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排序方式: 共有350条查询结果,搜索用时 15 毫秒
91.
Sun L Rommens JM Corvol H Li W Li X Chiang TA Lin F Dorfman R Busson PF Parekh RV Zelenika D Blackman SM Corey M Doshi VK Henderson L Naughton KM O'Neal WK Pace RG Stonebraker JR Wood SD Wright FA Zielenski J Clement A Drumm ML Boëlle PY Cutting GR Knowles MR Durie PR Strug LJ 《Nature genetics》2012,44(5):562-569
Variants associated with meconium ileus in cystic fibrosis were identified in 3,763 affected individuals by genome-wide association study (GWAS). Five SNPs at two loci near SLC6A14 at Xq23-24 (minimum P = 1.28 × 10(-12) at rs3788766) and SLC26A9 at 1q32.1 (minimum P = 9.88 × 10(-9) at rs4077468) accounted for ~5% of phenotypic variability and were replicated in an independent sample of affected individuals (n = 2,372; P = 0.001 and 0.0001, respectively). By incorporating the knowledge that disease-causing mutations in CFTR alter electrolyte and fluid flux across surface epithelium into a hypothesis-driven GWAS (GWAS-HD), we identified associations with the same SNPs in SLC6A14 and SLC26A9 and established evidence for the involvement of SNPs in a third solute carrier gene, SLC9A3. In addition, GWAS-HD provided evidence of association between meconium ileus and multiple genes encoding constituents of the apical plasma membrane where CFTR resides (P = 0.0002; testing of 155 apical membrane genes jointly and in replication, P = 0.022). These findings suggest that modulating activities of apical membrane constituents could complement current therapeutic paradigms for cystic fibrosis. 相似文献
92.
Brown KM Macgregor S Montgomery GW Craig DW Zhao ZZ Iyadurai K Henders AK Homer N Campbell MJ Stark M Thomas S Schmid H Holland EA Gillanders EM Duffy DL Maskiell JA Jetann J Ferguson M Stephan DA Cust AE Whiteman D Green A Olsson H Puig S Ghiorzo P Hansson J Demenais F Goldstein AM Gruis NA Elder DE Bishop JN Kefford RF Giles GG Armstrong BK Aitken JF Hopper JL Martin NG Trent JM Mann GJ Hayward NK 《Nature genetics》2008,40(7):838-840
We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases. 相似文献
93.
A phenylalanine in DGAT is a key determinant of oil content and composition in maize 总被引:9,自引:0,他引:9
Zheng P Allen WB Roesler K Williams ME Zhang S Li J Glassman K Ranch J Nubel D Solawetz W Bhattramakki D Llaca V Deschamps S Zhong GY Tarczynski MC Shen B 《Nature genetics》2008,40(3):367-372
Plant oil is an important renewable resource for biodiesel production and for dietary consumption by humans and livestock. Through genetic mapping of the oil trait in plants, studies have reported multiple quantitative trait loci (QTLs) with small effects, but the molecular basis of oil QTLs remains largely unknown. Here we show that a high-oil QTL (qHO6) affecting maize seed oil and oleic-acid contents encodes an acyl-CoA:diacylglycerol acyltransferase (DGAT1-2), which catalyzes the final step of oil synthesis. We further show that a phenylalanine insertion in DGAT1-2 at position 469 (F469) is responsible for the increased oil and oleic-acid contents. The DGAT1-2 allele with F469 is ancestral, whereas the allele without F469 is a more recent mutant selected by domestication or breeding. Ectopic expression of the high-oil DGAT1-2 allele increases oil and oleic-acid contents by up to 41% and 107%, respectively. This work provides insights into the molecular basis of natural variation of oil and oleic-acid contents in plants and highlights DGAT as a promising target for increasing oil and oleic-acid contents in other crops. 相似文献
94.
Zusammenfassung Mit Hilfe von radioaktiv markiertem Prolin wird autoradiographisch das Vorkommen von Collagen im Matrixeiweiss pflanzlicher Zellkerne festgestellt.
This investigation was partially supported by a Ford Foundation Grant to the Department of Agricultural Engineering of this Institute. Thanks are due to Prof.V. N. Prasad, Director, and Prof.A. C. Pandya, Head of the Department of Agricultural Engineering of this Institute. 相似文献
This investigation was partially supported by a Ford Foundation Grant to the Department of Agricultural Engineering of this Institute. Thanks are due to Prof.V. N. Prasad, Director, and Prof.A. C. Pandya, Head of the Department of Agricultural Engineering of this Institute. 相似文献
95.
96.
Cattle movements and bovine tuberculosis in Great Britain 总被引:1,自引:0,他引:1
For 20 years, bovine tuberculosis (BTB) has been spreading in Great Britain (England, Wales and Scotland) and is now endemic in the southwest and parts of central England and in southwest Wales, and occurs sporadically elsewhere. Although its transmission pathways remain poorly understood, the disease's distribution was previously modelled statistically by using environmental variables and measures of their seasonality. Movements of infected animals have long been considered a critical factor in the spread of livestock diseases, as reflected in strict import/export regulations, the extensive movement restrictions imposed during the 2001 foot-and-mouth disease outbreak, the tracing procedures after a new case of BTB has been confirmed and the Government's recently published strategic framework for the sustainable control on BTB. Since January 2001 it has been mandatory for stock-keepers in Great Britain to notify the British Cattle Movement Service of all cattle births, movements and deaths. Here we show that movements as recorded in the Cattle Tracing System data archive, and particularly those from areas where BTB is reported, consistently outperform environmental, topographic and other anthropogenic variables as the main predictor of disease occurrence. Simulation distribution models for 2002 and 2003, incorporating all predictor categories, are presented and used to project distributions for 2004 and 2005. 相似文献
97.
Forecasts of climate change are inevitably uncertain. It is therefore essential to quantify the risk of significant departures from the predicted response to a given emission scenario. Previous analyses of this risk have been based either on expert opinion, perturbation analysis of simplified climate models or the comparison of predictions from general circulation models. Recent observed changes that appear to be attributable to human influence provide a powerful constraint on the uncertainties in multi-decadal forecasts. Here we assess the range of warming rates over the coming 50 years that are consistent with the observed near-surface temperature record as well as with the overall patterns of response predicted by several general circulation models. We expect global mean temperatures in the decade 2036-46 to be 1-2.5 K warmer than in pre-industrial times under a 'business as usual' emission scenario. This range is relatively robust to errors in the models' climate sensitivity, rate of oceanic heat uptake or global response to sulphate aerosols as long as these errors are persistent over time. Substantial changes in the current balance of greenhouse warming and sulphate aerosol cooling would, however, increase the uncertainty. Unlike 50-year warming rates, the final equilibrium warming after the atmospheric composition stabilizes remains very uncertain, despite the evidence provided by the emerging signal. 相似文献
98.
Brassins--a new family of plant hormones from rape pollen 总被引:26,自引:0,他引:26
99.
Cellular basis of the immunological defects in thymectomized mice 总被引:17,自引:0,他引:17
100.