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91.
Raychaudhuri S Remmers EF Lee AT Hackett R Guiducci C Burtt NP Gianniny L Korman BD Padyukov L Kurreeman FA Chang M Catanese JJ Ding B Wong S van der Helm-van Mil AH Neale BM Coblyn J Cui J Tak PP Wolbink GJ Crusius JB van der Horst-Bruinsma IE Criswell LA Amos CI Seldin MF Kastner DL Ardlie KG Alfredsson L Costenbader KH Altshuler D Huizinga TW Shadick NA Weinblatt ME de Vries N Worthington J Seielstad M Toes RE Karlson EW Begovich AB Klareskog L Gregersen PK Daly MJ Plenge RM 《Nature genetics》2008,40(10):1216-1223
To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls. We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall). 相似文献
92.
The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus) 总被引:1,自引:0,他引:1
Ming R Hou S Feng Y Yu Q Dionne-Laporte A Saw JH Senin P Wang W Ly BV Lewis KL Salzberg SL Feng L Jones MR Skelton RL Murray JE Chen C Qian W Shen J Du P Eustice M Tong E Tang H Lyons E Paull RE Michael TP Wall K Rice DW Albert H Wang ML Zhu YJ Schatz M Nagarajan N Acob RA Guan P Blas A Wai CM Ackerman CM Ren Y Liu C Wang J Wang J Na JK Shakirov EV Haas B Thimmapuram J Nelson D Wang X Bowers JE Gschwend AR Delcher AL Singh R Suzuki JY Tripathi S Neupane K Wei H Irikura B Paidi M Jiang N Zhang W 《Nature》2008,452(7190):991-996
Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of 'SunUp' papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties. 相似文献
93.
Jaillon O Bouhouche K Gout JF Aury JM Noel B Saudemont B Nowacki M Serrano V Porcel BM Ségurens B Le Mouël A Lepère G Schächter V Bétermier M Cohen J Wincker P Sperling L Duret L Meyer E 《Nature》2008,451(7176):359-362
Most eukaryotic genes are interrupted by non-coding introns that must be accurately removed from pre-messenger RNAs to produce translatable mRNAs. Splicing is guided locally by short conserved sequences, but genes typically contain many potential splice sites, and the mechanisms specifying the correct sites remain poorly understood. In most organisms, short introns recognized by the intron definition mechanism cannot be efficiently predicted solely on the basis of sequence motifs. In multicellular eukaryotes, long introns are recognized through exon definition and most genes produce multiple mRNA variants through alternative splicing. The nonsense-mediated mRNA decay (NMD) pathway may further shape the observed sets of variants by selectively degrading those containing premature termination codons, which are frequently produced in mammals. Here we show that the tiny introns of the ciliate Paramecium tetraurelia are under strong selective pressure to cause premature termination of mRNA translation in the event of intron retention, and that the same bias is observed among the short introns of plants, fungi and animals. By knocking down the two P. tetraurelia genes encoding UPF1, a protein that is crucial in NMD, we show that the intrinsic efficiency of splicing varies widely among introns and that NMD activity can significantly reduce the fraction of unspliced mRNAs. The results suggest that, independently of alternative splicing, species with large intron numbers universally rely on NMD to compensate for suboptimal splicing efficiency and accuracy. 相似文献
94.
The subduction of oceanic plateaux, which contain extraordinarily thick basaltic crust and are the marine counterparts of continental flood-basalt provinces, is an important factor in many current models of plate motion and provides a potential mechanism for triggering plate reorganization. To evaluate such models, it is essential to decipher the history of the collision between the largest and thickest of the world's oceanic plateaux, the Ontong Java plateau, and the Australian plate, but this has been hindered by poor constraints for the arrival of the plateau at the Melanesian trench. Here we present (40)Ar-(39)Ar geochronological data on hotspot volcanoes in eastern Australian that reveal a strong link between collision of the Greenland-sized Ontong Java plateau with the Melanesian arc and motion of the Australian plate. The new ages define a short-lived period of reduced northward plate motion between 26 and 23 Myr ago, coincident with an eastward offset in the contemporaneous tracks of seamount chains in the Tasman Sea east of Australia. These features record a brief westward deflection of the Australian plate as the plateau entered and choked the Melanesian trench 26 Myr ago. From 23 Myr ago, Australia returned to a rapid northerly trajectory at roughly the same time that southwest-directed subduction began along the Trobriand trough. The timing and brevity of this collisional event correlate well with offsets in hotspot seamount tracks on the Pacific plate, including the archetypal Hawaiian chain, and thus provide strong evidence that immense oceanic plateaux, like the Ontong Java, can contribute to initiating rapid change in plate boundaries and motions on a global scale. 相似文献
95.
The queen of a honeybee colony has a reproductive monopoly because her workers' ovaries are normally inactive and any eggs that they do lay are eaten by their fellow workers. But if a colony becomes queenless, the workers start to lay eggs, stop policing and rear a last batch of males before the colony finally dies out. Here we show that workers of the Asian dwarf red honeybee Apis florea from other colonies exploit this interval as an opportunity to move in and lay their own eggs while no policing is in force. Such parasitism of queenless colonies does not occur in the western honeybee A. mellifera and may be facilitated by the accessibility of A. florea nests, which are built out in the open. 相似文献
96.
Van Steen K McQueen MB Herbert A Raby B Lyon H Demeo DL Murphy A Su J Datta S Rosenow C Christman M Silverman EK Laird NM Weiss ST Lange C 《Nature genetics》2005,37(7):683-691
The Human Genome Project and its spin-offs are making it increasingly feasible to determine the genetic basis of complex traits using genome-wide association studies. The statistical challenge of analyzing such studies stems from the severe multiple-comparison problem resulting from the analysis of thousands of SNPs. Our methodology for genome-wide family-based association studies, using single SNPs or haplotypes, can identify associations that achieve genome-wide significance. In relation to developing guidelines for our screening tools, we determined lower bounds for the estimated power to detect the gene underlying the disease-susceptibility locus, which hold regardless of the linkage disequilibrium structure present in the data. We also assessed the power of our approach in the presence of multiple disease-susceptibility loci. Our screening tools accommodate genomic control and use the concept of haplotype-tagging SNPs. Our methods use the entire sample and do not require separate screening and validation samples to establish genome-wide significance, as population-based designs do. 相似文献
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99.
Klironomos JN Allen MF Rillig MC Piotrowski J Makvandi-Nejad S Wolfe BE Powell JR 《Nature》2005,433(7026):621-624
Attempts to understand the ecological effect of increasing atmospheric CO2 concentration, [CO2], usually involve exposing today's ecosystems to expected future [CO2] levels. However, a major assumption of these approaches has not been tested--that exposing ecosystems to a single-step increase in [CO2] will yield similar responses to those of a gradual increase over several decades. We tested this assumption on a mycorrhizal fungal community over a period of six years. [CO2] was either increased abruptly, as is typical of most [CO2] experiments, or more gradually over 21 generations. The two approaches resulted in different structural and functional community responses to increased [CO2]. Some fungi were sensitive to the carbon pulse of the abrupt [CO2] treatment. This resulted in an immediate decline in fungal species richness and a significant change in mycorrhizal functioning. The magnitude of changes in fungal diversity and functioning in response to gradually increasing [CO2] was smaller, and not significantly different to those with ambient [CO2]. Our results suggest that studies may overestimate some community responses to increasing [CO2] because biota may be sensitive to ecosystem changes that occur as a result of abrupt increases. 相似文献
100.