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41.
Publish your computer code: it is good enough 总被引:1,自引:0,他引:1
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MJ Emond T Louie J Emerson W Zhao RA Mathias MR Knowles FA Wright MJ Rieder HK Tabor DA Nickerson KC Barnes;National Heart Lung Blood Institute 《Nature genetics》2012,44(8):886-889
Exome sequencing has become a powerful and effective strategy for the discovery of genes underlying Mendelian disorders. However, use of exome sequencing to identify variants associated with complex traits has been more challenging, partly because the sample sizes needed for adequate power may be very large. One strategy to increase efficiency is to sequence individuals who are at both ends of a phenotype distribution (those with extreme phenotypes). Because the frequency of alleles that contribute to the trait are enriched in one or both phenotype extremes, a modest sample size can potentially be used to identify novel candidate genes and/or alleles. As part of the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP), we used an extreme phenotype study design to discover that variants in DCTN4, encoding a dynactin protein, are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis. 相似文献
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Crow YJ Hayward BE Parmar R Robins P Leitch A Ali M Black DN van Bokhoven H Brunner HG Hamel BC Corry PC Cowan FM Frints SG Klepper J Livingston JH Lynch SA Massey RF Meritet JF Michaud JL Ponsot G Voit T Lebon P Bonthron DT Jackson AP Barnes DE Lindahl T 《Nature genetics》2006,38(8):917-920
Aicardi-Goutières syndrome (AGS) presents as a severe neurological brain disease and is a genetic mimic of the sequelae of transplacentally acquired viral infection. Evidence exists for a perturbation of innate immunity as a primary pathogenic event in the disease phenotype. Here, we show that TREX1, encoding the major mammalian 3' --> 5' DNA exonuclease, is the AGS1 gene, and AGS-causing mutations result in abrogation of TREX1 enzyme activity. Similar loss of function in the Trex1(-/-) mouse leads to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response. 相似文献
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McNeil RP Kataoka M Ford CJ Barnes CH Anderson D Jones GA Farrer I Ritchie DA 《Nature》2011,477(7365):439-442
Single-electron circuits of the future, consisting of a network of quantum dots, will require a mechanism to transport electrons from one functional part of the circuit to another. For example, in a quantum computer decoherence and circuit complexity can be reduced by separating quantum bit (qubit) manipulation from measurement and by providing a means of transporting electrons between the corresponding parts of the circuit. Highly controlled tunnelling between neighbouring dots has been demonstrated, and our ability to manipulate electrons in single- and double-dot systems is improving rapidly. For distances greater than a few hundred nanometres, neither free propagation nor tunnelling is viable while maintaining confinement of single electrons. Here we show how a single electron may be captured in a surface acoustic wave minimum and transferred from one quantum dot to a second, unoccupied, dot along a long, empty channel. The transfer direction may be reversed and the same electron moved back and forth more than sixty times-a cumulative distance of 0.25 mm-without error. Such on-chip transfer extends communication between quantum dots to a range that may allow the integration of discrete quantum information processing components and devices. 相似文献
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The major hanging gardens and associated water seeps in Zion National Park were surveyed for the presence of the Zion Snail ( Physa zionis ). Environmental parameters, including water depth, water velocity, substrate slope, and algal cover, were measured to determine their effect on the local distribution of the snail. Large populations (densities 125 to 250/m 2 ) were found in the Virgin River Narrows area of the park and at a hanging garden and seep located 1.0 km north of Scout Lookout. Densities in other localities were low in comparison. Snails were not found in all hanging gardens or seeps. The major factor controlling within seep distribution was determined to be water velocity. Experiments were conducted to test the ability of the snail to remain attached during differing water flows. The snail showed an ability to remain attached during high flows, but few snails were found in areas of high flow. 相似文献
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