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1.
Human noroviruses (HuNoV) are a major cause of nonbacterial gastroenteritis worldwide, yet details of the life cycle and replication of HuNoV are relatively unknown due to the lack of an efficient cell culture system. Studies with murine norovirus (MNV), which can be propagated in permissive cells, have begun to probe different aspects of the norovirus life cycle; however, our understanding of the specific functions of the viral proteins lags far behind that of other RNA viruses. Genome-wide functional profiling by insertional mutagenesis can reveal protein domains essential for replication and can lead to generation of tagged viruses, which has not yet been achieved for noroviruses. Here, transposon-mediated insertional mutagenesis was used to create 5 libraries of mutagenized MNV infectious clones, each containing a 15-nucleotide sequence randomly inserted within a defined region of the genome. Infectious virus was recovered from each library and was subsequently passaged in cell culture to determine the effect of each insertion by insertion-specific fluorescent PCR profiling. Genome-wide profiling of over 2,000 insertions revealed essential protein domains and confirmed known functional motifs. As validation, several insertion sites were introduced into a wild-type clone, successfully allowing the recovery of infectious virus. Screening of a number of reporter proteins and epitope tags led to the generation of the first infectious epitope-tagged noroviruses carrying the FLAG epitope tag in either NS4 or VP2. Subsequent work confirmed that epitope-tagged fully infectious noroviruses may be of use in the dissection of the molecular interactions that occur within the viral replication complex. 相似文献
2.
Ralf J. Jäger Vincent R. Harley Rudolf A. Pfeiffer Peter N. Goodfellow Gerd Scherer 《Human genetics》1992,90(4):350-355
A familial mutation in SRY, the gene coding for the testis-determining factor TDF, was identified in an XY female with gonadal dysgenesis, her father, her two brothers and her uncle. The mutation consists of a T to C transition in the region of the SRY gene coding for a protein motif known as the high mobility group (HMG) box, a protein domain known to confer DNA-binding specificity on the SRY protein. This point mutation results in the substitution, at amino acid position 109, of a serine residue for phenylalanine, a conserved aromatic residue in almost all HMG box motifs known. This F109S mutation was not found in 176 male controls. When recombinant wildtype SRY and SRYF109S mutant protein were tested in vitro for binding to the target site AAC AAAG, no differences in DNA-binding activity were observed. These results imply that the F109S mutation either is a rare neutral sequence variant, or produces an SRY protein with slightly altered in vivo activity, the resulting sex phenotype depending on the genetic back-ground or environmental factors.This paper is dedicated by G. S. to Professor Ulrich Wolf on the occasion of his 60th birthday 相似文献
3.
4.
Geoffrey W. Krissansen Patricia A. Gorman Christine A. Kozak Nigel K. Spurr Denise Sheer Peter N. Goodfellow Michael J. Crumpton 《Immunogenetics》1987,26(4-5):258-266
The gene coding for the M
r 26000 chain of the human CD3 (T3) antigen/T-cell antigen receptor complex was mapped to chromosome band 11q23 by using a cDNA clone (pJ6T3 -2), by in situ hybridization to metaphase chromosomes and by Southern blot analysis of a panel of human-rodent somatic cell hybrids. The mouse homolog, here termed Cdg-3, was mapped to chromosome 9 using the mouse cDNA clone pB10.AT3 -1 and a panel of mouse-hamster somatic cell hybrids. Similar locations for the CD3
genes have been described previously. Thus, the corporate results indicate that the CD3
and genes have remained together since they duplicated about 200 million years ago. 相似文献
5.
6.
Evolutionary conservation of the human homologue of the yeast cell cycle control gene cdc2 and assignment of Cd2 to chromosome 10 总被引:3,自引:0,他引:3
Nigel K. Spurr Alan Gough Paul J. Goodfellow Peter N. Goodfellow Melanie G. Lee Paul Nurse 《Human genetics》1988,78(4):333-337
Summary The human homologue of the fission yeast Schizosaccharomyces pombe cell cycle control gene cdc2 has been assigned to chromosome 10. DNA hybridization reveals that this gene is highly conserved in vertebrates. The human CDC2 gene probe detects a simple two-allele polymorphism in Taq1-digested DNA. 相似文献
7.
Sefton Louise Arnaud Danielle Goodfellow Peter N. Simmler Marie-Christine Avner Philip 《Mammalian genome》1992,2(1):21-31
The irradiation and fusion gene transfer (IFGT) procedure provides a means of isolating subchromosomal fragments for use in the mapping of loci and for cloning probes from a particular area of a chromosome. Using this procedure, two large panels of somatic cell hybrids that contain mouse X Chromosome (Chr) fragments have been generated. These hybrid panels were generated by irradiating the monochromosomal mouse-hamster hybrid HYBX, which retains the mouse X Chr, with either 10 K or 50 K rads of X-irradiation followed by fusion with a recipient Chinese hamster cell line. IFGT hybrids retaining mouse material were generated at high frequency. These hybrids were used to orient loci in the X-inactivation center region that had not been resolvable in our interspecies backcross panel and also to map, within the terminal region of the X Chr, repeat elements detected by the probe p15-4. These hybrids not only complement existing interspecies meiotic mapping panels for the detailed analysis of specific regions of particular chromosomes, but also provide a potential source of material for chromosome-specific probe isolation. 相似文献
8.
The introduction of new technology and increased effort from around the world is driving the completion of the human gene map. In parallel with the creation of the map, we are beginning to see the bio-medical benefits that are a direct consequence of learning more about our own genome. 相似文献
9.
Kenneth H. Astrin Cecilia A. Warner Han-Wook Yoo Paul J. Goodfellow Shih-Feng Tsai Robert J. Desnick 《Human genetics》1991,87(1):18-22
Summary Uroporphyrinogen III synthase [UROS; hydroxymethylbilane hydro-lyase (cyclizing), EC 4.2.1.75] is the fourth enzyme in the human heme biosynthetic pathway. The recent isolation of the cDNA encoding human UROS facilitated its chromosomal localization. Human UROS sequences were specifically amplified by the polymerase chain reaction (PCR) from genomic DNA of two independent panels of human-rodent somatic cell hybrids. There was 100% concordance for the presence of the human UROS PCR product and human chromosome 10. For each of the other chromosomes, there was 19%–53% discordance with human UROS. The chromosomal assignment was confirmed by Southern hybridization analysis of DNA from somatic cell hybrids with the full-length UROS cDNA. Using human-rodent hybrids containing different portions of human chromosome 10, we assigned the UROS gene to the region 10q25.2 q26.3. 相似文献
10.
An investigation into the spatial distribution of hypolimnetic ciliates in three small eutrophic lakes during the period of summer stratification was carried out. Peak ciliate densities were found to occur at the oxic/anoxic boundary, ciliate numbers declining with increasing depth within the hypolimnion. The ciliates only occurred in aerobic water where oxygen levels were less than about 0.5 mgl–1 Laboratory experiments demonstrated that the ciliates swim upwards under anaerobic conditions but swim rapidly downwards under aerobic conditions. Further laboratory experiments showed that although the bulk of the population occured within anaerobic water, the hypolimnetic ciliates are aerobes and cannot survive indefinite anoxia. Despite the demonstrable toxicity of high levels of ammonia and sulphide, it was probably excesive distance from an available source of oxygen that excluded the ciliates from the lowest levels of the hypolimnion. Possible mechanisms which allowed these aerobic ciliates to colonise anaerobic water are considered. 相似文献