排序方式: 共有102条查询结果,搜索用时 203 毫秒
41.
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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The article addresses the topic of the growth of mathematical knowledge with a special focus on the question: How are mathematical objects introduced to mathematical practice? It takes as starting point a proposal made in a previous paper which is based on a case study on the introduction of Riemann surfaces. The claim is that (i) a new object first refers to previously accepted objects, and that (ii) reasoning is possible via a correspondence to the objects with reference to which it is introduced. In addition Riemann surfaces are geometrical objects, i.e., they are placed in a geometrical context, which makes new definitions possible. This proposal is tested on a case study on Minkowski’s introduction of convex bodies. The conclusion is that the proposal holds also for this example. In both cases we notice that in a first stage is a close connection between the new object and the objects it is introduced with reference to, and that in a later stage, the new object is given an independent definition. Even though the two cases display similarity in these respects, we also point to certain differences between the cases in the process of the first stage. Overall we notice the fruitfulness of representing problems in different contexts. 相似文献
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Morin RD Mendez-Lago M Mungall AJ Goya R Mungall KL Corbett RD Johnson NA Severson TM Chiu R Field M Jackman S Krzywinski M Scott DW Trinh DL Tamura-Wells J Li S Firme MR Rogic S Griffith M Chan S Yakovenko O Meyer IM Zhao EY Smailus D Moksa M Chittaranjan S Rimsza L Brooks-Wilson A Spinelli JJ Ben-Neriah S Meissner B Woolcock B Boyle M McDonald H Tam A Zhao Y Delaney A Zeng T Tse K Butterfield Y Birol I Holt R Schein J Horsman DE Moore R Jones SJ Connors JM Hirst M Gascoyne RD Marra MA 《Nature》2011,476(7360):298-303
Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis. 相似文献
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Alföldi J Di Palma F Grabherr M Williams C Kong L Mauceli E Russell P Lowe CB Glor RE Jaffe JD Ray DA Boissinot S Shedlock AM Botka C Castoe TA Colbourne JK Fujita MK Moreno RG ten Hallers BF Haussler D Heger A Heiman D Janes DE Johnson J de Jong PJ Koriabine MY Lara M Novick PA Organ CL Peach SE Poe S Pollock DD de Queiroz K Sanger T Searle S Smith JD Smith Z Swofford R Turner-Maier J Wade J Young S Zadissa A Edwards SV Glenn TC Schneider CJ Losos JB Lander ES Breen M Ponting CP Lindblad-Toh K 《Nature》2011,477(7366):587-591
The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations. 相似文献
45.
Jordan Sinclair John M. Emlen Matthew Rinella Jessica Snelgrove D. Carl Freeman 《西北部美国博物学家》2011,69(4)
Wind-pollinated dioecious plants often exhibit spatial segregation of the sexes. This partial niche separation has most often been explored using abiotic niche axes. However, if the sexes are truly separated in space, then they are apt to encounter different plant species that may heavily affect growth and reproduction. Also, to the extent that their niches differ, the sexes may respond differently to the same co-occurring species. Here we examine interspecific interactions that influence male and female reproductive potential in Atriplex bonnevillensis. Using Emlen’s interaction assessment, a technique which assesses species interactions based on cover classes, we show that Salsola species compete significantly with females but not males, while Halogeton glomeratus competes with males but not females. The effect of competition only became apparent when we corrected for site-specific fertility. These results imply that differential competition must be considered when studying dioecious plants that display spatial segregation of the sexes. 相似文献
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Drosophila show innate olfactory-driven behaviours that are observed in naive animals without previous learning or experience, suggesting that the neural circuits that mediate these behaviours are genetically programmed. Despite the numerical simplicity of the fly nervous system, features of the anatomical organization of the fly brain often confound the delineation of these circuits. Here we identify a neural circuit responsive to cVA, a pheromone that elicits sexually dimorphic behaviours. We have combined neural tracing using an improved photoactivatable green fluorescent protein (PA-GFP) with electrophysiology, optical imaging and laser-mediated microlesioning to map this circuit from the activation of sensory neurons in the antennae to the excitation of descending neurons in the ventral nerve cord. This circuit is concise and minimally comprises four neurons, connected by three synapses. Three of these neurons are overtly dimorphic and identify a male-specific neuropil that integrates inputs from multiple sensory systems and sends outputs to the ventral nerve cord. This neural pathway suggests a means by which a single pheromone can elicit different behaviours in the two sexes. 相似文献
48.
LS Andersson M Larhammar F Memic H Wootz D Schwochow CJ Rubin K Patra T Arnason L Wellbring G Hjälm F Imsland JL Petersen ME McCue JR Mickelson G Cothran N Ahituv L Roepstorff S Mikko A Vallstedt G Lindgren L Andersson K Kullander 《Nature》2012,488(7413):642-646
Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement. These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation. 相似文献
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Guan K Nayernia K Maier LS Wagner S Dressel R Lee JH Nolte J Wolf F Li M Engel W Hasenfuss G 《Nature》2006,440(7088):1199-1203
Embryonic germ cells as well as germline stem cells from neonatal mouse testis are pluripotent and have differentiation potential similar to embryonic stem cells, suggesting that the germline lineage may retain the ability to generate pluripotent cells. However, until now there has been no evidence for the pluripotency and plasticity of adult spermatogonial stem cells (SSCs), which are responsible for maintaining spermatogenesis throughout life in the male. Here we show the isolation of SSCs from adult mouse testis using genetic selection, with a success rate of 27%. These isolated SSCs respond to culture conditions and acquire embryonic stem cell properties. We name these cells multipotent adult germline stem cells (maGSCs). They are able to spontaneously differentiate into derivatives of the three embryonic germ layers in vitro and generate teratomas in immunodeficient mice. When injected into an early blastocyst, SSCs contribute to the development of various organs and show germline transmission. Thus, the capacity to form multipotent cells persists in adult mouse testis. Establishment of human maGSCs from testicular biopsies may allow individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells. Furthermore, these cells may provide new opportunities to study genetic diseases in various cell lineages. 相似文献