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排序方式: 共有141条查询结果,搜索用时 46 毫秒
111.
Budde BS Namavar Y Barth PG Poll-The BT Nürnberg G Becker C van Ruissen F Weterman MA Fluiter K te Beek ET Aronica E van der Knaap MS Höhne W Toliat MR Crow YJ Steinling M Voit T Roelenso F Brussel W Brockmann K Kyllerman M Boltshauser E Hammersen G Willemsen M Basel-Vanagaite L Krägeloh-Mann I de Vries LS Sztriha L Muntoni F Ferrie CD Battini R Hennekam RC Grillo E Beemer FA Stoets LM Wollnik B Nürnberg P Baas F 《Nature genetics》2008,40(9):1113-1118
Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders. 相似文献
112.
Cambon-Thomsen A Thorisson GA Mabile L Andrieu S Bertier G Boeckhout M Cambon-Thomsen A Carpenter J Dagher G Dalgleish R Deschênes M di Donato JH Filocamo M Goldberg M Hewitt R Hofman P Kauffmann F Leitsalu L Lomba I Mabile L Melegh B Metspalu A Miranda L Napolitani F Oestergaard MZ Parodi B Pasterk M Reiche A Rial-Sebbag E Rivalle G Rochaix P Susbielle G Tarasova L Thomsen M Thorisson GA Zawati MH Zins M;BRIF workshop group 《Nature genetics》2011,43(6):503-504
113.
Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia 总被引:1,自引:0,他引:1
Zenatti PP Ribeiro D Li W Zuurbier L Silva MC Paganin M Tritapoe J Hixon JA Silveira AB Cardoso BA Sarmento LM Correia N Toribio ML Kobarg J Horstmann M Pieters R Brandalise SR Ferrando AA Meijerink JP Durum SK Yunes JA Barata JT 《Nature genetics》2011,43(10):932-939
Interleukin 7 (IL-7) and its receptor, formed by IL-7Rα (encoded by IL7R) and γc, are essential for normal T-cell development and homeostasis. Here we show that IL7R is an oncogene mutated in T-cell acute lymphoblastic leukemia (T-ALL). We find that 9% of individuals with T-ALL have somatic gain-of-function IL7R exon 6 mutations. In most cases, these IL7R mutations introduce an unpaired cysteine in the extracellular juxtamembrane-transmembrane region and promote de novo formation of intermolecular disulfide bonds between mutant IL-7Rα subunits, thereby driving constitutive signaling via JAK1 and independently of IL-7, γc or JAK3. IL7R mutations induce a gene expression profile partially resembling that provoked by IL-7 and are enriched in the T-ALL subgroup comprising TLX3 rearranged and HOXA deregulated cases. Notably, IL7R mutations promote cell transformation and tumor formation. Overall, our findings indicate that IL7R mutational activation is involved in human T-cell leukemogenesis, paving the way for therapeutic targeting of IL-7R-mediated signaling in T-ALL. 相似文献
114.
Sansone SA Rocca-Serra P Field D Maguire E Taylor C Hofmann O Fang H Neumann S Tong W Amaral-Zettler L Begley K Booth T Bougueleret L Burns G Chapman B Clark T Coleman LA Copeland J Das S de Daruvar A de Matos P Dix I Edmunds S Evelo CT Forster MJ Gaudet P Gilbert J Goble C Griffin JL Jacob D Kleinjans J Harland L Haug K Hermjakob H Ho Sui SJ Laederach A Liang S Marshall S McGrath A Merrill E Reilly D Roux M Shamu CE Shang CA Steinbeck C Trefethen A Williams-Jones B Wolstencroft K Xenarios I 《Nature genetics》2012,44(2):121-126
To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision. 相似文献
115.
116.
Thomas RK Baker AC Debiasi RM Winckler W Laframboise T Lin WM Wang M Feng W Zander T MacConaill L Macconnaill LE Lee JC Nicoletti R Hatton C Goyette M Girard L Majmudar K Ziaugra L Wong KK Gabriel S Beroukhim R Peyton M Barretina J Dutt A Emery C Greulich H Shah K Sasaki H Gazdar A Minna J Armstrong SA Mellinghoff IK Hodi FS Dranoff G Mischel PS Cloughesy TF Nelson SF Liau LM Mertz K Rubin MA Moch H Loda M Catalona W Fletcher J Signoretti S Kaye F Anderson KC Demetri GD Dummer R Wagner S 《Nature genetics》2007,39(3):347-351
Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention. 相似文献
117.
Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes 总被引:7,自引:0,他引:7
Lowe CE Cooper JD Brusko T Walker NM Smyth DJ Bailey R Bourget K Plagnol V Field S Atkinson M Clayton DG Wicker LS Todd JA 《Nature genetics》2007,39(9):1074-1082
Genome-wide association studies are now identifying disease-associated chromosome regions. However, even after convincing replication, the localization of the causal variant(s) requires comprehensive resequencing, extensive genotyping and statistical analyses in large sample sets leading to targeted functional studies. Here, we have localized the type 1 diabetes (T1D) association in the interleukin 2 receptor alpha (IL2RA) gene region to two independent groups of SNPs, spanning overlapping regions of 14 and 40 kb, encompassing IL2RA intron 1 and the 5' regions of IL2RA and RBM17 (odds ratio = 2.04, 95% confidence interval = 1.70-2.45; P = 1.92 x 10(-28); control frequency = 0.635). Furthermore, we have associated IL2RA T1D susceptibility genotypes with lower circulating levels of the biomarker, soluble IL-2RA (P = 6.28 x 10(-28)), suggesting that an inherited lower immune responsiveness predisposes to T1D. 相似文献
118.
119.
Sebaihia M Wren BW Mullany P Fairweather NF Minton N Stabler R Thomson NR Roberts AP Cerdeño-Tárraga AM Wang H Holden MT Wright A Churcher C Quail MA Baker S Bason N Brooks K Chillingworth T Cronin A Davis P Dowd L Fraser A Feltwell T Hance Z Holroyd S Jagels K Moule S Mungall K Price C Rabbinowitsch E Sharp S Simmonds M Stevens K Unwin L Whithead S Dupuy B Dougan G Barrell B Parkhill J 《Nature genetics》2006,38(7):779-786
We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism. 相似文献
120.
CREBBP mutations in relapsed acute lymphoblastic leukaemia 总被引:2,自引:0,他引:2