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Yalcin B Willis-Owen SA Fullerton J Meesaq A Deacon RM Rawlins JN Copley RR Morris AP Flint J Mott R 《Nature genetics》2004,36(11):1197-1202
Here we present a strategy to determine the genetic basis of variance in complex phenotypes that arise from natural, as opposed to induced, genetic variation in mice. We show that a commercially available strain of outbred mice, MF1, can be treated as an ultrafine mosaic of standard inbred strains and accordingly used to dissect a known quantitative trait locus influencing anxiety. We also show that this locus can be subdivided into three regions, one of which contains Rgs2, which encodes a regulator of G protein signaling. We then use quantitative complementation to show that Rgs2 is a quantitative trait gene. This combined genetic and functional approach should be applicable to the analysis of any quantitative trait. 相似文献
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Vinuesa CG Cook MC Angelucci C Athanasopoulos V Rui L Hill KM Yu D Domaschenz H Whittle B Lambe T Roberts IS Copley RR Bell JI Cornall RJ Goodnow CC 《Nature》2005,435(7041):452-458
Despite the sequencing of the human and mouse genomes, few genetic mechanisms for protecting against autoimmune disease are currently known. Here we systematically screen the mouse genome for autoimmune regulators to isolate a mouse strain, sanroque, with severe autoimmune disease resulting from a single recessive defect in a previously unknown mechanism for repressing antibody responses to self. The sanroque mutation acts within mature T cells to cause formation of excessive numbers of follicular helper T cells and germinal centres. The mutation disrupts a repressor of ICOS, an essential co-stimulatory receptor for follicular T cells, and results in excessive production of the cytokine interleukin-21. sanroque mice fail to repress diabetes-causing T cells, and develop high titres of autoantibodies and a pattern of pathology consistent with lupus. The causative mutation is in a gene of previously unknown function, roquin (Rc3h1), which encodes a highly conserved member of the RING-type ubiquitin ligase protein family. The Roquin protein is distinguished by the presence of a CCCH zinc-finger found in RNA-binding proteins, and localization to cytosolic RNA granules implicated in regulating messenger RNA translation and stability. 相似文献
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Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III 总被引:22,自引:0,他引:22
Gönczy P Echeverri C Oegema K Coulson A Jones SJ Copley RR Duperon J Oegema J Brehm M Cassin E Hannak E Kirkham M Pichler S Flohrs K Goessen A Leidel S Alleaume AM Martin C Ozlü N Bork P Hyman AA 《Nature》2000,408(6810):331-336
Genome sequencing projects generate a wealth of information; however, the ultimate goal of such projects is to accelerate the identification of the biological function of genes. This creates a need for comprehensive studies to fill the gap between sequence and function. Here we report the results of a functional genomic screen to identify genes required for cell division in Caenorhabditis elegans. We inhibited the expression of approximately 96% of the approximately 2,300 predicted open reading frames on chromosome III using RNA-mediated interference (RNAi). By using an in vivo time-lapse differential interference contrast microscopy assay, we identified 133 genes (approximately 6%) necessary for distinct cellular processes in early embryos. Our results indicate that these genes represent most of the genes on chromosome III that are required for proper cell division in C. elegans embryos. The complete data set, including sample time-lapse recordings, has been deposited in an open access database. We found that approximately 47% of the genes associated with a differential interference contrast phenotype have clear orthologues in other eukaryotes, indicating that this screen provides putative gene functions for other species as well. 相似文献
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GC/MS法追踪摇头丸杂质体系 总被引:1,自引:0,他引:1
本文运用GS/MS的总离子流法,选择离子法,对南京地区常见的几种摇头丸进行全面分析,找出与合成途径相关的痕量杂质,根据杂质情况初步确定其合成途径. 相似文献
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吐哈盆地台南凹陷鲁克沁构造带中的北西走向断层受挤压强烈 ,封闭性好 ;而北东走向断层封闭性差 ,常成为油气运移的良好通道。由于本区断块圈闭的有效性差 ,故不具备大规模聚集稀油的条件 ,但对稠变到一定程度的稠油能起较好的封堵作用。鲁克沁构造带高粘重质油的形成是原油运移和成藏阶段双重稠变作用的结果 ,并且油气的聚集是一个动态的过程。随着原油的逐渐稠变 ,所需要的封堵条件逐渐降低 ,油气的聚集过程才趋于稳定。鲁克沁构造带构造后期变革主要表现在构造幅度的增大 ,而未发生强烈的断裂作用 ,因此 ,前侏罗系油藏得以完好地保存 相似文献