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111.
A physical map of the mouse genome 总被引:1,自引:0,他引:1
Gregory SG Sekhon M Schein J Zhao S Osoegawa K Scott CE Evans RS Burridge PW Cox TV Fox CA Hutton RD Mullenger IR Phillips KJ Smith J Stalker J Threadgold GJ Birney E Wylie K Chinwalla A Wallis J Hillier L Carter J Gaige T Jaeger S Kremitzki C Layman D Maas J McGrane R Mead K Walker R Jones S Smith M Asano J Bosdet I Chan S Chittaranjan S Chiu R Fjell C Fuhrmann D Girn N Gray C Guin R Hsiao L Krzywinski M Kutsche R Lee SS Mathewson C McLeavy C Messervier S Ness S Pandoh P Prabhu AL Saeedi P 《Nature》2002,418(6899):743-750
A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy. 相似文献
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113.
Changing potency by spontaneous fusion 总被引:204,自引:0,他引:204
Recent reports have suggested that mammalian stem cells residing in one tissue may have the capacity to produce differentiated cell types for other tissues and organs 1-9. Here we define a mechanism by which progenitor cells of the central nervous system can give rise to non-neural derivatives. Cells taken from mouse brain were co-cultured with pluripotent embryonic stem cells. Following selection for a transgenic marker carried only by the brain cells, undifferentiated stem cells are recovered in which the brain cell genome has undergone epigenetic reprogramming. However, these cells also carry a transgenic marker and chromosomes derived from the embryonic stem cells. Therefore the altered phenotype does not arise by direct conversion of brain to embryonic stem cell but rather through spontaneous generation of hybrid cells. The tetraploid hybrids exhibit full pluripotent character, including multilineage contribution to chimaeras. We propose that transdetermination consequent to cell fusion 10 could underlie many observations otherwise attributed to an intrinsic plasticity of tissue stem cells 9. 相似文献
114.
Presley JF Ward TH Pfeifer AC Siggia ED Phair RD Lippincott-Schwartz J 《Nature》2002,417(6885):187-193
Cytosolic coat proteins that bind reversibly to membranes have a central function in membrane transport within the secretory pathway. One well-studied example is COPI or coatomer, a heptameric protein complex that is recruited to membranes by the GTP-binding protein Arf1. Assembly into an electron-dense coat then helps in budding off membrane to be transported between the endoplasmic reticulum (ER) and Golgi apparatus. Here we propose and corroborate a simple model for coatomer and Arf1 activity based on results analysing the distribution and lifetime of fluorescently labelled coatomer and Arf1 on Golgi membranes of living cells. We find that activated Arf1 brings coatomer to membranes. However, once associated with membranes, Arf1 and coatomer have different residence times: coatomer remains on membranes after Arf1-GTP has been hydrolysed and dissociated. Rapid membrane binding and dissociation of coatomer and Arf1 occur stochastically, even without vesicle budding. We propose that this continuous activity of coatomer and Arf1 generates kinetically stable membrane domains that are connected to the formation of COPI-containing transport intermediates. This role for Arf1/coatomer might provide a model for investigating the behaviour of other coat protein systems within cells. 相似文献
115.
Bubonic plague is transmitted to mammals, including humans, by the bites of fleas whose digestive tracts are blocked by a mass of the bacterium Yersinia pestis. In these fleas, the plague-causing bacteria are surrounded by an extracellular matrix of unknown composition, and the blockage depends on a group of bacterial genes known as the hmsHFRS operon. Here we show that Y. pestis creates an hmsHFRS-dependent extracellular biofilm to inhibit feeding by the nematode Caenorhabditis elegans. Our results suggest that feeding obstruction in fleas is a biofilm-mediated process and that biofilms may be a bacterial defence against predation by invertebrates. 相似文献
116.
The chemical repertoire of natural ribozymes 总被引:29,自引:0,他引:29
Although RNA is generally thought to be a passive genetic blueprint, some RNA molecules, called ribozymes, have intrinsic enzyme-like activity--they can catalyse chemical reactions in the complete absence of protein cofactors. In addition to the well-known small ribozymes that cleave phosphodiester bonds, we now know that RNA catalysts probably effect a number of key cellular reactions. This versatility has lent credence to the idea that RNA molecules may have been central to the early stages of life on Earth. 相似文献
117.
Constância M Hemberger M Hughes J Dean W Ferguson-Smith A Fundele R Stewart F Kelsey G Fowden A Sibley C Reik W 《Nature》2002,417(6892):945-948
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119.
Berger MF Lawrence MS Demichelis F Drier Y Cibulskis K Sivachenko AY Sboner A Esgueva R Pflueger D Sougnez C Onofrio R Carter SL Park K Habegger L Ambrogio L Fennell T Parkin M Saksena G Voet D Ramos AH Pugh TJ Wilkinson J Fisher S Winckler W Mahan S Ardlie K Baldwin J Simons JW Kitabayashi N MacDonald TY Kantoff PW Chin L Gabriel SB Gerstein MB Golub TR Meyerson M Tewari A Lander ES Getz G Rubin MA Garraway LA 《Nature》2011,470(7333):214-220
120.
Skarnes WC Rosen B West AP Koutsourakis M Bushell W Iyer V Mujica AO Thomas M Harrow J Cox T Jackson D Severin J Biggs P Fu J Nefedov M de Jong PJ Stewart AF Bradley A 《Nature》2011,474(7351):337-342
Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome. 相似文献