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排序方式: 共有175条查询结果,搜索用时 15 毫秒
141.
142.
A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer 总被引:28,自引:0,他引:28
Hunter DJ Kraft P Jacobs KB Cox DG Yeager M Hankinson SE Wacholder S Wang Z Welch R Hutchinson A Wang J Yu K Chatterjee N Orr N Willett WC Colditz GA Ziegler RG Berg CD Buys SS McCarty CA Feigelson HS Calle EE Thun MJ Hayes RB Tucker M Gerhard DS Fraumeni JF Hoover RN Thomas G Chanock SJ 《Nature genetics》2007,39(7):870-874
We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci. 相似文献
143.
144.
Indirect radiative forcing of climate change through ozone effects on the land-carbon sink 总被引:5,自引:0,他引:5
The evolution of the Earth's climate over the twenty-first century depends on the rate at which anthropogenic carbon dioxide emissions are removed from the atmosphere by the ocean and land carbon cycles. Coupled climate-carbon cycle models suggest that global warming will act to limit the land-carbon sink, but these first generation models neglected the impacts of changing atmospheric chemistry. Emissions associated with fossil fuel and biomass burning have acted to approximately double the global mean tropospheric ozone concentration, and further increases are expected over the twenty-first century. Tropospheric ozone is known to damage plants, reducing plant primary productivity and crop yields, yet increasing atmospheric carbon dioxide concentrations are thought to stimulate plant primary productivity. Increased carbon dioxide and ozone levels can both lead to stomatal closure, which reduces the uptake of either gas, and in turn limits the damaging effect of ozone and the carbon dioxide fertilization of photosynthesis. Here we estimate the impact of projected changes in ozone levels on the land-carbon sink, using a global land carbon cycle model modified to include the effect of ozone deposition on photosynthesis and to account for interactions between ozone and carbon dioxide through stomatal closure. For a range of sensitivity parameters based on manipulative field experiments, we find a significant suppression of the global land-carbon sink as increases in ozone concentrations affect plant productivity. In consequence, more carbon dioxide accumulates in the atmosphere. We suggest that the resulting indirect radiative forcing by ozone effects on plants could contribute more to global warming than the direct radiative forcing due to tropospheric ozone increases. 相似文献
145.
Eeles RA Kote-Jarai Z Giles GG Olama AA Guy M Jugurnauth SK Mulholland S Leongamornlert DA Edwards SM Morrison J Field HI Southey MC Severi G Donovan JL Hamdy FC Dearnaley DP Muir KR Smith C Bagnato M Ardern-Jones AT Hall AL O'Brien LT Gehr-Swain BN Wilkinson RA Cox A Lewis S Brown PM Jhavar SG Tymrakiewicz M Lophatananon A Bryant SL;UK Genetic Prostate Cancer Study Collaborators;British Association of Urological Surgeons' Section of Oncology;UK ProtecT Study Collaborators Horwich A Huddart RA 《Nature genetics》2008,40(3):316-321
Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at =60 years or with a family history of disease, and 1,894 population-screened controls with a low prostate-specific antigen (PSA) concentration (<0.5 ng/ml). We analyzed these samples for 541,129 SNPs using the Illumina Infinium platform. Initial putative associations were confirmed using a further 3,268 cases and 3,366 controls. We identified seven loci associated with prostate cancer on chromosomes 3, 6, 7, 10, 11, 19 and X (P = 2.7 x 10(-8) to P = 8.7 x 10(-29)). We confirmed previous reports of common loci associated with prostate cancer at 8q24 and 17q. Moreover, we found that three of the newly identified loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK3. 相似文献
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147.
Cox A Dunning AM Garcia-Closas M Balasubramanian S Reed MW Pooley KA Scollen S Baynes C Ponder BA Chanock S Lissowska J Brinton L Peplonska B Southey MC Hopper JL McCredie MR Giles GG Fletcher O Johnson N dos Santos Silva I Gibson L Bojesen SE Nordestgaard BG Axelsson CK Torres D Hamann U Justenhoven C Brauch H Chang-Claude J Kropp S Risch A Wang-Gohrke S Schürmann P Bogdanova N Dörk T Fagerholm R Aaltonen K Blomqvist C Nevanlinna H Seal S Renwick A Stratton MR Rahman N Sangrajrang S Hughes D 《Nature genetics》2007,39(3):352-358
The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies. 相似文献
148.
James TY Kauff F Schoch CL Matheny PB Hofstetter V Cox CJ Celio G Gueidan C Fraker E Miadlikowska J Lumbsch HT Rauhut A Reeb V Arnold AE Amtoft A Stajich JE Hosaka K Sung GH Johnson D O'Rourke B Crockett M Binder M Curtis JM Slot JC Wang Z Wilson AW Schüssler A Longcore JE O'Donnell K Mozley-Standridge S Porter D Letcher PM Powell MJ Taylor JW White MM Griffith GW Davies DR Humber RA Morton JB Sugiyama J Rossman AY Rogers JD Pfister DH Hewitt D Hansen K Hambleton S Shoemaker RA Kohlmeyer J 《Nature》2006,443(7113):818-822
The ancestors of fungi are believed to be simple aquatic forms with flagellated spores, similar to members of the extant phylum Chytridiomycota (chytrids). Current classifications assume that chytrids form an early-diverging clade within the kingdom Fungi and imply a single loss of the spore flagellum, leading to the diversification of terrestrial fungi. Here we develop phylogenetic hypotheses for Fungi using data from six gene regions and nearly 200 species. Our results indicate that there may have been at least four independent losses of the flagellum in the kingdom Fungi. These losses of swimming spores coincided with the evolution of new mechanisms of spore dispersal, such as aerial dispersal in mycelial groups and polar tube eversion in the microsporidia (unicellular forms that lack mitochondria). The enigmatic microsporidia seem to be derived from an endoparasitic chytrid ancestor similar to Rozella allomycis, on the earliest diverging branch of the fungal phylogenetic tree. 相似文献
149.
Gieger C Radhakrishnan A Cvejic A Tang W Porcu E Pistis G Serbanovic-Canic J Elling U Goodall AH Labrune Y Lopez LM Mägi R Meacham S Okada Y Pirastu N Sorice R Teumer A Voss K Zhang W Ramirez-Solis R Bis JC Ellinghaus D Gögele M Hottenga JJ Langenberg C Kovacs P O'Reilly PF Shin SY Esko T Hartiala J Kanoni S Murgia F Parsa A Stephens J van der Harst P Ellen van der Schoot C Allayee H Attwood A Balkau B Bastardot F Basu S Baumeister SE Biino G Bomba L Bonnefond A Cambien F Chambers JC Cucca F 《Nature》2011,480(7376):201-208
Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. 相似文献
150.
De Fazio S Bartonicek N Di Giacomo M Abreu-Goodger C Sankar A Funaya C Antony C Moreira PN Enright AJ O'Carroll D 《Nature》2011,480(7376):259-263
Piwi proteins and Piwi-interacting RNAs (piRNAs) have conserved functions in transposon silencing. The murine Piwi proteins Mili and Miwi2 (also called Piwil2 and Piwil4, respectively) direct epigenetic LINE1 and intracisternal A particle transposon silencing during genome reprogramming in the embryonic male germ line. Piwi proteins are proposed to be piRNA-guided endonucleases that initiate secondary piRNA biogenesis; however, the actual contribution of their endonuclease activities to piRNA biogenesis and transposon silencing remain unknown. To investigate the role of Piwi-catalysed endonucleolytic activity, we engineered point mutations in mice that substitute the second aspartic acid to an alanine in the DDH catalytic triad of Mili and Miwi2, generating the Mili(DAH) and Miwi2(DAH) alleles, respectively. Analysis of Mili-bound piRNAs from homozygous Mili(DAH) fetal gonadocytes revealed a failure of transposon piRNA amplification, resulting in the marked reduction of piRNA bound within Miwi2 ribonuclear particles. We find that Mili-mediated piRNA amplification is selectively required for LINE1, but not intracisternal A particle, silencing. The defective piRNA pathway in Mili(DAH) mice results in spermatogenic failure and sterility. Surprisingly, homozygous Miwi2(DAH) mice are fertile, transposon silencing is established normally and no defects in secondary piRNA biogenesis are observed. In addition, the hallmarks of piRNA amplification are observed in Miwi2-deficient gonadocytes. We conclude that cycles of intra-Mili secondary piRNA biogenesis fuel piRNA amplification that is absolutely required for LINE1 silencing. 相似文献