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221.
Warren WC Hillier LW Marshall Graves JA Birney E Ponting CP Grützner F Belov K Miller W Clarke L Chinwalla AT Yang SP Heger A Locke DP Miethke P Waters PD Veyrunes F Fulton L Fulton B Graves T Wallis J Puente XS López-Otín C Ordóñez GR Eichler EE Chen L Cheng Z Deakin JE Alsop A Thompson K Kirby P Papenfuss AT Wakefield MJ Olender T Lancet D Huttley GA Smit AF Pask A Temple-Smith P Batzer MA Walker JA Konkel MK Harris RS Whittington CM Wong ES Gemmell NJ Buschiazzo E Vargas Jentzsch IM Merkel A 《Nature》2008,453(7192):175-183
We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation. 相似文献
222.
Intraspecific hybridisation and the release of mutator activity. 总被引:1,自引:0,他引:1
223.
Because quantity and quality of roosting habitat can affect Merriam’s Wild Turkey ( Meleagris gallopavo merriami ) distribution, we described habitat characteristics of Merriam’s turkey roost sites in the southern Black Hills of South Dakota. Varying proportions of Merriam’s turkeys in the southern Black Hills depended on supplemental feed from livestock operations during the 2 winters of our study, whereas the remainder wintered in forested habitat away from supplemental feed. We compared characteristics of roost habitat occupied by female turkeys from both groups. We located turkeys with radio-transmitters in the early morning and late evening to find roost sites. Female Merriam’s turkeys in the southern Black Hills roosted exclusively in ponderosa pine trees, primarily on the upper portions of ridges on easterly aspects. Generally, trees >30 cm diameter at breast height (dbh) were chosen for roosting, but turkeys also roosted in trees with smaller dbh. During winter months, turkeys that relied on supplemental feeding roosted adjacent to the ranch-farmstead where the supplemental food was located. Generally, these turkeys used the same roost site(s) throughout the winter, whereas turkeys that remained in the forest during winter used multiple roost sites. We suggest maintaining stands of trees >30 cm dbh on the upper portions of easterly aspects to provide suitable roosting habitat for female Merriam’s Wild Turkeys in the southern Black Hills. 相似文献
224.
Genome-wide association study identifies a common variant associated with risk of endometrial cancer
Spurdle AB Thompson DJ Ahmed S Ferguson K Healey CS O'Mara T Walker LC Montgomery SB Dermitzakis ET;Australian National Endometrial Cancer Study Group Fahey P Montgomery GW Webb PM Fasching PA Beckmann MW Ekici AB Hein A Lambrechts D Coenegrachts L Vergote I Amant F Salvesen HB Trovik J Njolstad TS Helland H Scott RJ Ashton K Proietto T Otton G;National Study of Endometrial Cancer Genetics Group Tomlinson I Gorman M Howarth K Hodgson S Garcia-Closas M Wentzensen N Yang H Chanock S Hall P 《Nature genetics》2011,43(5):451-454
Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes. 相似文献
225.
226.
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene 总被引:25,自引:0,他引:25
Rahman N Seal S Thompson D Kelly P Renwick A Elliott A Reid S Spanova K Barfoot R Chagtai T Jayatilake H McGuffog L Hanks S Evans DG Eccles D;Breast Cancer Susceptibility Collaboration 《Nature genetics》2007,39(2):165-167
PALB2 interacts with BRCA2, and biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia. We identified monoallelic truncating PALB2 mutations in 10/923 individuals with familial breast cancer compared with 0/1,084 controls (P = 0.0004) and show that such mutations confer a 2.3-fold higher risk of breast cancer (95% confidence interval (c.i.) = 1.4-3.9, P = 0.0025). The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia-DNA repair pathway and breast cancer predisposition. 相似文献
227.
Pietrzyński G Thompson IB Gieren W Graczyk D Stępień K Bono G Moroni PG Pilecki B Udalski A Soszyński I Preston GW Nardetto N McWilliam A Roederer IU Górski M Konorski P Storm J 《Nature》2012,484(7392):75-77
RR Lyrae pulsating stars have been extensively used as tracers of old stellar populations for the purpose of determining the ages of galaxies, and as tools to measure distances to nearby galaxies. There was accordingly considerable interest when the RR Lyrae star OGLE-BLG-RRLYR-02792 (referred to here as RRLYR-02792) was found to be a member of an eclipsing binary system, because the mass of the pulsator (hitherto constrained only by models) could be unambiguously determined. Here we report that RRLYR-02792 has a mass of 0.26 solar masses M[symbol see text] and therefore cannot be a classical RR Lyrae star. Using models, we find that its properties are best explained by the evolution of a close binary system that started with M[symbol see text] and 0.8M[symbol see text]stars orbiting each other with an initial period of 2.9 days. Mass exchange over 5.4 billion years produced the observed system, which is now in a very short-lived phase where the physical properties of the pulsator happen to place it in the same instability strip of the Hertzsprung-Russell diagram as that occupied by RR Lyrae stars. We estimate that only 0.2 per cent of RR Lyrae stars may be contaminated by systems similar to this one, which implies that distances measured with RR Lyrae stars should not be significantly affected by these binary interlopers. 相似文献
228.
Garnett MJ Edelman EJ Heidorn SJ Greenman CD Dastur A Lau KW Greninger P Thompson IR Luo X Soares J Liu Q Iorio F Surdez D Chen L Milano RJ Bignell GR Tam AT Davies H Stevenson JA Barthorpe S Lutz SR Kogera F Lawrence K McLaren-Douglas A Mitropoulos X Mironenko T Thi H Richardson L Zhou W Jewitt F Zhang T O'Brien P Boisvert JL Price S Hur W Yang W Deng X Butler A Choi HG Chang JW Baselga J Stamenkovic I Engelman JA Sharma SV Delattre O Saez-Rodriguez J Gray NS Settleman J Futreal PA Haber DA 《Nature》2012,483(7391):570-575
Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies. 相似文献
229.
230.
IDH mutation impairs histone demethylation and results in a block to cell differentiation 总被引:1,自引:0,他引:1
Lu C Ward PS Kapoor GS Rohle D Turcan S Abdel-Wahab O Edwards CR Khanin R Figueroa ME Melnick A Wellen KE O'Rourke DM Berger SL Chan TA Levine RL Mellinghoff IK Thompson CB 《Nature》2012,483(7390):474-478
Recurrent mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 have been identified in gliomas, acute myeloid leukaemias (AML) and chondrosarcomas, and share a novel enzymatic property of producing 2-hydroxyglutarate (2HG) from α-ketoglutarate. Here we report that 2HG-producing IDH mutants can prevent the histone demethylation that is required for lineage-specific progenitor cells to differentiate into terminally differentiated cells. In tumour samples from glioma patients, IDH mutations were associated with a distinct gene expression profile enriched for genes expressed in neural progenitor cells, and this was associated with increased histone methylation. To test whether the ability of IDH mutants to promote histone methylation contributes to a block in cell differentiation in non-transformed cells, we tested the effect of neomorphic IDH mutants on adipocyte differentiation in vitro. Introduction of either mutant IDH or cell-permeable 2HG was associated with repression of the inducible expression of lineage-specific differentiation genes and a block to differentiation. This correlated with a significant increase in repressive histone methylation marks without observable changes in promoter DNA methylation. Gliomas were found to have elevated levels of similar histone repressive marks. Stable transfection of a 2HG-producing mutant IDH into immortalized astrocytes resulted in progressive accumulation of histone methylation. Of the marks examined, increased H3K9 methylation reproducibly preceded a rise in DNA methylation as cells were passaged in culture. Furthermore, we found that the 2HG-inhibitable H3K9 demethylase KDM4C was induced during adipocyte differentiation, and that RNA-interference suppression of KDM4C was sufficient to block differentiation. Together these data demonstrate that 2HG can inhibit histone demethylation and that inhibition of histone demethylation can be sufficient to block the differentiation of non-transformed cells. 相似文献