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971.
This article focuses on conducting global testing for association between a binary trait and a set of rare variants (RVs), although its application can be much broader to other types of traits, common variants (CVs), and gene set or pathway analysis. We show that many of the existing tests have deteriorating performance in the presence of many nonassociated RVs: their power can dramatically drop as the proportion of nonassociated RVs in the group to be tested increases. We propose a class of so-called sum of powered score (SPU) tests, each of which is based on the score vector from a general regression model and hence can deal with different types of traits and adjust for covariates, e.g., principal components accounting for population stratification. The SPU tests generalize the sum test, a representative burden test based on pooling or collapsing genotypes of RVs, and a sum of squared score (SSU) test that is closely related to several other powerful variance component tests; a previous study (Basu and Pan 2011) has demonstrated good performance of one, but not both, of the Sum and SSU tests in many situations. The SPU tests are versatile in the sense that one of them is often powerful, although its identity varies with the unknown true association parameters. We propose an adaptive SPU (aSPU) test to approximate the most powerful SPU test for a given scenario, consequently maintaining high power and being highly adaptive across various scenarios. We conducted extensive simulations to show superior performance of the aSPU test over several state-of-the-art association tests in the presence of many nonassociated RVs. Finally we applied the SPU and aSPU tests to the GAW17 mini-exome sequence data to compare its practical performance with some existing tests, demonstrating their potential usefulness. 相似文献
972.
Familial resemblance in the second‐to‐fourth digit ratio (2D:4D), a proxy for prenatal androgen action, was studied in 1,260 individuals from 235 Austrian families. In agreement with findings from twin studies of 2D:4D, heritability estimates based on parent–child and full‐sib dyad similarity indicated substantial genetic contributions to trait expression (57% for right hand, 48% for left hand 2D:4D). Because twin studies have found nonadditive genetic as well as shared environmental effects on 2D:4D to be negligible or nil, these family‐based estimates in all likelihood reflect the narrow‐sense (additive genetic) heritability of the trait. Directional (right‐minus‐left) asymmetry in 2D:4D was only weakly heritable (6%). The pattern of same‐sex and different‐sex parent–child and full‐sib correlations yielded no evidence for X‐linked inheritance. This is surprising, considering evidence for associations of male 2D:4D with sensitivity to testosterone (functional variants of the X‐linked androgen receptor gene). 2D:4D was particularly strongly heritable through male lines (father–son and brother–brother correlations), thus raising the possibility that Y‐linked genes (such as the sex‐determining region SRY) might influence 2D:4D expression. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
973.
IGF2 polymorphisms are associated with hepatitis B virus clearance and hepatocellular carcinoma 总被引:4,自引:0,他引:4
Kim YJ Yoon JH Kim CY Kim LH Park BL Shin HD Lee HS 《Biochemical and biophysical research communications》2006,346(1):38-44
The aim of this study was to determine whether IGF2 polymorphisms are associated with the clearance of hepatitis B virus (HBV) infection and the risk of hepatocellular carcinoma (HCC). A total of 1095 Korean subjects were prospectively enrolled in this case-control study. The rates of IGF2 polymorphisms were determined in each group. The IGF2+820G allele (IGF2+820G/G) and the IGF2+6815A/A genotype were strongly associated with the resolution of HBV infection (OR=0.62-0.73; P=0.001-0.03 and OR=0.71; P=0.03, respectively). Haplotype analysis showed that IGF2-haplotype5 (A-C-C-T-A-T-G) and IGF2-haplotype1 (T-C-T-T-A-C-A) were significantly associated with the clearance and persistence of HBV infection (OR=0.55-0.58, P=0.009-0.01 and OR=1.31-1.65, P=0.001-0.007, respectively). On the other hand, the IGF2+2482C/C or +820G/G genotypes were significantly associated with a higher risk of HCC (OR=1.88, 1.68; P=0.04). IGF2 polymorphisms were found to be strongly associated with the clearance of HBV or the occurrence of HCC in patients with chronic HBV infection. 相似文献
974.
Huys I Waelkens E Tytgat J 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,803(1):67-73
Chlorotoxin has been isolated from the venom of the scorpion Leiurus quinquestriatus and characterized as a 4.1kDa peptide, containing a lysine at position 27 that is also present in many Kv-blocking toxins. Because chlorotoxin shows no affinity for Kv-channels, we intended to design, express and purify a chlorotoxin-chimer, containing the active binding site (beta-sheet) of a very potent Kv1-channel blocking peptide, agitoxin 2, by mutating three original residues in the chlorotoxin molecule. Several derivatives of the chimer, gradually missing one additional amino acid residue at the N-terminal side of the peptide, were produced and identified chromatographically. In contrast to chlorotoxin, these chimer derivatives are capable of blocking cloned Kv1-channels. 相似文献
975.
日龄雏鸡的学习记忆模型及其分子机制和药理学研究进展 总被引:1,自引:0,他引:1
日龄雏鸡一次性被动回避学习和厌恶性条件化学习模型被广泛用于学习记忆机制的研究,并取得了很大的进展. 上纹体和旁嗅核是参与雏鸡学习记忆的主要脑区. 结合相关的分子机制研究,药理学实验发现了多种能影响不同记忆阶段的药物,如去甲肾上腺素对长时记忆有增强和调控作用. 由于鸟类和哺乳动物与记忆相关的脑结构和功能具有一定可比性,上述工作可为了解大脑的学习记忆功能提供重要参考. 相似文献
976.
A comparison of the phosphorylated and unphosphorylated forms of isocitrate dehydrogenase from Escherichia coli ML308 总被引:2,自引:0,他引:2
NADP+ can protect active isocitrate dehydrogenase against attack by several proteases. Inactive phosphorylated isocitrate dehydrogenase is much less susceptible to proteolysis than the active enzyme, and it is not protected by NADP+. The results suggest that binding of NADP+ to, or phosphorylation of, active isocitrate dehydrogenase induces similar conformational states. Fluorescence titration experiments show that NADPH can bind to active but not to inactive isocitrate dehydrogenase. It is suggested that the phosphorylation of isocitrate dehydrogenase may occur close to its coenzyme binding site. 相似文献
977.
从寄畅园的始建年代、历史沿革和重要议题3个方面,论述寄畅园作为个案研究的价值与意义。1)采用史源学、年代学和微观史学等方法,考证寄畅园始建于1527年。2)将寄畅园490年的历史分为9个时期,论述各时期的关键史实和风格特征。3)从家史与国史、造园与改园、南巡与写仿、茶曲与书画、保护与利用5个方面,分析寄畅园的重要议题。最后探讨了“寄畅园学”的开展方式。 相似文献
978.
C. Fernández 《欧洲藻类学杂志》2013,48(4):352-360
Recent changes in kelp distribution along the north coast of Spain are described and analysed through a long-term population study focused on Saccorhiza polyschides. The main purpose of this work was to understand which population processes are more sensitive to increased sea surface temperatures and reductions in the intensity of upwelling episodes in the current scenario of global warming. Data on the distribution of kelp species (old and recent data) were obtained from the literature and compared with current species distributions assessed by field sampling between 2007 and 2010 and covering a transition coastline of 200 km. The long-term population study of Saccorhiza polyschides was conducted at a site close to the edge of its current distribution. Data for recruitment, growth and survival, as well as density and supported biomass of populations collected since the 1990s were analysed using data from the late 1970s for comparison. Kelps on the north coast of Spain have shown a westward retreat since the 1980s. Dense populations of Saccorhiza polyschides, the most important species, and Laminaria ochroleuca have been reduced to small patches and isolated individuals east of Peñas Cape (43° 39.4′ N; 5° 50.8′ W). The long-term study of Saccorhiza polyschides populations showed a collapse in the growth of the sporophyte and very low recruitment from the beginning of this century. The possible causal factors of this population decline and its consequences are considered, suggesting that long warm summer periods (more than 30 consecutive days of seawater temperature?>?20°C) could alter kelp performance. 相似文献
979.
Genetic containment of forest plantations 总被引:2,自引:0,他引:2
Amy M. Brunner Jingyi Li Stephen P. DiFazio Olga Shevchenko Brooke E. Montgomery Rozi Mohamed Hao Wei Cathleen Ma Ani Anna Elias Katherine VanWormer Steven H. Strauss 《Tree Genetics & Genomes》2007,3(2):75-100
Dispersal of pollen, seeds, or vegetative propagules from intensively bred, exotic, or recombinant DNA modified forest plantations
may cause detrimental or beneficial ecological impacts on wild or managed ecosystems. Insertion of genes designed to prevent
or substantially reduce dispersal could reduce the risk and extent of undesired impacts. Containment measures may also be
required by law or marketplace constraints, regardless of risks or benefits. We discuss: (1) the context for when genetic
containment or mitigation systems may be needed; (2) technology approaches and mechanisms; (3) the state of knowledge on genes/genomics
of sexual reproduction in forest trees; (4) stability of transgene expression during vegetative growth; (5) simulation studies
to define the level of containment needed; and (6) needed research to deliver effective containment technologies. We illustrate
progress with several examples from our research on recombinant DNA modified poplars. Our simulations show that even partial
sterility can provide very substantial reductions in gene flow into wild trees. We conclude that it is impossible to define
the most effective containment approaches, nor their reliability, based on current genomic knowledge and technological tools.
Additional genomic and technological studies of a wide variety of options are needed. Studies in field environments are essential
to provide data relevant to ecological analysis and regulatory decisions and need to be carried out in phylogenetically diverse
representatives of the economically most important taxa of forest trees.
相似文献
Steven H. StraussEmail: |
980.
Four aromatic amines 1-amino-4-phenoxybenzene (A1), 4-(4-aminophenyloxy) biphenyl (A2), 1-(4-aminophenoxy) naphthalene (A3) and 2-(4-aminophenoxy) naphthalene (A4) were synthesized and characterized by elemental, spectroscopic (FTIR, NMR), mass spectrometric and single crystal X-ray diffraction methods. The compounds crystallized in monoclinic crystal system with space group P21. Intermolecular hydrogen bonds were observed between the amine group and amine/ether acceptors of neighboring molecules. Electrochemical investigations were done using cyclic voltammetry (CV), square wave voltammetry (SWV) and differential pulse voltammetry (DPV). CV studies showed that oxidation of aromatic amines takes place at about 0.9 V (vs. Ag/AgCl) and the electron transfer (ET) process has irreversible nature. After first scan reactive intermediate were generated electrochemically and some other cathodic and anodic peaks also appeared in the succeeding scans. DPV study revealed that ET process is accompanied by one electron. DNA binding study of aromatic amines was performed by CV and UV–visible spectroscopy. These investigations revealed groove binding mode of interaction of aromatic amines with DNA. 相似文献