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排序方式: 共有261条查询结果,搜索用时 31 毫秒
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Hunt KA Smyth DJ Balschun T Ban M Mistry V Ahmad T Anand V Barrett JC Bhaw-Rosun L Bockett NA Brand OJ Brouwer E Concannon P Cooper JD Dias KR van Diemen CC Dubois PC Edkins S Fölster-Holst R Fransen K Glass DN Heap GA Hofmann S Huizinga TW Hunt S Langford C Lee J Mansfield J Marrosu MG Mathew CG Mein CA Müller-Quernheim J Nutland S Onengut-Gumuscu S Ouwehand W Pearce K Prescott NJ Posthumus MD Potter S Rosati G Sambrook J Satsangi J Schreiber S Shtir C Simmonds MJ Sudman M Thompson SD Toes R 《Nature genetics》2012,44(1):3-5
73.
Comas I Borrell S Roetzer A Rose G Malla B Kato-Maeda M Galagan J Niemann S Gagneux S 《Nature genetics》2012,44(1):106-110
Epidemics of drug-resistant bacteria emerge worldwide, even as resistant strains frequently have reduced fitness compared to their drug-susceptible counterparts. Data from model systems suggest that the fitness cost of antimicrobial resistance can be reduced by compensatory mutations; however, there is limited evidence that compensatory evolution has any significant role in the success of drug-resistant bacteria in human populations. Here we describe a set of compensatory mutations in the RNA polymerase genes of rifampicin-resistant M. tuberculosis, the etiologic agent of human tuberculosis (TB). M. tuberculosis strains harboring these compensatory mutations showed a high competitive fitness in vitro. Moreover, these mutations were associated with high fitness in vivo, as determined by examining their relative clinical frequency across patient populations. Of note, in countries with the world's highest incidence of multidrug-resistant (MDR) TB, more than 30% of MDR clinical isolates had this form of mutation. Our findings support a role for compensatory evolution in the global epidemics of MDR TB. 相似文献
74.
Brown KM Macgregor S Montgomery GW Craig DW Zhao ZZ Iyadurai K Henders AK Homer N Campbell MJ Stark M Thomas S Schmid H Holland EA Gillanders EM Duffy DL Maskiell JA Jetann J Ferguson M Stephan DA Cust AE Whiteman D Green A Olsson H Puig S Ghiorzo P Hansson J Demenais F Goldstein AM Gruis NA Elder DE Bishop JN Kefford RF Giles GG Armstrong BK Aitken JF Hopper JL Martin NG Trent JM Mann GJ Hayward NK 《Nature genetics》2008,40(7):838-840
We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases. 相似文献
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Ross MT Grafham DV Coffey AJ Scherer S McLay K Muzny D Platzer M Howell GR Burrows C Bird CP Frankish A Lovell FL Howe KL Ashurst JL Fulton RS Sudbrak R Wen G Jones MC Hurles ME Andrews TD Scott CE Searle S Ramser J Whittaker A Deadman R Carter NP Hunt SE Chen R Cree A Gunaratne P Havlak P Hodgson A Metzker ML Richards S Scott G Steffen D Sodergren E Wheeler DA Worley KC Ainscough R Ambrose KD Ansari-Lari MA Aradhya S Ashwell RI Babbage AK Bagguley CL Ballabio A Banerjee R Barker GE Barlow KF 《Nature》2005,434(7031):325-337
The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. 相似文献
77.
Biomarker evidence for green and purple sulphur bacteria in a stratified Palaeoproterozoic sea 总被引:2,自引:0,他引:2
The disappearance of iron formations from the geological record approximately 1.8 billion years (Gyr) ago was the consequence of rising oxygen levels in the atmosphere starting 2.45-2.32 Gyr ago. It marks the end of a 2.5-Gyr period dominated by anoxic and iron-rich deep oceans. However, despite rising oxygen levels and a concomitant increase in marine sulphate concentration, related to enhanced sulphide oxidation during continental weathering, the chemistry of the oceans in the following mid-Proterozoic interval (approximately 1.8-0.8 Gyr ago) probably did not yet resemble our oxygen-rich modern oceans. Recent data indicate that marine oxygen and sulphate concentrations may have remained well below current levels during this period, with one model indicating that anoxic and sulphidic marine basins were widespread, and perhaps even globally distributed. Here we present hydrocarbon biomarkers (molecular fossils) from a 1.64-Gyr-old basin in northern Australia, revealing the ecological structure of mid-Proterozoic marine communities. The biomarkers signify a marine basin with anoxic, sulphidic, sulphate-poor and permanently stratified deep waters, hostile to eukaryotic algae. Phototrophic purple sulphur bacteria (Chromatiaceae) were detected in the geological record based on the new carotenoid biomarker okenane, and they seem to have co-existed with communities of green sulphur bacteria (Chlorobiaceae). Collectively, the biomarkers support mounting evidence for a long-lasting Proterozoic world in which oxygen levels remained well below modern levels. 相似文献
78.
Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes 总被引:3,自引:0,他引:3
Yang Q Graham TE Mody N Preitner F Peroni OD Zabolotny JM Kotani K Quadro L Kahn BB 《Nature》2005,436(7049):356-362
In obesity and type 2 diabetes, expression of the GLUT4 glucose transporter is decreased selectively in adipocytes. Adipose-specific Glut4 (also known as Slc2a4) knockout (adipose-Glut4(-/-)) mice show insulin resistance secondarily in muscle and liver. Here we show, using DNA arrays, that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4(-/-) mice. We show that serum RBP4 levels are elevated in insulin-resistant mice and humans with obesity and type 2 diabetes. RBP4 levels are normalized by rosiglitazone, an insulin-sensitizing drug. Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of Rbp4 enhances insulin sensitivity. Fenretinide, a synthetic retinoid that increases urinary excretion of RBP4, normalizes serum RBP4 levels and improves insulin resistance and glucose intolerance in mice with obesity induced by a high-fat diet. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and impairs insulin signalling in muscle. Thus, RBP4 is an adipocyte-derived 'signal' that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes. 相似文献
79.
An evaluation of HapMap sample size and tagging SNP performance in large-scale empirical and simulated data sets 总被引:7,自引:0,他引:7
Zeggini E Rayner W Morris AP Hattersley AT Walker M Hitman GA Deloukas P Cardon LR McCarthy MI 《Nature genetics》2005,37(12):1320-1322
A substantial investment has been made in the generation of large public resources designed to enable the identification of tag SNP sets, but data establishing the adequacy of the sample sizes used are limited. Using large-scale empirical and simulated data sets, we found that the sample sizes used in the HapMap project are sufficient to capture common variation, but that performance declines substantially for variants with minor allele frequencies of <5%. 相似文献
80.