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91.
Genomic control for association studies 总被引:96,自引:0,他引:96
A dense set of single nucleotide polymorphisms (SNP) covering the genome and an efficient method to assess SNP genotypes are expected to be available in the near future. An outstanding question is how to use these technologies efficiently to identify genes affecting liability to complex disorders. To achieve this goal, we propose a statistical method that has several optimal properties: It can be used with case control data and yet, like family-based designs, controls for population heterogeneity; it is insensitive to the usual violations of model assumptions, such as cases failing to be strictly independent; and, by using Bayesian outlier methods, it circumvents the need for Bonferroni correction for multiple tests, leading to better performance in many settings while still constraining risk for false positives. The performance of our genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders. 相似文献
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93.
目的 通过开展周六手术,缩短病人平均术前等待日及平均住院日。在保证医疗质量的前提下,达到提高效率,增加产能的目的。方法 在多部门协作的基础上,开展周六手术,改变原有人力配置方式和手术流程,以配合周六手术的进行。结果 手术流程再造后,与之前同期相比术前等待日缩短25.00%, 月平均手术台次增加12.35%, 病人平均住院日降低9.22%。结论 开展周六手术,能缩短患者平均住院日和术前等待日,为患者节约宝贵的时间和金钱,在一定程度上解决了患者看病难、看病贵的问题,提高了医院的工作效率。 相似文献
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95.
This article examines the development of the ‘cultural competition’ as a site for the production of multiple identities by Indian American youths on American college campuses. Through the examination of two categories of folk dance competitions (bhangra and raas-garba) at a private university in Washington, DC, we argue that these competitions appear to resist hybridity and produce rhetoric that marginalizes diasporic culture in favour of the ‘pure’ and ‘authentic’ culture of the homeland. However, the goal of expressing uncontaminated ‘authentic’ culture is not realized as diasporic identities and cultures consistently interrupt and undermine homogenizing narratives of ‘tradition’ and ‘authenticity’. We also demonstrate that these folk dance groups often reinforce an ethno-regional distinctiveness rather than a hybrid or pan-Indian identity. 相似文献
96.
ATP-binding cassette (ABC) transporters serve as importers and exporters for a wide variety of solutes in both prokaryotes
and eukaryotes, and are implicated in microbial drug resistance and a number of significant human genetic disorders. Initial
crystal structures of the soluble nucleotide binding domains (NBDs) of ABC transporters, while a significant step towards
understanding the coupling of ATP binding and hydrolysis to transport, presented researchers with important questions surrounding
the role of the signature sequence residues, the composition of the nucleotide binding sites, and the mode of NBD dimerization
during the transport reaction cycle. Recent studies have begun to address these concerns. This mini-review summarizes the
biochemical and structural characterizations of two archaebacterial NBDs from Methanocaldococcus jannaschii, MJ0796 and MJ1267, and offers current perspectives on the functional mechanism of ABC transporters. 相似文献
97.
本研究检测了在冬虫夏草成熟过程中突变基因型冬虫夏草菌在子座中表达的动态变化。根据冬虫夏草菌基因内转录间隔区(ITS)序列中大量散在的点突变,设计了8个单核苷酸多态性(SNP)延伸引物,采用SNP质谱基因分型法测定各个SNP位点的单核苷酸延伸反应,观察冬虫夏草子座中转换突变和颠换突变基因型菌在冬虫夏草成熟过程中表达的动态变化。其中5个SNP延伸引物(067721-211,067721-240,067721-477,067721-531和067721-581)位于rDNA ITS1和ITS2段,用于区分GC和AT偏倚基因型,但不区分2个AT偏倚基因型。另外3个延伸引物(067740-324,067740-328和067740-360)位于rDNA 5.8S段,用于区分2个AT基因型。采用PCR+EcoRⅠ限制性酶切法检验2个GC偏倚基因型冬虫夏草菌在冬虫夏草成熟过程中表达的动态变化。结果表明:冬虫夏草子座rDNA ITS1-5.8S-ITS2片段的8个SNP位点的质谱图谱显示冬虫夏草子座中存在至少5个冬虫夏草菌转换突变和颠换突变等位基因。它们的表达在冬虫夏草成熟过程中呈现动态变化。067721-211和067721-477位点的AT偏倚型等位基因的峰高明显高于GC偏倚型;随着冬虫夏草的成熟,这2个位点的AT型等位基因峰高大幅度下降。SNP质谱图不仅显示转换突变的等位基因,颠换突变等位基因也有很高的检出率,它们的峰高在一些位点甚至超过GC和AT基因型等位基因;随着冬虫夏草的成熟,颠换突变等位基因的检出率和峰高趋于下降。在区分2个AT偏倚基因型的研究中,AB067744和AB067740 2个基因型的等位基因同时存在于未成熟冬虫夏草子座中。随着冬虫夏草的成熟,AB067744基因型等位基因的峰高明显降低,而AB067740基因型等位基因的峰高明显升高。PCR产物EcoRⅠ酶切试验发现子座中存在2组GC偏倚型菌,具有完全不同的成熟模式。综上,冬虫夏草子座中存在至少6个突变基因型冬虫夏草菌,其表达随着冬虫夏草的成熟呈现动态变化。这些突变基因型菌表达的动态变化对于冬虫夏草子座的萌发和成熟具有重要菌物学意义。 相似文献
98.
99.
Ken Hirano Yuichiro Yoshida Tomomi Ishido Naoji Moriya Yoshiyuki Mizushina Mitsuru Ishikawa 《Analytical biochemistry》2010,405(2):160-199
In the present study, we investigated mammalian polymerases that consecutively incorporate various fluorophore-labeled nucleotides. We found that rat DNA polymerase β (pol β) consecutively incorporated fluorophore-labeled nucleotides to a greater extent than four bacterial polymerases, Sequenase Version 2.0, VentR (exo-), DNA polymerase IIIα and the Klenow fragment, and the mammalian polymerases DNA polymerase α and human DNA polymerase δ, under mesophilic conditions. Furthermore, we investigated the kinetics of correct or mismatched incorporation with labeled nucleotides during synthesis by rat pol β. The kinetic parameters Km and kcat were measured and used for evaluating: (i) the discrimination against correct pair incorporation of labeled nucleotides relative to unlabeled nucleotides; and (ii) the fidelity for all nucleotide combinations of mismatched pairs in the presence of labeled or unlabeled nucleotides. We also investigated the effect of fluorophore-labeled nucleotides on terminal deoxynucleotidyl transferase activity of rat pol β. We have demonstrated for the first time that mammalian pol β can consecutively incorporate various fluorophore-labeled dNTPs. These findings suggest that pol β is useful for high-density labeling of DNA probes and single-molecule sequencing for high-speed genome analysis. 相似文献
100.