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21.
Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome 总被引:1,自引:0,他引:1
Parks AL Cook KR Belvin M Dompe NA Fawcett R Huppert K Tan LR Winter CG Bogart KP Deal JE Deal-Herr ME Grant D Marcinko M Miyazaki WY Robertson S Shaw KJ Tabios M Vysotskaia V Zhao L Andrade RS Edgar KA Howie E Killpack K Milash B Norton A Thao D Whittaker K Winner MA Friedman L Margolis J Singer MA Kopczynski C Curtis D Kaufman TC Plowman GD Duyk G Francis-Lang HL 《Nature genetics》2004,36(3):288-292
In fruit fly research, chromosomal deletions are indispensable tools for mapping mutations, characterizing alleles and identifying interacting loci. Most widely used deletions were generated by irradiation or chemical mutagenesis. These methods are labor-intensive, generate random breakpoints and result in unwanted secondary mutations that can confound phenotypic analyses. Most of the existing deletions are large, have molecularly undefined endpoints and are maintained in genetically complex stocks. Furthermore, the existence of haplolethal or haplosterile loci makes the recovery of deletions of certain regions exceedingly difficult by traditional methods, resulting in gaps in coverage. Here we describe two methods that address these problems by providing for the systematic isolation of targeted deletions in the D. melanogaster genome. The first strategy used a P element-based technique to generate deletions that closely flank haploinsufficient genes and minimize undeleted regions. This deletion set has increased overall genomic coverage by 5-7%. The second strategy used FLP recombinase and the large array of FRT-bearing insertions described in the accompanying paper to generate 519 isogenic deletions with molecularly defined endpoints. This second deletion collection provides 56% genome coverage so far. The latter methodology enables the generation of small custom deletions with predictable endpoints throughout the genome and should make their isolation a simple and routine task. 相似文献
22.
Coltman DW O'Donoghue P Jorgenson JT Hogg JT Strobeck C Festa-Bianchet M 《Nature》2003,426(6967):655-658
Phenotype-based selective harvests, including trophy hunting, can have important implications for sustainable wildlife management if they target heritable traits. Here we show that in an evolutionary response to sport hunting of bighorn trophy rams (Ovis canadensis) body weight and horn size have declined significantly over time. We used quantitative genetic analyses, based on a partly genetically reconstructed pedigree from a 30-year study of a wild population in which trophy hunting targeted rams with rapidly growing horns, to explore the evolutionary response to hunter selection on ram weight and horn size. Both traits were highly heritable, and trophy-harvested rams were of significantly higher genetic 'breeding value' for weight and horn size than rams that were not harvested. Rams of high breeding value were also shot at an early age, and thus did not achieve high reproductive success. Declines in mean breeding values for weight and horn size therefore occurred in response to unrestricted trophy hunting, resulting in the production of smaller-horned, lighter rams, and fewer trophies. 相似文献
23.
The origin of our own genus, Homo, has been tentatively correlated with worldwide climatic cooling documented at about 2.4 Myr (million years). It has also been conjectured that members of Homo made the first stone tools, currently dated at 2.6-2.4 Myr. But fossil specimens clearly attributable to Homo before about 1.9 Myr have been lacking. In 1967 a fossil hominoid temporal bone (KNM-BC1) from the Chemeron Formation of Kenya was described as family Hominidae gen. et sp. indet. Although a surface find, its provenance within site JM85 (BPRP site K002) was established and a stratigraphic section provided indicating the specimen's position. This evidence has been affirmed but the exact age of the fossil was never determined, and the absence of suitable comparative hominid material has precluded a more definitive taxonomic assignment. Here we present 40Ar/39Ar age determinations on material from the hominid site indicating an age of 2.4 Myr. In addition, comparative studies allow us to assign KNM-BC1 to the genus Homo, making it the earliest securely known fossil of our own genus found so far. 相似文献
24.
New class of glutamate agonist structurally related to ibotenic acid 总被引:20,自引:0,他引:20
25.
Acetylcholine sensitivity of cerebellar neurones 总被引:3,自引:0,他引:3
26.
Response of fungi to diurnal temperature extremes 总被引:1,自引:0,他引:1
C R Curtis 《Nature》1967,213(5077):738-739
27.
The role of steroids in promoting cell proliferation is well established but the molecular mechanisms are not clear. The S115 mouse mammary tumour cell line provides a model system for molecular studies in vitro in that it exhibits in tissue culture both a positive proliferative response to androgens and a change from a transformed phenotype in the presence of androgen to a normal phenotype when androgen is removed. We have considered here the possible involvement of mouse mammary tumour virus (MMTV) in these processes. We have demonstrated the presence in S115 cells of MMTV-related sequences which are transcribed into RNA only in the long-term presence of androgen. Prolonged culture in the absence of androgen, which results in loss of proliferative response to androgen, is accompanied by loss of MMTV-related RNA and increased methylation of MMTV-related sequences. 相似文献
28.
The loss of ions from Venus through the plasma wake 总被引:1,自引:0,他引:1
Barabash S Fedorov A Sauvaud JJ Lundin R Russell CT Futaana Y Zhang TL Andersson H Brinkfeldt K Grigoriev A Holmström M Yamauchi M Asamura K Baumjohann W Lammer H Coates AJ Kataria DO Linder DR Curtis CC Hsieh KC Sandel BR Grande M Gunell H Koskinen HE Kallio E Riihelä P Säles T Schmidt W Kozyra J Krupp N Fränz M Woch J Luhmann J McKenna-Lawlor S Mazelle C Thocaven JJ Orsini S Cerulli-Irelli R Mura M Milillo M Maggi M Roelof E Brandt P Szego K Winningham JD Frahm RA Scherrer J Sharber JR Wurz P 《Nature》2007,450(7170):650-653
Venus, unlike Earth, is an extremely dry planet although both began with similar masses, distances from the Sun, and presumably water inventories. The high deuterium-to-hydrogen ratio in the venusian atmosphere relative to Earth's also indicates that the atmosphere has undergone significantly different evolution over the age of the Solar System. Present-day thermal escape is low for all atmospheric species. However, hydrogen can escape by means of collisions with hot atoms from ionospheric photochemistry, and although the bulk of O and O2 are gravitationally bound, heavy ions have been observed to escape through interaction with the solar wind. Nevertheless, their relative rates of escape, spatial distribution, and composition could not be determined from these previous measurements. Here we report Venus Express measurements showing that the dominant escaping ions are O+, He+ and H+. The escaping ions leave Venus through the plasma sheet (a central portion of the plasma wake) and in a boundary layer of the induced magnetosphere. The escape rate ratios are Q(H+)/Q(O+) = 1.9; Q(He+)/Q(O+) = 0.07. The first of these implies that the escape of H+ and O+, together with the estimated escape of neutral hydrogen and oxygen, currently takes place near the stoichometric ratio corresponding to water. 相似文献
29.
Shah SP Roth A Goya R Oloumi A Ha G Zhao Y Turashvili G Ding J Tse K Haffari G Bashashati A Prentice LM Khattra J Burleigh A Yap D Bernard V McPherson A Shumansky K Crisan A Giuliany R Heravi-Moussavi A Rosner J Lai D Birol I Varhol R Tam A Dhalla N Zeng T Ma K Chan SK Griffith M Moradian A Cheng SW Morin GB Watson P Gelmon K Chia S Chin SF Curtis C Rueda OM Pharoah PD Damaraju S Mackey J Hoon K Harkins T Tadigotla V Sigaroudinia M Gascard P Tlsty T Costello JF Meyer IM Eaves CJ Wasserman WW 《Nature》2012,486(7403):395-399
Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes. 相似文献
30.
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups 总被引:1,自引:0,他引:1
Curtis C Shah SP Chin SF Turashvili G Rueda OM Dunning MJ Speed D Lynch AG Samarajiwa S Yuan Y Gräf S Ha G Haffari G Bashashati A Russell R McKinney S;METABRIC Group Langerød A Green A Provenzano E Wishart G Pinder S Watson P Markowetz F Murphy L Ellis I Purushotham A Børresen-Dale AL Brenton JD Tavaré S Caldas C Aparicio S 《Nature》2012,486(7403):346-352