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91.
Malek RL Wang HY Kwitek AE Greene AS Bhagabati N Borchardt G Cahill L Currier T Frank B Fu X Hasinoff M Howe E Letwin N Luu TV Saeed A Sajadi H Salzberg SL Sultana R Thiagarajan M Tsai J Veratti K White J Quackenbush J Jacob HJ Lee NH 《Nature genetics》2006,38(2):234-239
Cardiovascular disorders are influenced by genetic and environmental factors. The TIGR rodent expression web-based resource (TREX) contains over 2,200 microarray hybridizations, involving over 800 animals from 18 different rat strains. These strains comprise genetically diverse parental animals and a panel of chromosomal substitution strains derived by introgressing individual chromosomes from normotensive Brown Norway (BN/NHsdMcwi) rats into the background of Dahl salt sensitive (SS/JrHsdMcwi) rats. The profiles document gene-expression changes in both genders, four tissues (heart, lung, liver, kidney) and two environmental conditions (normoxia, hypoxia). This translates into almost 400 high-quality direct comparisons (not including replicates) and over 100,000 pairwise comparisons. As each individual chromosomal substitution strain represents on average less than a 5% change from the parental genome, consomic strains provide a useful mechanism to dissect complex traits and identify causative genes. We performed a variety of data-mining manipulations on the profiles and used complementary physiological data from the PhysGen resource to demonstrate how TREX can be used by the cardiovascular community for hypothesis generation. 相似文献
92.
93.
Herzberg RD Greenlees PT Butler PA Jones GD Venhart M Darby IG Eeckhaudt S Eskola K Grahn T Gray-Jones C Hessberger FP Jones P Julin R Juutinen S Ketelhut S Korten W Leino M Leppänen AP Moon S Nyman M Page RD Pakarinen J Pritchard A Rahkila P Sarén J Scholey C Steer A Sun Y Theisen Ch Uusitalo J 《Nature》2006,442(7105):896-899
A long-standing prediction of nuclear models is the emergence of a region of long-lived, or even stable, superheavy elements beyond the actinides. These nuclei owe their enhanced stability to closed shells in the structure of both protons and neutrons. However, theoretical approaches to date do not yield consistent predictions of the precise limits of the 'island of stability'; experimental studies are therefore crucial. The bulk of experimental effort so far has been focused on the direct creation of superheavy elements in heavy ion fusion reactions, leading to the production of elements up to proton number Z = 118 (refs 4, 5). Recently, it has become possible to make detailed spectroscopic studies of nuclei beyond fermium (Z = 100), with the aim of understanding the underlying single-particle structure of superheavy elements. Here we report such a study of the nobelium isotope 254No, with 102 protons and 152 neutrons--the heaviest nucleus studied in this manner to date. We find three excited structures, two of which are isomeric (metastable). One of these structures is firmly assigned to a two-proton excitation. These states are highly significant as their location is sensitive to single-particle levels above the gap in shell energies predicted at Z = 114, and thus provide a microscopic benchmark for nuclear models of the superheavy elements. 相似文献
94.
Cooper GM Coe BP Girirajan S Rosenfeld JA Vu TH Baker C Williams C Stalker H Hamid R Hannig V Abdel-Hamid H Bader P McCracken E Niyazov D Leppig K Thiese H Hummel M Alexander N Gorski J Kussmann J Shashi V Johnson K Rehder C Ballif BC Shaffer LG Eichler EE 《Nature genetics》2011,43(9):838-846
To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that ~14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders. 相似文献
95.
Albers CA Paul DS Schulze H Freson K Stephens JC Smethurst PA Jolley JD Cvejic A Kostadima M Bertone P Breuning MH Debili N Deloukas P Favier R Fiedler J Hobbs CM Huang N Hurles ME Kiddle G Krapels I Nurden P Ruivenkamp CA Sambrook JG Smith K Stemple DL Strauss G Thys C van Geet C Newbury-Ecob R Ouwehand WH Ghevaert C 《Nature genetics》2012,44(4):435-9, S1-2
96.
A high-resolution survey of deletion polymorphism in the human genome 总被引:20,自引:0,他引:20
Recent work has shown that copy number polymorphism is an important class of genetic variation in human genomes. Here we report a new method that uses SNP genotype data from parent-offspring trios to identify polymorphic deletions. We applied this method to data from the International HapMap Project to produce the first high-resolution population surveys of deletion polymorphism. Approximately 100 of these deletions have been experimentally validated using comparative genome hybridization on tiling-resolution oligonucleotide microarrays. Our analysis identifies a total of 586 distinct regions that harbor deletion polymorphisms in one or more of the families. Notably, we estimate that typical individuals are hemizygous for roughly 30-50 deletions larger than 5 kb, totaling around 550-750 kb of euchromatic sequence across their genomes. The detected deletions span a total of 267 known and predicted genes. Overall, however, the deleted regions are relatively gene-poor, consistent with the action of purifying selection against deletions. Deletion polymorphisms may well have an important role in the genetics of complex traits; however, they are not directly observed in most current gene mapping studies. Our new method will permit the identification of deletion polymorphisms in high-density SNP surveys of trio or other family data. 相似文献
97.
Francis H Chapelle Kathleen O'Neill Paul M Bradley Barbara A Methé Stacy A Ciufo LeRoy L Knobel Derek R Lovley 《Nature》2002,415(6869):312-315
The search for extraterrestrial life may be facilitated if ecosystems can be found on Earth that exist under conditions analogous to those present on other planets or moons. It has been proposed, on the basis of geochemical and thermodynamic considerations, that geologically derived hydrogen might support subsurface microbial communities on Mars and Europa in which methanogens form the base of the ecosystem. Here we describe a unique subsurface microbial community in which hydrogen-consuming, methane-producing Archaea far outnumber the Bacteria. More than 90% of the 16S ribosomal DNA sequences recovered from hydrothermal waters circulating through deeply buried igneous rocks in Idaho are related to hydrogen-using methanogenic microorganisms. Geochemical characterization indicates that geothermal hydrogen, not organic carbon, is the primary energy source for this methanogen-dominated microbial community. These results demonstrate that hydrogen-based methanogenic communities do occur in Earth's subsurface, providing an analogue for possible subsurface microbial ecosystems on other planets. 相似文献
98.
99.
Of the 13 lakes in the central Wasatch Mountains with tiger salamander ( Ambystoma tigrinum ) populations, salamander mass mortalities occurred in four seepage lakes that experienced extensive lowering of the water levels during the summer. The largest of these lakes, the oligotrophic Desolation Lake, was studied to determine the cause of the mortality phenomenon. The recurrent annual mass mortality involved both breeding adults and young-of-the-year. Rate kinetics suggest that mortality rate doubles with a fivefold increase in the number of aquatic young salamanders. The proximate cause of the mass mortality was identified as a bacterium, Acinetobacter sp. Desolation Lake and a seepage lake that did not experience the mass mortality were studied for the presence of Acinetobacter . Both lakes experienced two bacteria cycles: the first in early summer involved gram-positive bacteria, and the second in late summer involved gram-negative bacteria (mostly coliform bacteria and Acinetobacter ). The mass mortalities were associated with the late-summer gram-negative bacterial bloom, and Acinetobacter was found in large numbers in Desolation Lake. Algae, as well as other photosynthetic plants, were not present in large numbers. Since these lakes are growth-limited with respect to nitrogen and not with respect to phosphate, and since Desolation Lake had extensive lowering of the lake level during the summer, the biological cycle of the lake is proposed to be due to atmospheric and sheep-produced nitrogen products within the watershed. In this unstable lake system, bacteria are primarily responsible for incorporation of nitrogen in the food chain. The timing of the cyclical events depends on total winter precipitation. 相似文献
100.
JingHua Liu PingZhong Zhang Hai Cheng FaHu Chen XunLin Yang DeZhong Zhang Jing Zhou JiHong Jia ChunLei An WenCui Sang Kathleen R. Johnson 《科学通报(英文版)》2008,53(13):2041-2049
Based on 5 high-precision ^230Th dates and 103 stable oxygen isotope ratios (51eO) obtained from the top 16 mm of a stalagmite collected from Wanxiang Cave, Wudu, Gansu, variation of monsoonal precipitation in the modern Asian Monsoon (AM) marginal zone over the past 100 years was reconstructed. Comparison of the speleothem δ^18O record with instrumental precipitation data at Wudu in the past 50 years indicates a high parallelism between the two curves, suggesting that the speleothem δ^18O is a good proxy for the AM strength and associated precipitation, controlled by "amount effect" of the precipitation. Variation of the monsoonal precipitation during the past 100 years can be divided into three stages, increasing from AD 1875 to 1900, then decreasing from AD 1901 to 1946, and increasing again thereafter. This variation is quite similar to that of the Drought/Flooding index archived from Chinese historical documents. This speleothem-derived AM record shows a close association with the Pacific Decadal Oscillation (PDO) between AD 1875 and 1977, with higher monsoonal precipitation corresponding to cold PDO phase and vice versa at decadal timescale. The monsoonal precipitation variation is out of phase with the PDO after AD 1977, probably resulting from the decadal climate jump in the north Pacific occurring at around AD 1976/77. These results demonstrate a strong linkage between the AM and associated precipitation and the Pacific Ocean via ocean/atmosphere interaction. This relationship will aid to forecast future hydrological cycle for the AM monsoon region, and to improve forecasting potential of climatic model with observation data from cave. 相似文献