (see this WBG) has shown by immunofluorescence antibody staining that, unlike in WT, in pal-1 ( e2091 ), mab-5 protein is not expressed in V6 at hatching; a mab-5 -lacZreporter gene is also not expressed in V6 in the embryo. The current model is that signals between seam cells inhibit mab-5 expression in the seam cells and that pal-1 functions in V6 to overcome or bypass this inhibition.
- Karyotype variation
When different isolates of Candida albicans are compared, the most frequently observed karyotype variation is the change in size of chromosome R described on the chromosome numbering page. Three other types of chromosome variation are commonly encountered: translocations, chromosome fragments, and aneuploidy. These are described in the sections below
- Lernzirkel Genetik
Der Lernzirkel Genetik wurde an der Akademie für Lehrerfortbildung und Personalführung in Dillingen (Bayern) konzipiert und danach für die Verwendung im Unterricht aufbereitet. Dabei entstand zusätzlich zu den Dokumenten für Word, die in der ausgedruckten Form die übliche Arbeitsgrundlage für den Unterricht darstellen, auch eine virtuelle Version für Browser, die u. a. zum Selbststudium herangezogen werden kann. Zielgruppe für die zu bearbeitenden Grundlagen der Genetik sind die Schüler der 9. Klasse Gymnasium (Bayern) und der 10. Klasse Realschule (Bayern).
- LifeScience.de LifeScience.de - das Online-Magazin über die Welt der Bio- und Gentechnologie
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- Localization of bicoid mRNA in Drosophila embryos
The anterior pole of the Drosophila embryo is determined already during oogenesis by the localization of the maternal bicoid mRNA which is mainly produced in the nurse cells, transported to the oocyte and localized to the anterior pole. As a result, a bicoid protein gradient with its highest concentrations at the anterior pole is generated through translation from the localized source shortly after fertilization. The protein acts as a transcription factor that activates several target genes, thereby creating a basic differential gene expression pattern which subsequently will be further refined.
- Maternal mutant screen in the zebrafish
The earliest patterning events in vertebrate embryogenesis are still poorly understood. In lower vertebrates, these events are initiated by maternal factors present in the egg (such as involved in bicoid localization in Drosophila). In order to identify genes coding for such factors, we are carrying out a screen for maternal-effect mutations in the zebrafish. Mutations are induced in the germ line of parental (P) males by exposing them to the point-mutagen N-ethyl-N-nitroso-urea (ENU). P males are then mated to produce F1 progeny heterozygous for the induced mutations. Eggs are stripped from the F1 females and gynogenesis is artificially induced using early pressure, which inhibits the second meiotic division of the egg. This allows mutations to become homozygous in the gynogenetic F2 generation. Finally, F2 adult females are screened for maternal-effects by crossing them to wild type males and testing their progeny for embryonic phenotypes.
- Maternal mutants in Drosophila
In Drosophila, large scale mutagenesis screens have revealed genetic components required maternally for the establishment of the embryonic axes. Four groups of genes act in a largely independent manner to specify the antero-posterior and the dorso-ventral axis, as well as the terminal regions of the embryo. In total, about 30 genes whose products are essential for pattern formation during oogenesis have been identified by maternal-effect mutations. Although most of the components involved in axis formation have probably been found by this approach, several genetic and biochemical arguments suggest that certain genes have escaped detection in the classic screens. These screens allowed the isolation of mutations only in genes whose function is strictly maternal: genes which also have an essential function at other developmental stages could not be identified. Also, based on the obtained allele frequencies, the screens did not reach saturation.
- Mechanisms of cell determination in Drosophila
A crucial part of the process of cell determination (the acquisition of specific cell fates during development) is the activation of homeotic genes in some but not all primordia in the early embryo. Homeotic genes act throughout development to control proper patterning of various structures derived from these primordia, and thus the active state of homeotic genes has to be maintained through subsequent cell divisions as the primordia grow. Similarly, in those primordia where particular homeotic gene products are not wanted, these genes must remain inactive.
- Mesoderm and gastrulation
We are interested in the source of mesoderm inducing signals in the early fish blastula and are using experimental embryology to adress this issue. A main focus of the lab is the analysis of mutants which exhibit a dorsalized or ventralized phenotype. We have shown that the dino and swirl mutant phenotypes (Hammerschmidt, 1996a; Mullins, 1996) are caused by mutations in the chordino and the zBMP2 gene respectively (Schulte-Merker et al., 1997; Kishimoto et al., submitted), and are currently analysing these and other mutants. The aim of all these studies is to elucidate which maternal and zygotic factors pattern the early zebrafish embryo.
- Methoden für die Mol Methoden und Resourcen in Molekularbiologie und Biomedizin
Die wissenschaftliche Info-Seite für die Bereiche Molekularbiologie und Biomedizin mit umfangreicher molekularbiologischer Methodensammlung, biologischen Internet-Links, Zugang zu Datenbanken, Laborprotokollen und kostenfreiem Medline-Zugang Die Seite ist bilingual gestaltet (Deutsch / English)
- Mist1: a Novel bHLH Factor
Previous studies in the lab have confirmed that bHLH factors, such as members of the MyoD family of proteins, play critical roles in regulating both gene transcription and cell fate determination. Our studies also have demonstrated that active and negative strategies are involved in controlling the establishment and maintenance of a particular phenotype. In order to better understand how bHLH proteins interact and regulate each other's activities, we recently utilized a yeast one-hybrid screening strategy to identify an additional member of the complex bHLH protein network, Mist1 (DNA and Cell Biology, 1996, 15:1-8). Mist1 exhibits a complicated expression pattern with transcripts being detected in several different cell derivatives (Dev. Biol., 1997, 182:101-113). In the mesoderm, Mist1 transcripts are expressed in all skeletal muscle forming regions during embryonic days E12.5 and E16.5.
- Mitochondrial Genome
- Mitose und Meiose
Ablauf und Bedeutung von Mitose und Meiose können mit Hilfe dieses Repetitoriums im Selbststudium erarbeitet werden. Primäre Zielgruppe sind die Schüler der Mittelstufe, doch bietet sich die Verwendung auch im Rahmen einer Wiederholung der Lerninhalte zur Zellteilung in der Kollegstufe, der beruflichen Oberstufe oder der Erwachsenenbildung an.
- Mitosis and Meiosis
This self-guided study of mitosis and meiosis has been developed as a refresher course with its sequences being accessible by mouse clicks on the underlined stages shown in the index frame. Further pages containing high resolution figures can be printed out by the browser additionally. Although students at high school level may be the primary target for this self-guided study which is also available on CD, it could serve as well as a motivating tool in providing undergraduates and people in adult education with information on the significance and the individual phases of mitosis and meiosis.
- MLP, a Muscle LIM Protein
A large family of proteins recently has been identified that contains a cysteine-rich structural motif consisting of the sequence (CX2CX16-23HX2C)-X2-(CX2CX16-21CX2C/H/D). This motif is known as a LIM domain due to its presence in three developmentally important transcription factors; Lin-11, Isl-1 and Mec-3. The LIM domain is a zinc-binding structure that coordinates two atoms of zinc in a tetrahedral fashion via the conserved cysteine and histidine residues in the LIM consensus. One such LIM protein, referred to as MLP for muscle LIM protein, is expressed exclusively in skeletal and cardiac muscles, localizes to discrete cell compartments in the nucleus and cytoplasm and has been found to promote muscle differentiation. Overexpression of MLP in C2C12 myoblasts enhances skeletal myogenesis, whereas inhibition of MLP activity blocks terminal differentiation. Thus, MLP functions as a positive developmental regulator, although the mechanism through which MLP promotes terminal differentiation events remains unknown.
- Mologen
Our areas of competence are gene expression, gene therapy and bioinformatics. We are dedicated to the development of DNA expression and delivery technologies for human and veterinary applications, leading to products for gene therapy, and prophylactic and therapeutic DNA-based vaccines.
- Mutations affecting midline signaling in the zebrafish
Signals from the vertebrate midline have for a long time been implicated in patterning the paraxial mesoderm and the ventral neural tube. In the zebrafish, a number of mutations affecting the midline have been described. Among these are mutations affecting formation of the notochord, mutations affecting somite patterning and mutations affecting the ventral neural tube. Mutations in six genes affect the formation of the horizontal myoseptum, which in the wildtype separates the somites into a ventral and a dorsal part. This class of mutants, termed the you-type mutants, forms U-shaped instead of V-shaped somites. Earlier in development, these mutants are affected in the adaxial cells and the muscle pioneers. The similarity of the somite phenotype in mutants lacking the notochord and in the you-type mutants suggests that the you-type genes are involved in a signaling pathway from the notochord involved in patterning the somites.
- Neural crest development
The neural crest provides a population of pluripotent, highly migratory cells which delaminate from the neuroepithelium and differentiate into a wide range of cell types. Neural crest cells originate from the mid- and hindbrain and migrate ventrally to populate the developing head. Once they have reached their targets they differentiate into cartilage, connective tissue, sensory neurons and pigment cells. Although neural crest development has been studied for some time by elegant embryological and in vitro studies very little is known about the genes which regulate this process. As neural crest cells are one of the few vertebate cell types which have no clear analogue in invertebrate species, it is more difficult to apply results from genetic screens in Drosophila and C.elegans to this problem. We are currently using mutants isolated in a large scale zebrafish screen to identify and, eventually, molecularly characterise genes involved in neural crest development in vivo.
- Neural crest induction, cell migration, cell adhesion &
cytoskeletal
Background: Neural crest is a tissue unique to vertebrates and forms at the boundary of the epidermis and neural tube. Neural crest cells delaminate from the neuroepithelium and then migrate and differentiate into a number of different cell types. Cranial neural crest cells, for example, migrate to form a substantial proportion of the bones and cartilages of the skull and face. Defects in neural crest formation, migration or differentiation, collectively known as neurocristopathies, underlie a number of severe birth defects. The formation of the neural crest involves the remodeling of cell-cell and cell-matrix attachment molecules and the reorganization of the cytoskeleton to support cell migration. We are particularly interested in the initial aspects of this process, that is how neural crest is induced and the nature of the changes in cell organization associated with its migration.
- Neurogenetik-Online
Dies ist das vollständige und bebilderte Neurogenetik-Kapitel des Lehrbuchs für Genetik des Gustav-Fischer Verlags (Seyffert et al.).
- biokurs Online Biologiekurs
Online Biologie Lernsystem für Schüler und Studenten: Glossare, Stichwortlisten, Automat. Tests, Links, biomoleküle in 3D
- Overview
The human genomic research programme at the Sanger Centre encompasses mapping, sequencing, and structural and functional interpretation. Some groups work on specific chromosomes. Others are devoted to whole genome mapping, developing resources, or automation, data-handling and analysis. Additional groups are involved in discovering ways of analysing sequences, comparisons with other genomes, studying the structure and expression of genes, identifying polymorphisms, and examining chromatin structure in relation to function. These studies will contribute to the annotation of the human genome sequence and ultimately will provide a detailed and informative picture of the human chromosomes, genes and their biological function.
- P1 Vectors
Two types of P1 vectors The P1 mapping library consists of clones generated in two related P1 cloning vectors. 3,840 clones were inserted into the vector known as pNS583tet14Ad10 (Smoller et al. 1991) and 5,376 clones were from the ligation mixture using the vector called pAd10sacBII (Kimmerly et al. 1996). Both vectors contain genes that allow resistance to the antibiotic kanamycin, a plasmid origin of replication that provides for a single copy, a loxP site (the cis-acting site specific recognition signal for the P1 recombinase), and a gene that allows resistance to tetracycline. Inserts cloned in the vector pNS583tet14Ad10 have been introduced into the BamHI site in the gene allowing tetracycline resistance. A sacBII cassette was introduced by Sternberg (1990) as a means of selecting for clones with inserts. The cloned inserts in this vector system are introduced between SP6 and T7 RNA polymerase promoters that are positioned of the Bacillus subtilis genes found in the SacBII cassette. The sequences between the loxP sites (containing the Ad10 sequences) are deleted during library construction and thus are not present when the clones are mapped and eventually sequenced.
- Polymorphisms from Genomic Sequence
Summary We propose to define sequence polymorphisms in human genomic DNA for use in genetic analysis. All types of sequence variant will be annotated, and biallelic single- base substitutions will be assayed in a limited population to assess the degree of polymorphism.
- pOT2 Vector
he pOT2 vector was constructed by Oroon Hubbard, and was designed to give optimal results for transposon mapping and sequencing efforts. It is comprised of Mike Strathmans's pCSOS-r, with a modified pSP72 polylinker cloned into SalI and PstI sites. The pOT2 vector carries the Chloramphenicol resistance gene and is 1.50kb in size.
- Radiation hybrid mapping of cDNAs, ESTs and SSLPs in the zebrafish
A whole-genome radiation hybrid panel for the zebrafish was generated by the lab of P. N. Goodfellow by fusing an irradiated zebrafish donor cell line with a recipient hamster cell line (Kwok, C. et al. (1998) Nucleic Acids Res 26, 3562-6). Random fragments of the zebrafish chromosomes are integrated into the hamster chromosomes or retained as separate minichromosomes. The radiation-induced breakpoints in the zebrafish genome can be used for mapping in a manner analogous to recombination breakpoints in a genetic mapping approach. However, in the radiation hybrid approach the breakage frequency is higher, allowing higher resolution, and map distances more closely reflect actual physical distances. Almost any amplifiable sequence can be scored for its presence or absence in the hybrids, without a need for polymorphism.
- Repeated DNA
A number of repeated DNA sequences have been identified in Candida albicans. Several have been used as probes in epidemiologic studies. The relationships between all of the gene families have not been established; however, in some cases, partial DNA sequence or hybridization data are available
- Research Overview
Our laboratory is interested in understanding the molecular regulatory circuits that function during vertebrate development. A basic premise of development is that sets of genes need to be precisely controlled at the transcriptional level to establish the correct specification and differentiation of tissue types and organ systems. Transcriptional regulation involves not only the ability to turn genes on or off, but also the ability to ensure that genes are expressed in a correct positional, temporal and quantitative fashion. An ideal model system in which to study the molecular regulation of gene expression is skeletal muscle development. All vertebrate muscles are derived from precursor cells (myoblasts) that colonize regions of the embryo, fuse into multinucleate myotubes and transcriptionally activate muscle-specific genes. Interestingly, this entire process is tightly regulated through signal transduction pathways that initiate extracellularly and that culminate in the transcriptional activation or repression of specific genes.
- RNO 1
- RNO 10
- RNO 11 Physical map
- RNO 12 Physical map
- RNO 13 Physical map
- RNO 14 Physical map
- RNO 15 Physical map
- RNO 16 Physical map
- RNO 17 Physical map
- RNO 18 Physical map
- RNO 19 Physical map
- RNO 2 Physical map
- RNO 20 Physical map
- RNO 3 Physical map
- RNO 5 Physical map
- RNO 6 Physical map
- RNO 7 Physical map
- RNO 8 Physical map
- RNO 9 Physical map
- RNO X Physical map
- Screening CK cDNA Clones by RNA In Situ Hybridization
The RNA in situ procedure described below is based on the protocol developed by Tautz and Pfeifle (Chromosoma 98 (1989), p81), but adapted to allow the screening of 96 RNA probes on whole-mount Drosophila embryos at the same time.
- Six Members of the MAGUK Gene Family are Expressed in Mammary Gland Tissue
- Somite formation in the zebrafish
Somites are segmentally repeated mesodermal structures within the vertebrate embryo that give rise to the vertebrae and muscle of the trunk and tail. A recent large-scale screen for developmental mutants of the zebrafish, Danio rerio, identified mutations in five complementation groups that affect the anterior-posterior pattern of the somites: fused somites (fss), beamter (bea), after eight (aei), deadly seven (des) and white tail (wit). Both embryological and molecular genetic techniques are being used to further characterize the role that fss, bea, aei, and des play in somitogenesis and to identify the affected genes. Moreover, cross-species experiments will be used to elucidate the extent of any evolutionary conservation of the regulatory networks involved in segmentation. Thus, this analysis is aimed at both understanding the mechanism by which the paraxial mesoderm is segmented in the zebrafish and determining the extent of conservation between species of genetic regulatory networks involved in segmentation.
- Summary of targets
Summary of targets Main projects Work is in progress on the following five chromosomes. Selected regions are the subject of early effort as listed, but further mapping and clone isolation is under way for the majority of each chromosome. See individual project pages for further information. These regions of Chromosomes 22 and X are being sequenced jointly with Genome Sequencing Centre, St Louis.
- Targeting of Membrane-Associated Guanylate Kinases (MAGUKs)
- Temporal and spatial pattern of MASH-1 expression in the developing rat
The temporal and spatial pattern of mammalian achaete-scute homolog 1 (MASH-1) expression in the developing rat retina was examined in an effort to correlate achaete-scute homolog expression with the generation of particular cell classes. The expression of MASH-1 was restricted to the latter portion of retinal neurogenesis and was most closely correlated with the appearance of bipolar cells and Muller glia, two cell classes that are generated late in retinogenesis. We also examined the proliferative nature of the MASH-1 -expressing cell type to confirm that MASH-1 is expressed by progenitor cells and to determine the proportion of the proliferating population that expresses MASH-1. MASH-1 was expressed by only 10-30% of the total proliferating population, depending on the age examined. Thus, MASH-1 expression provides a molecular marker of heterogeneity among retinal progenitor cells and may play a role in the commitment and/or differentiation of one or more of the late-appearing retinal phenotypes.
- The C. elegans Genome Project
The C. elegans Genome Project The C. elegans sequencing project is a collaboration between the Sanger Centre, Hinxton Hall, Cambridge and the Genome Sequencing Center at the Washington University School of Medicine, St. Louis.
- The Dictyostelium Genome Sequencing Project
The organization and funding to sequence the genome of Dictyostelium discoideum are now in place. The goal is to complete the 34 Mb sequence of this eukaryotic microorganism in the next few years by combining the efforts of an international consortium. High resolution physical maps of the 6 chromosomes and an ordered array of large inserts carried in yeast artificial chromosomes (YACs) are available to assist in the assembly of contiguous sequences (contigs) (Kuspa and Loomis 1996). An Expressed Tag Sequencing (EST) project carried out in Japan over the last few years has single-pass sequenced portions of over 8,000 cDNAs from developing cells and uncovered about 1,000 new genes that can form seeds for the generation of contigs. Large scale genomic sequencing projects have recently started at the Institute for Molecular Biotechnology, Jena, Germany and the Baylor Sequencing Center, Houston, Texas and will soon be joined by efforts at the Sanger Centre, Cambridge, England. The interest in the genome of this non-pathogenic organism is primarily to complement on-going molecular genetic studies that aim to define the roles of developmental genes during morphogenesis of multicellular organisms. Dictyostelium is a soil amoeba that shares many of the physiological functions seen in mammalian cells such as directed amoeboid movement, cell-cell adhesion, tissue differentiation, proportioning, and sorting (Loomis 1975; 1996; Maeda et al. 1997). It also shares properties with plant cells such as vacuolization and cellulose deposition during terminal differentiation of stalk cells. All the genes responsible for these processes will become available when the genome is sequenced.
- The Jackson Laboratory Backcross DNA Panel Mapping
Resource
The BC Panel Mapping Resource maintains and distributes small aliquots of DNA from panels of 94 backcross animals from the cross (C57BL/6J x M. spretus) x C57BL/6J, called BSB panel 1, and a similar BSS panel 2 made up of DNA from the reciprocal backcross (C57BL/6JEi x SPRET/Ei) x SPRET/Ei. We are providing these DNAs in microtiter format to other investigators interested in mapping loci using this densely marked mapping cross resource. We provide technical support for defining the necessary polymorphisms by PCR, and once these are defined, we ship the backcross DNAs as 125 ng/ul aliquots to be diluted for use as PCR templates for mapping experiments. If Southern blotting is the only mapping option, please contact us for further discussion.
- The Role of the Genome Project in Determing Gene Function: Insights
Large amounts of data, from DNA sequences to on-line brain atlases, are rapidly accumulating in public databases, and there is a heightened expectation that the increasingly powerful computer analyses of integrated databases will be sufficient to take us from DNA sequence to biological function. To what extent is this likely to be the caseNULL We have examined this question by considering: gene number in different evolutionary lineages; data derived from mutagenesis and gene knockouts in Drosophila melanogaster, Caenorhabditis elegans, Danio rerio, Mus musculus, Arabidopsis thaliana and Saccharomyces cerevisiae; gene regulatory dynamics in different systems; the utility of gene transfer methods that allow precisely controlled misexpression of genes; and the extent to which various processes are conserved between organisms in different lineages.
- The Wnt Gene Family in Mammary Gland Develop
The purpose of this review is to consider the involvement of Wnt proteins in mammary gland development. Advances in Wnt biology that are derived from studies of other systems are summarised in the reviews indicated. Historical Perspective The prototype member of the Wnt gene family, Wnt-1 (formerly known as int-1) was first isolated as a common site of integration by the mouse mammary tumour virus (MMTV) and was later shown to be homologous to the Drosophila segment polarity gene wingless [1-3] . In mouse mammary epithelial cells, MMTV integration activates Wnt-1 by increasing transcription of Wnt-1 mRNA leading to increased (tumourigenic) levels of the normal Wnt-1 protein. Wnt-1 has been shown to be a member of a large gene family that is highly conserved through evolution (reviewed in [4-6] ) and Wnt gene products have been implicated in the control of numerous developmental processes such as axis formation in Xenopus embryos [7] , murine hindbrain and kidney development [8-11] . Biochemical studies of Wnt proteins in cell culture and in Drosophila have shown that Wnt polypeptides are glycosylated, secreted and associate with the cell surface/extracellular matrix [12-16] . Microinjection analyses in Xenopus have shown functional differences between Wnt family members and have shown that the determinants of Wnt-specificity are localised to the C-terminal half of the protein [17] . Genetic studies of wingless in Drosophila, have identified genes with related phenotypes and have ordered them into a Wingless signal transduction pathway (reviewed in [18] ).
- The Wnt/wingless signaling pathway
Current model of the wg/Wnt signaling pathway (reviewed in Nusse R, 1997; Cadigan 1997; included here are only later references) In cells not exposed to the wg signal (left), Arm levels are kept low through interactions with the protein kinase zw3 (GSK-3b) APC and Axin (Behrens J, et al., Itoh K et al., Hart MJ et al.). GBP is another GSK binding protein which down-regulates the pathway (Yost et al). The wg/Wnt signal (right) leads, through its receptor (members of the frizzled (Fz) family) and dishevelled (Dsh) to inactivation of zw3. As a consequence, Arm increases in concentration and can bind to TCF1/Lef-1/pangolin. This complex can activate nuclear target genes, including Ubx. Loss of APC in mammalian cells can also lead to a critical loss over Arm control, leading to cell transformation, most likely by activation of other target genes. In colon cancer, the c-myc gene is activated by loss of APC (He 1998) Recently, it has been shown that in the absence of the Wnt signal,TCF acts as a repressor of Wnt/Wg target genes (Brannon 1997, Bienz 1998 . Riese 1997; also in C. elegans Lin 1998)TCF can form a complex with Groucho (Roose 1998) and CBP (Waltzer 1998.) repressing gene transcription when Wnt signaling is inactive (Cavallo 1998) Arm can convert TCF into a transcriptional activator of the same genes.
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trendenz neues aus Forschung und Wissenschaft
- TUMOR SUPPRESSOR GENES FUNCTIONING IN THE HEMATOPOIETIC SYSTEM
Mutations of at least 20 known loci cause melanotic tumor formation and overgrowth of the lymph glands, which are the source of blood cells in the Drosophila larva. In this laboratory we have cloned two of these genes. The first one, air8, was shown to encode the ribosomal protein S6. This protein is phosphorylated in a cell-cycle-dependent fashion, and we speculate that the mutations cause tumorigenesis by interfering with the translation of specific messages involved in the control of blood cell growth and differentiation. We are now concentrating on l(2)88/10. In this mutant, in addition to melanotic tumor formation the blood cells invade and destroy other tissues including imaginal discs. This may be the first example of an invasive tumor caused by a single mutation. In l(2)88/10 mutant larvae the lymph gland shows progressive enlargement, melanization and disintegration. The cells in these abnormal glands are abnormally large. Histological sections of mutant larvae show a general disintegration of internal structures and a striking accumulation of blood cells around and inside the imaginal discs. At the same time the free blood cell count drops dramaticaly, indicating that most blood cells are engaged in invasion. The l(2)88/10 locus was identified by the position of a single P-element insertion. The P-element is inserted in the 5' untranslated region of a 1.6 Kb transcription unit, thereby causing an early transcriptional stop. The cDNA sequence contains a single large open reading frame encoding a novel 300 aa. protein. Northern hybridization experiments showed that the 1,6 kb. transcript is missing from the mutants. We are now using antibodies to investigate the expression and subcellular localization of the protein product.
- Tübingen Drosophila stock collection
The Tübingen Drosophila stock collection contains approximately 1700 stocks, mostly mutants isolated in our lab. Our stocklist is accessible through FlyBase: Stocklist in .csv format (comma-separated list) Stocklist in .rpt format (for import into PC databases) These files contain all Drosophila stocks currently maintained in the Nüsslein-Volhard lab, and replace the previously published list: Tearle, R., and Nüsslein-Volhard, C. (1987). Tübingen mutants and stock list. Dros Inf Serv 66, 198-269.
- Tübingen zebrafish stockcenter
The stockcenter keeps about 400 mutant lines of Danio rerio, which are publicly available for scientific research. In addition the stockcenter is participating in the mapping of mutants in the genome. In collaborations with scientists in the Tübingen labs, as well as other laboratories, the stockcenter collection of mutants is screened for various phenotypic traits not covered in the original screen.
- Vertebrate genome evolution and the zebrafish gene map
In chordate phylogeny, changes in the nervous system, jaws, and appendages transformed meek filter feeders into fearsome predators. Gene duplication is thought to promote such innovation. Vertebrate ancestors probably had single copies of genes now found in multiple copies in vertebrates and gene maps suggest that this occurred by polyploidization. It has been suggested that one genome duplication event occurred before, and one after the divergence of ray-finned and lobe-finned fishes. Holland et al., however, have argued that because various vertebrates have several HOX clusters, two rounds of duplication occurred before the origin of jawed fishes. Such gene-number data, however, do not distinguish between tandem duplications and polyploidization events, nor whether independent duplications occurred in different lineages. To investigate these matters, we mapped 144 zebrafish genes and compared the resulting map with mammalian maps. Comparison revealed large conserved chromosome segments. Because duplicated chromosome segments in zebrafish often correspond with specific chromosome segments in mammals, it is likely that two polyploidization events occurred prior to the divergence of fish and mammal lineages. This zebrafish gene map will facilitate molecular identification of mutated zebrafish genes, which can suggest functions for human genes known only by sequence
- Virtual Library: Genetics
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