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41.
Big data: The future of biocuration 总被引:2,自引:0,他引:2
Howe D Costanzo M Fey P Gojobori T Hannick L Hide W Hill DP Kania R Schaeffer M St Pierre S Twigger S White O Rhee SY 《Nature》2008,455(7209):47-50
42.
Cloning of a representative genomic library of the human X chromosome after sorting by flow cytometry 总被引:54,自引:0,他引:54
A library of 50,000 recombinants representative of the human X chromosome has been constructed. Human X chromosomes were physically separated using a fluorescence-activated cell sorter. The DNA was purified from the chromosomes, digested to completion with the restriction enzyme EcoRI and cloned into the phage lambda gtWES.lambda B. The X-derived nature of the recombinants was confirmed by hybridization to rodent/human cell line DNA containing only the human X chromosome. Such libraries will be particularly useful for the investigation of genetic diseases such as Duchenne muscular dystrophy, where the basic defect has not been elucidated, and of neoplasia, where several specific chromosomal anomalies, particularly for the leukaemias, have been identified. 相似文献
43.
HIV preferentially infects HIV-specific CD4+ T cells 总被引:34,自引:0,他引:34
Douek DC Brenchley JM Betts MR Ambrozak DR Hill BJ Okamoto Y Casazza JP Kuruppu J Kunstman K Wolinsky S Grossman Z Dybul M Oxenius A Price DA Connors M Koup RA 《Nature》2002,417(6884):95-98
HIV infection is associated with the progressive loss of CD4(+) T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4(+) T cells are preferentially affected. Here we show that HIV-specific memory CD4(+) T cells in infected individuals contain more HIV viral DNA than other memory CD4(+) T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4(+) T cells increases to a greater extent than in memory CD4(+) T cells of other specificities. These findings show that HIV-specific CD4(+) T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4(+) T-cell responses, and consequently the loss of immunological control of HIV replication. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption. 相似文献
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Reboul J Vaglio P Rual JF Lamesch P Martinez M Armstrong CM Li S Jacotot L Bertin N Janky R Moore T Hudson JR Hartley JL Brasch MA Vandenhaute J Boulton S Endress GA Jenna S Chevet E Papasotiropoulos V Tolias PP Ptacek J Snyder M Huang R Chance MR Lee H Doucette-Stamm L Hill DE Vidal M 《Nature genetics》2003,34(1):35-41
To verify the genome annotation and to create a resource to functionally characterize the proteome, we attempted to Gateway-clone all predicted protein-encoding open reading frames (ORFs), or the 'ORFeome,' of Caenorhabditis elegans. We successfully cloned approximately 12,000 ORFs (ORFeome 1.1), of which roughly 4,000 correspond to genes that are untouched by any cDNA or expressed-sequence tag (EST). More than 50% of predicted genes needed corrections in their intron-exon structures. Notably, approximately 11,000 C. elegans proteins can now be expressed under many conditions and characterized using various high-throughput strategies, including large-scale interactome mapping. We suggest that similar ORFeome projects will be valuable for other organisms, including humans. 相似文献
47.
Summary In a survey of the intracellular bile salt oxidoreductase activity in fecal bacteria, 16 strains of nuclear dehydrogenating clostridia and 2 strains of non-nuclear dehydrogenatingC. paraputrificum were demonstrated unable to oxidize cholate at any of the 3 OH groups. Since nuclear dehydrogenation at the -1 and -4 position requires a 3-oxo precursor steroid, it appears that these organisms require the presence of a 3-hydroxysteroid dehydrogenating organism for nuclear dehydrogenation.This work is supported by the National Cancer Institute of Canada (IAM) and by the Cancer Research Campaign (MJH). 相似文献
48.
Pujana MA Han JD Starita LM Stevens KN Tewari M Ahn JS Rennert G Moreno V Kirchhoff T Gold B Assmann V Elshamy WM Rual JF Levine D Rozek LS Gelman RS Gunsalus KC Greenberg RA Sobhian B Bertin N Venkatesan K Ayivi-Guedehoussou N Solé X Hernández P Lázaro C Nathanson KL Weber BL Cusick ME Hill DE Offit K Livingston DM Gruber SB Parvin JD Vidal M 《Nature genetics》2007,39(11):1338-1349
Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic (or 'omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. This network shows higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer-associated gene BRCA1. Two case-control studies of incident breast cancer indicate that the HMMR locus is associated with higher risk of breast cancer in humans. Our network modeling strategy should be useful for the discovery of additional cancer-associated genes. 相似文献
49.
Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes 总被引:3,自引:0,他引:3
Kantarci S Al-Gazali L Hill RS Donnai D Black GC Bieth E Chassaing N Lacombe D Devriendt K Teebi A Loscertales M Robson C Liu T MacLaughlin DT Noonan KM Russell MK Walsh CA Donahoe PK Pober BR 《Nature genetics》2007,39(8):957-959
Donnai-Barrow syndrome is associated with agenesis of the corpus callosum, congenital diaphragmatic hernia, facial dysmorphology, ocular anomalies, sensorineural hearing loss and developmental delay. By studying multiplex families, we mapped this disorder to chromosome 2q23.3-31.1 and identified LRP2 mutations in six families with Donnai-Barrow syndrome and one family with facio-oculo-acoustico-renal syndrome. LRP2 encodes megalin, a multiligand uptake receptor that regulates levels of diverse circulating compounds. This work implicates a pathway with potential pharmacological therapeutic targets. 相似文献
50.
Thye T Owusu-Dabo E Vannberg FO van Crevel R Curtis J Sahiratmadja E Balabanova Y Ehmen C Muntau B Ruge G Sievertsen J Gyapong J Nikolayevskyy V Hill PC Sirugo G Drobniewski F van de Vosse E Newport M Alisjahbana B Nejentsev S Ottenhoff TH Hill AV Horstmann RD Meyer CG 《Nature genetics》2012,44(3):257-259
After imputation of data from the 1000 Genomes Project into a genome-wide dataset of Ghanaian individuals with tuberculosis and controls, we identified a resistance locus on chromosome 11p13 downstream of the WT1 gene (encoding Wilms tumor 1). The strongest signal was obtained at the rs2057178 SNP (P = 2.63 × 10(-9)). Replication in Gambian, Indonesian and Russian tuberculosis case-control study cohorts increased the significance level for the association with this SNP to P = 2.57 × 10(-11). 相似文献