排序方式: 共有17条查询结果,搜索用时 15 毫秒
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Rothberg JM Hinz W Rearick TM Schultz J Mileski W Davey M Leamon JH Johnson K Milgrew MJ Edwards M Hoon J Simons JF Marran D Myers JW Davidson JF Branting A Nobile JR Puc BP Light D Clark TA Huber M Branciforte JT Stoner IB Cawley SE Lyons M Fu Y Homer N Sedova M Miao X Reed B Sabina J Feierstein E Schorn M Alanjary M Dimalanta E Dressman D Kasinskas R Sokolsky T Fidanza JA Namsaraev E McKernan KJ Williams A Roth GT Bustillo J 《Nature》2011,475(7356):348-352
The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome. 相似文献
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Golubchik T Brueggemann AB Street T Gertz RE Spencer CC Ho T Giannoulatou E Link-Gelles R Harding RM Beall B Peto TE Moore MR Donnelly P Crook DW Bowden R 《Nature genetics》2012,44(3):352-355
Streptococcus pneumoniae ('pneumococcus') causes an estimated 14.5 million cases of serious disease and 826,000 deaths annually in children under 5 years of age(1). The highly effective introduction of the PCV7 pneumococcal vaccine in 2000 in the United States(2,3) provided an unprecedented opportunity to investigate the response of an important pathogen to widespread, vaccine-induced selective pressure. Here, we use array-based sequencing of 62 isolates from a US national monitoring program to study five independent instances of vaccine escape recombination(4), showing the simultaneous transfer of multiple and often large (up to at least 44 kb) DNA fragments. We show that one such new strain quickly became established, spreading from east to west across the United States. These observations clarify the roles of recombination and selection in the population genomics of pneumococcus and provide proof of principle of the considerable value of combining genomic and epidemiological information in the surveillance and enhanced understanding of infectious diseases. 相似文献
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S Neph J Vierstra AB Stergachis AP Reynolds E Haugen B Vernot RE Thurman S John R Sandstrom AK Johnson MT Maurano R Humbert E Rynes H Wang S Vong K Lee D Bates M Diegel V Roach D Dunn J Neri A Schafer RS Hansen T Kutyavin E Giste M Weaver T Canfield P Sabo M Zhang G Balasundaram R Byron MJ MacCoss JM Akey MA Bender M Groudine R Kaul JA Stamatoyannopoulos 《Nature》2012,489(7414):83-90
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Subtypes of medulloblastoma have distinct developmental origins 总被引:2,自引:0,他引:2
Gibson P Tong Y Robinson G Thompson MC Currle DS Eden C Kranenburg TA Hogg T Poppleton H Martin J Finkelstein D Pounds S Weiss A Patay Z Scoggins M Ogg R Pei Y Yang ZJ Brun S Lee Y Zindy F Lindsey JC Taketo MM Boop FA Sanford RA Gajjar A Clifford SC Roussel MF McKinnon PJ Gutmann DH Ellison DW Wechsler-Reya R Gilbertson RJ 《Nature》2010,468(7327):1095-1099
Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour. These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype). The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT subtype) arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumours infiltrate the dorsal brainstem, whereas SHH-subtype tumours are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1(+) precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence, to our knowledge, that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer. 相似文献
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Nijnik A Woodbine L Marchetti C Dawson S Lambe T Liu C Rodrigues NP Crockford TL Cabuy E Vindigni A Enver T Bell JI Slijepcevic P Goodnow CC Jeggo PA Cornall RJ 《Nature》2007,447(7145):686-690
Accumulation of DNA damage leading to adult stem cell exhaustion has been proposed to be a principal mechanism of ageing. Here we address this question by taking advantage of the highly specific role of DNA ligase IV in the repair of DNA double-strand breaks by non-homologous end-joining, and by the discovery of a unique mouse strain with a hypomorphic Lig4(Y288C) mutation. The Lig4(Y288C) mouse, identified by means of a mutagenesis screening programme, is a mouse model for human LIG4 syndrome, showing immunodeficiency and growth retardation. Diminished DNA double-strand break repair in the Lig4(Y288C) strain causes a progressive loss of haematopoietic stem cells and bone marrow cellularity during ageing, and severely impairs stem cell function in tissue culture and transplantation. The sensitivity of haematopoietic stem cells to non-homologous end-joining deficiency is therefore a key determinant of their ability to maintain themselves against physiological stress over time and to withstand culture and transplantation. 相似文献
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The accessible chromatin landscape of the human genome 总被引:2,自引:0,他引:2
RE Thurman E Rynes R Humbert J Vierstra MT Maurano E Haugen NC Sheffield AB Stergachis H Wang B Vernot K Garg S John R Sandstrom D Bates L Boatman TK Canfield M Diegel D Dunn AK Ebersol T Frum E Giste AK Johnson EM Johnson T Kutyavin B Lajoie BK Lee K Lee D London D Lotakis S Neph F Neri ED Nguyen H Qu AP Reynolds V Roach A Safi ME Sanchez A Sanyal A Shafer JM Simon L Song S Vong M Weaver Y Yan Z Zhang Z Zhang B Lenhard M Tewari MO Dorschner RS Hansen PA Navas G Stamatoyannopoulos VR Iyer 《Nature》2012,489(7414):75-82