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961.
Hundreds of variants clustered in genomic loci and biological pathways affect human height 总被引:2,自引:0,他引:2
Lango Allen H Estrada K Lettre G Berndt SI Weedon MN Rivadeneira F Willer CJ Jackson AU Vedantam S Raychaudhuri S Ferreira T Wood AR Weyant RJ Segrè AV Speliotes EK Wheeler E Soranzo N Park JH Yang J Gudbjartsson D Heard-Costa NL Randall JC Qi L Vernon Smith A Mägi R Pastinen T Liang L Heid IM Luan J Thorleifsson G Winkler TW Goddard ME Sin Lo K Palmer C Workalemahu T Aulchenko YS Johansson A Zillikens MC Feitosa MF Esko T Johnson T Ketkar S Kraft P Mangino M Prokopenko I Absher D Albrecht E 《Nature》2010,467(7317):832-838
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P?0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways. 相似文献
962.
为实现236U的高灵敏测量,对意大利那不勒斯第二大学的同位素研究环境与文化遗产中心的加速器质谱装置进行了升级改造。采用单缝单丝法测量了238U的束流发射度,并与13C和H的束流发射度进行了比较。测量结果表明,238U在X方向和Y方向的边界发射度分别为(9.5±1.0)、(2.7±0.3)mm.m rad。根据测量的发射度数值,确定了拟安装的飞行时间探测器在束流线上的位置。 相似文献
963.
分析了燃油乳化液射流的发展模型和游离水的微爆炸特性,提出空化对射流的破坏作用能使射流雾化角发生改变,因此判定乳化燃油雾化效果的一个重要准则是雾化角。在给定容积的容器内充入氮气,采用遮盖式喷嘴,利用高速摄影机分析了无水柴油和具有不同含水量的柴油乳化液射流在高压脉冲喷射气体介质时游离水滴发生微爆炸的喷雾特性。理论和实验研究表明:燃油中含有大量的微小水滴降低了卸载时射流断裂的动力强度,使其具有更强的分散性。柴油乳化液比无水柴油能喷射出更多的体积,射流宽度变大,喷射的雾化角增大,当乳化液中水的含量为10%时,喷射雾化角达到最大值。 相似文献
964.
通过对吉林省长春、 德惠、 扶余、 公主岭和永吉区域内典型农田土壤进行网格法布点采样, 分析土壤中有机氯农药的残留及在农田土壤中的分布状况, 并探讨有机氯农药残留物的组成及其分布和来源. 结果表明: 研究区域内六六六类(HCHs)和滴滴涕类(DDTs)农药残留检出率较高, 总有机氯农药(OCPs)的残留范围为1.45~83.88 ng/g, HCHs的总质量比为1.17~27.83 ng/g, DDTs农药的总质量比为1.45~81.75 ng/g; OCPs总体分布为长春>公主岭>永吉>德惠>扶余. OCPs的总量与总有机碳(TOC)呈显著的正相关关系; 长春、 德惠、 公主岭和永吉土壤中α-HCH/γ-HCH的平均值为0.37, 即大部分采样点可能有大量林丹(γ-HCH)输入; 除公主岭外, 各采样点的P,P′ DDT/(P,P′-DDD+P,P′-DDE)平均值都小于1, 即土壤中的DDTs类物质主要来自历史残留物, 公主岭部分点位可能受到工业DDTs的影响; 长春区域污染明显高于其他区域; 六六六类以γ-HCH为主要污染物, 滴滴涕类以P,P′-DDT为主要污染物. 相似文献
965.
为了探讨S8联合小分子化合物Z18的抗肿瘤效应,本研究通过联合用药方式处理HeLa细胞后,采用台盼蓝染色和流式细胞仪对细胞死亡率和死亡方式进行检测。电镜实验证实Z18诱导细胞自噬,并利用Western Blotting检测联合用药后LC3-II的变化和使用转染了GFP-LC3或mRFP-EGFP-LC3的HeLa细胞检测联合用药对细胞自噬和自噬流的影响。最后通过ATG5 siRNA和CQ抑制自噬和自噬流,观察联合用药对细胞的自噬和死亡的变化,进一步研究S8对Z18的抗肿瘤作用的影响。结果显示,S8联合用药后,细胞死亡率显著升高(P<0.05),死亡方式主要以坏死为主。S8明显地促进了Z18对HeLa细胞的毒性,其促进作用具有剂量依赖性。但联合用药并未降低Z18引起的自噬空泡集聚,LC3-II蛋白表达也未发生变化。抑制自噬后,并未影响联合用药促进细胞死亡的结果。因此,Z18在联合使用S8的情况下,细胞自噬水平没有发生明显变化,而细胞死亡比例明显升高,自噬并不影响联合用药诱导的细胞死亡。S8可能通过调节细胞坏死的其他途径进而促进细胞对Z18的敏感性,并进一步使细胞发生坏死。 相似文献
966.
基于SIP的多媒体业务穿越网络地址转换/防火墙研究与设计 总被引:1,自引:0,他引:1
研究了IETF关于NGN网络中会话业务穿透NAT技术的各种草案,结合网络的实际情况,对目前SIP业务开展可以使用的几种NAT穿越技术和方案进行了比较,提出了一种结合SIP协议扩展和MIDCOM协议构架的方法,解决了由于传统NAT/FW设备不支持SIP协议,而造成的私网内SIP终端同Internet上的SIP终端之间业务无法互通问题.通过用SIP信令建立的语音会话仿真表明,该方法具有可行性和有效性. 相似文献
967.
对于高频雷达系统,通常很难找到一段连续可用的“寂静”频带,为了获得大的距离分辨带宽,可以离散地利用多段可用频带。然而,信号频谱的离散性会造成较高的距离旁瓣。所研究的全随机跳频脉冲信号,通过控制不同频率脉冲出现的概率可以获得较低的距离旁瓣。研究了全随机跳频脉冲信号自相关函数的统计特性,并给出了可用频带连续及非连续两种情况下的信号设计方法。 相似文献
968.
Korevaar PA George SJ Markvoort AJ Smulders MM Hilbers PA Schenning AP De Greef TF Meijer EW 《Nature》2012,481(7382):492-496
Self-assembly provides an attractive route to functional organic materials, with properties and hence performance depending sensitively on the organization of the molecular building blocks. Molecular organization is a direct consequence of the pathways involved in the supramolecular assembly process, which is more amenable to detailed study when using one-dimensional systems. In the case of protein fibrils, formation and growth have been attributed to complex aggregation pathways that go beyond traditional concepts of homogeneous and secondary nucleation events. The self-assembly of synthetic supramolecular polymers has also been studied and even modulated, but our quantitative understanding of the processes involved remains limited. Here we report time-resolved observations of the formation of supramolecular polymers from π-conjugated oligomers. Our kinetic experiments show the presence of a kinetically favoured metastable assembly that forms quickly but then transforms into the thermodynamically favoured form. Quantitative insight into the kinetic experiments was obtained from kinetic model calculations, which revealed two parallel and competing pathways leading to assemblies with opposite helicity. These insights prompt us to use a chiral tartaric acid as an auxiliary to change the thermodynamic preference of the assembly process. We find that we can force aggregation completely down the kinetically favoured pathway so that, on removal of the auxiliary, we obtain only metastable assemblies. 相似文献
969.
970.
Beck PG Montalban J Kallinger T De Ridder J Aerts C García RA Hekker S Dupret MA Mosser B Eggenberger P Stello D Elsworth Y Frandsen S Carrier F Hillen M Gruberbauer M Christensen-Dalsgaard J Miglio A Valentini M Bedding TR Kjeldsen H Girouard FR Hall JR Ibrahim KA 《Nature》2012,481(7379):55-57
When the core hydrogen is exhausted during stellar evolution, the central region of a star contracts and the outer envelope expands and cools, giving rise to a red giant. Convection takes place over much of the star's radius. Conservation of angular momentum requires that the cores of these stars rotate faster than their envelopes; indirect evidence supports this. Information about the angular-momentum distribution is inaccessible to direct observations, but it can be extracted from the effect of rotation on oscillation modes that probe the stellar interior. Here we report an increasing rotation rate from the surface of the star to the stellar core in the interiors of red giants, obtained using the rotational frequency splitting of recently detected 'mixed modes'. By comparison with theoretical stellar models, we conclude that the core must rotate at least ten times faster than the surface. This observational result confirms the theoretical prediction of a steep gradient in the rotation profile towards the deep stellar interior. 相似文献