排序方式: 共有11条查询结果,搜索用时 722 毫秒
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Hillier LW Graves TA Fulton RS Fulton LA Pepin KH Minx P Wagner-McPherson C Layman D Wylie K Sekhon M Becker MC Fewell GA Delehaunty KD Miner TL Nash WE Kremitzki C Oddy L Du H Sun H Bradshaw-Cordum H Ali J Carter J Cordes M Harris A Isak A van Brunt A Nguyen C Du F Courtney L Kalicki J Ozersky P Abbott S Armstrong J Belter EA Caruso L Cedroni M Cotton M Davidson T Desai A Elliott G Erb T Fronick C Gaige T Haakenson W Haglund K Holmes A Harkins R Kim K Kruchowski SS Strong CM Grewal N Goyea E 《Nature》2005,434(7034):724-731
Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions. 相似文献
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Physiological [Ca2+]i level and pump-leak turnover in intact red cells measured using an incorporated Ca chelator 总被引:14,自引:0,他引:14
The physiological actions of Ca2+ as a trigger and second messenger depend on the maintenance of large inward resting Ca2+ gradients across the cell plasma membrane. An ATP-fuelled Ca-pump, originally discovered and still best characterized in human red cells, is now believed to mediate resting Ca2+ extrusion in most animal cells. However, even in red cells, the truly physiological pump-leak turnover rate and cytoplasmic free Ca2+ level are unknown. Previous estimates were only very imprecise upper limits because normal intact red cells have a minute total pool of exchangeable Ca of less than 1 mumol 1 cells; Ca fluxes could not be measured without artificially increasing that pool with ionophores or disrupting the membrane to incorporate Ca buffers. Both procedures leave the membrane considerably leakier than in intact cells. Here, we have increased the exchangeable Ca pool by non-disruptively loading a Ca-chelator into intact cells, using intracellular hydrolysis of a membrane-permeant ester. The trapped chelator made the free cytoplasmic calcium concentration, [Ca2+]i, an easily defined function of directly measurable total cell Ca. We were then able to establish the physiological steady-state [Ca2+]i and pump-leak turnover rate of fresh cells suspended in their own plasma. If [Ca2+]i was lowered below the normal resting level, the Ca pump rate decreased according to the square of [Ca2+]i, and the inward Ca leak increased. The increase in leak did not develop if the cells were depleted of ATP and ADP. 相似文献
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Muzny DM Scherer SE Kaul R Wang J Yu J Sudbrak R Buhay CJ Chen R Cree A Ding Y Dugan-Rocha S Gill R Gunaratne P Harris RA Hawes AC Hernandez J Hodgson AV Hume J Jackson A Khan ZM Kovar-Smith C Lewis LR Lozado RJ Metzker ML Milosavljevic A Miner GR Morgan MB Nazareth LV Scott G Sodergren E Song XZ Steffen D Wei S Wheeler DA Wright MW Worley KC Yuan Y Zhang Z Adams CQ Ansari-Lari MA Ayele M Brown MJ Chen G Chen Z Clendenning J Clerc-Blankenburg KP Chen R Chen Z Davis C Delgado O Dinh HH Dong W 《Nature》2006,440(7088):1194-1198
After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion. 相似文献
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McClelland M Sanderson KE Clifton SW Latreille P Porwollik S Sabo A Meyer R Bieri T Ozersky P McLellan M Harkins CR Wang C Nguyen C Berghoff A Elliott G Kohlberg S Strong C Du F Carter J Kremizki C Layman D Leonard S Sun H Fulton L Nash W Miner T Minx P Delehaunty K Fronick C Magrini V Nhan M Warren W Florea L Spieth J Wilson RK 《Nature genetics》2004,36(12):1268-1274
Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae). 相似文献
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Gibbs RA Weinstock GM Metzker ML Muzny DM Sodergren EJ Scherer S Scott G Steffen D Worley KC Burch PE Okwuonu G Hines S Lewis L DeRamo C Delgado O Dugan-Rocha S Miner G Morgan M Hawes A Gill R Celera Holt RA Adams MD Amanatides PG Baden-Tillson H Barnstead M Chin S Evans CA Ferriera S Fosler C Glodek A Gu Z Jennings D Kraft CL Nguyen T Pfannkoch CM Sitter C Sutton GG Venter JC Woodage T Smith D Lee HM Gustafson E Cahill P Kana A Doucette-Stamm L Weinstock K Fechtel K Weiss RB Dunn DM Green ED 《Nature》2004,428(6982):493-521
The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution. 相似文献
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Hillier LW Fulton RS Fulton LA Graves TA Pepin KH Wagner-McPherson C Layman D Maas J Jaeger S Walker R Wylie K Sekhon M Becker MC O'Laughlin MD Schaller ME Fewell GA Delehaunty KD Miner TL Nash WE Cordes M Du H Sun H Edwards J Bradshaw-Cordum H Ali J Andrews S Isak A Vanbrunt A Nguyen C Du F Lamar B Courtney L Kalicki J Ozersky P Bielicki L Scott K Holmes A Harkins R Harris A Strong CM Hou S Tomlinson C Dauphin-Kohlberg S Kozlowicz-Reilly A Leonard S Rohlfing T Rock SM Tin-Wollam AM Abbott A 《Nature》2003,424(6945):157-164
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The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes 总被引:2,自引:0,他引:2
Skaletsky H Kuroda-Kawaguchi T Minx PJ Cordum HS Hillier L Brown LG Repping S Pyntikova T Ali J Bieri T Chinwalla A Delehaunty A Delehaunty K Du H Fewell G Fulton L Fulton R Graves T Hou SF Latrielle P Leonard S Mardis E Maupin R McPherson J Miner T Nash W Nguyen C Ozersky P Pepin K Rock S Rohlfing T Scott K Schultz B Strong C Tin-Wollam A Yang SP Waterston RH Wilson RK Rozen S Page DC 《Nature》2003,423(6942):825-837
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Ley TJ Mardis ER Ding L Fulton B McLellan MD Chen K Dooling D Dunford-Shore BH McGrath S Hickenbotham M Cook L Abbott R Larson DE Koboldt DC Pohl C Smith S Hawkins A Abbott S Locke D Hillier LW Miner T Fulton L Magrini V Wylie T Glasscock J Conyers J Sander N Shi X Osborne JR Minx P Gordon D Chinwalla A Zhao Y Ries RE Payton JE Westervelt P Tomasson MH Watson M Baty J Ivanovich J Heath S Shannon WD Nagarajan R Walter MJ Link DC Graubert TA DiPersio JF Wilson RK 《Nature》2008,456(7218):66-72
Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies. 相似文献