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排序方式: 共有626条查询结果,搜索用时 15 毫秒
551.
Yang J Manolio TA Pasquale LR Boerwinkle E Caporaso N Cunningham JM de Andrade M Feenstra B Feingold E Hayes MG Hill WG Landi MT Alonso A Lettre G Lin P Ling H Lowe W Mathias RA Melbye M Pugh E Cornelis MC Weir BS Goddard ME Visscher PM 《Nature genetics》2011,43(6):519-525
We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ~45%, ~17%, ~25% and ~21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ~0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein. 相似文献
552.
Mavrakis KJ Van Der Meulen J Wolfe AL Liu X Mets E Taghon T Khan AA Setty M Setti M Rondou P Vandenberghe P Delabesse E Benoit Y Socci NB Leslie CS Van Vlierberghe P Speleman F Wendel HG 《Nature genetics》2011,43(7):673-678
The importance of individual microRNAs (miRNAs) has been established in specific cancers. However, a comprehensive analysis of the contribution of miRNAs to the pathogenesis of any specific cancer is lacking. Here we show that in T-cell acute lymphoblastic leukemia (T-ALL), a small set of miRNAs is responsible for the cooperative suppression of several tumor suppressor genes. Cross-comparison of miRNA expression profiles in human T-ALL with the results of an unbiased miRNA library screen allowed us to identify five miRNAs (miR-19b, miR-20a, miR-26a, miR-92 and miR-223) that are capable of promoting T-ALL development in a mouse model and which account for the majority of miRNA expression in human T-ALL. Moreover, these miRNAs produce overlapping and cooperative effects on tumor suppressor genes implicated in the pathogenesis of T-ALL, including IKAROS (also known as IKZF1), PTEN, BIM, PHF6, NF1 and FBXW7. Thus, a comprehensive and unbiased analysis of miRNA action in T-ALL reveals a striking pattern of miRNA-tumor suppressor gene interactions in this cancer. 相似文献
553.
Conrad DF Keebler JE DePristo MA Lindsay SJ Zhang Y Casals F Idaghdour Y Hartl CL Torroja C Garimella KV Zilversmit M Cartwright R Rouleau GA Daly M Stone EA Hurles ME Awadalla P; Genomes Project 《Nature genetics》2011,43(7):712-714
J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline. Diverse studies have supported Haldane's contention of a higher average mutation rate in the male germline in a variety of mammals, including humans. Here we present, to our knowledge, the first direct comparative analysis of male and female germline mutation rates from the complete genome sequences of two parent-offspring trios. Through extensive validation, we identified 49 and 35 germline de novo mutations (DNMs) in two trio offspring, as well as 1,586 non-germline DNMs arising either somatically or in the cell lines from which the DNA was derived. Most strikingly, in one family, we observed that 92% of germline DNMs were from the paternal germline, whereas, in contrast, in the other family, 64% of DNMs were from the maternal germline. These observations suggest considerable variation in mutation rates within and between families. 相似文献
554.
Passive transfer of resistance in rabbits infested with adultIxodes ricinus L.: Humoral factors influence feeding and egg laying 总被引:1,自引:0,他引:1
Summary Partial immunity against the bites of I. ricinus was transferred to normal rabbits by inoculating immune serum from resistant animals. Transferred humoral factors diminished the weight f the ticks' blood meal by 29% and increased the feeding period by about 1 day in comparison with ectoparasites engorged on controls. They provoked also the failure of egg laying by I. ricinus. Only 55% of ticks fed on treated rabbits laid eggs (94% on controls). The immunological state of immune serum donors or recipients was studied and the IgG and homocytotropic specific anti-I. ricinus antibodies were identified. The immediate hypersensitivity of rabbits' skin was also controlled.The present work was supported by the Swiss National Fund for Scientific Research, grant No. 3.558.75. 相似文献
555.
本文研究了具有复合型吸附剂材料的除湿轮中传热传质耦合现象.采用一种新的隐式差分法模拟除湿轮中的传热传质过程.除湿轮性能取决于旋转速度、基体的传热传质系数、基体水分扩散率、基体热容量和吸附热.计算结果表明:转速是优化除湿轮性能的关键参数;基体传热传质系数越大,除湿性能越好,但当基体表面传热系数大于0.08kW/(m2·K)时,即使再增加传热系数也无法进一步提高除湿效果;吸附热或基体热容越大,除湿轮性能越差. 相似文献
556.
Invasive alien plants have long been recognized as a threat to low-elevation, disturbed environments, but the case of Linaria vulgaris Mill. in Yellowstone National Park and Gallatin National Forest shows that invasions can also spread to high-elevation natural reserves. Because invasions in protected areas are a product of complex processes occurring over a broad range of scales, we argue that a multi-scale research approach is needed to capture both patterns and potential mechanisms of the invasion process. Mapping L. vulgaris at the landscape scale, we found the species occupying a broad range of sites, apparently originating from just 2 historical sources, colonizing both human-caused and natural disturbances. Analyzed at the stand scale, patches tend to aggregate in newly invaded areas and disperse in heavily infested areas. The data suggest that patches grow in size by clonal growth and in number by creation of new satellite patches. Radial patch growth rates are related to site characteristics. Clonal patch scale analysis shows that ramet densities and Linaria 's effects on native plants are highest in patch centers. Both mean ramet height and reproductive vs. vegetative ramet height ratio are higher in patch cores. These results suggest that L. vulgaris may displace natural vegetation by maintaining vigor even in large and old clonal patches. Our results confirm that L. vulgaris is a significant threat to native biodiversity in open, human- or naturally disturbed environments in protected areas of the Rocky Mountains. A multi-scale method can allow managers to better understand patterns of invasion and prioritize management activities to control invasive alien plants, especially in heterogeneous protected area landscapes. 相似文献
557.
根治与遗传有关的疾病是人类基因组计划的主要目标之一。在本文中,美国科普作家埃里克·S·肝格雷斯向您介绍什么是基因疗法以及基因疗法的发展方向。人类基因组计划是一项规模宏大的计划,其目的是要给人类DNA中100,000多个基因绘制图道并对它们进行序列测定。这是一项极其艰巨的任务,自1986以来,已有数百名科学家在世界各地的实验室里为之而奋斗着。最早得以鉴定的人类基因是那些眼疾病──如囊性纤维变性──有关的基因,那是早在对年代的事情了。对整个基因组(即存在于一套完整的染色体中的全部基因)进行序列测定是出于这样的愿… 相似文献
558.
Major histocompatibility complex (MHC) class I molecules present peptides that are derived from endogenous proteins. These antigens can also be transferred to professional antigen-presenting cells in a process called cross-presentation, which precedes initiation of a proper T-cell response; but exactly how they do this is unclear. We tested whether peptides can be transferred directly from the cytoplasm of one cell into the cytoplasm of its neighbour through gap junctions. Here we show that peptides with a relative molecular mass of up to approximately 1,800 diffuse intercellularly through gap junctions unless a three-dimensional structure is imposed. This intercellular peptide transfer causes cytotoxic T-cell recognition of adjacent, innocent bystander cells as well as activated monocytes. Gap-junction-mediated peptide transfer is restricted to a few coupling cells owing to the high cytosolic peptidase activity. We present a mechanism of antigen acquisition for cross-presentation that couples the antigen presentation system of two adjacent cells and is lost in most tumours: gap-junction-mediated intercellular peptide coupling for presentation by bystander MHC class I molecules and transfer to professional antigen presenting cells for cross-priming. 相似文献
559.
Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position 总被引:36,自引:0,他引:36
B lymphocytes re-circulate between B-cell-rich compartments (follicles or B zones) in secondary lymphoid organs, surveying for antigen. After antigen binding, B cells move to the boundary of B and T zones to interact with T-helper cells. Despite the importance of B--T-cell interactions for the induction of antibody responses, the mechanism causing B-cell movement to the T zone has not been defined. Here we show that antigen-engaged B cells have increased expression of CCR7, the receptor for the T-zone chemokines CCL19 and CCL21, and that they exhibit increased responsiveness to both chemoattractants. In mice lacking lymphoid CCL19 and CCL21 chemokines, or with B cells that lack CCR7, antigen engagement fails to cause movement to the T zone. Using retroviral-mediated gene transfer we demonstrate that increased expression of CCR7 is sufficient to direct B cells to the T zone. Reciprocally, overexpression of CXCR5, the receptor for the B-zone chemokine CXCL13, is sufficient to overcome antigen-induced B-cell movement to the T zone. These findings define the mechanism of B-cell relocalization in response to antigen, and establish that cell position in vivo can be determined by the balance of responsiveness to chemoattractants made in separate but adjacent zones. 相似文献
560.
During embryonic development, orderly patterns of gene expression eventually assign each cell in the embryo its particular fate. For the anteroposterior axis of the Drosophila embryo, the first step in this process depends on a spatial gradient of the maternal morphogen Bicoid (Bcd). Positional information of this gradient is transmitted to downstream gap genes, each occupying a well defined spatial domain. We determined the precision of the initial process by comparing expression domains in different embryos. Here we show that the Bcd gradient displays a high embryo-to-embryo variability, but that this noise in the positional information is strongly decreased ('filtered') at the level of hunchback (hb) gene expression. In contrast to the Bcd gradient, the hb expression pattern already includes the information about the scale of the embryo. We show that genes known to interact directly with Hb are not responsible for its spatial precision, but that the maternal gene staufen may be crucial. 相似文献