排序方式: 共有63条查询结果,搜索用时 31 毫秒
51.
BA Peters BG Kermani AB Sparks O Alferov P Hong A Alexeev Y Jiang F Dahl YT Tang J Haas K Robasky AW Zaranek JH Lee MP Ball JE Peterson H Perazich G Yeung J Liu L Chen MI Kennemer K Pothuraju K Konvicka M Tsoupko-Sitnikov KP Pant JC Ebert GB Nilsen J Baccash AL Halpern GM Church R Drmanac 《Nature》2012,487(7406):190-195
Recent advances in whole-genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, long fragment read (LFR) technology, which is similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100?picograms of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants were assembled into long haplotype contigs. Removal of false positive single nucleotide variants not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10?megabases. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications. 相似文献
52.
Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster 总被引:28,自引:0,他引:28
Dews M Homayouni A Yu D Murphy D Sevignani C Wentzel E Furth EE Lee WM Enders GH Mendell JT Thomas-Tikhonenko A 《Nature genetics》2006,38(9):1060-1065
Human adenocarcinomas commonly harbor mutations in the KRAS and MYC proto-oncogenes and the TP53 tumor suppressor gene. All three genetic lesions are potentially pro-angiogenic, as they sustain production of vascular endothelial growth factor (VEGF). Yet Kras-transformed mouse colonocytes lacking p53 formed indolent, poorly vascularized tumors, whereas additional transduction with a Myc-encoding retrovirus promoted vigorous vascularization and growth. In addition, VEGF levels were unaffected by Myc, but enhanced neovascularization correlated with downregulation of anti-angiogenic thrombospondin-1 (Tsp1) and related proteins, such as connective tissue growth factor (CTGF). Both Tsp1 and CTGF are predicted targets for repression by the miR-17-92 microRNA cluster, which was upregulated in colonocytes coexpressing K-Ras and c-Myc. Indeed, miR-17-92 knockdown with antisense 2'-O-methyl oligoribonucleotides partly restored Tsp1 and CTGF expression; in addition, transduction of Ras-only cells with a miR-17-92-encoding retrovirus reduced Tsp1 and CTGF levels. Notably, miR-17-92-transduced cells formed larger, better-perfused tumors. These findings establish a role for microRNAs in non-cell-autonomous Myc-induced tumor phenotypes. 相似文献
53.
Gudmundsson J Sulem P Manolescu A Amundadottir LT Gudbjartsson D Helgason A Rafnar T Bergthorsson JT Agnarsson BA Baker A Sigurdsson A Benediktsdottir KR Jakobsdottir M Xu J Blondal T Kostic J Sun J Ghosh S Stacey SN Mouy M Saemundsdottir J Backman VM Kristjansson K Tres A Partin AW Albers-Akkers MT Godino-Ivan Marcos J Walsh PC Swinkels DW Navarrete S Isaacs SD Aben KK Graif T Cashy J Ruiz-Echarri M Wiley KE Suarez BK Witjes JA Frigge M Ober C Jonsson E Einarsson GV Mayordomo JI Kiemeney LA 《Nature genetics》2007,39(5):631-637
Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (approximately 42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis. 相似文献
54.
Cyclostome bryozoans are relatively uncommon in intertidal habitats, where they are subordinate to cheilostomes and ctenostomes. Those that do occur tend to have small colonies that are relatively weakly calcified. Here we describe two new species of intertidal cyclostomes from Akkeshi Bay in northern Japan that are unusual in having large, heavily calcified colonies. One of these – Favosipora ainui sp. nov. – is the first species of this genus recorded from Japan. The second species – Disporella ezoensis sp. nov. – although belonging to a genus well known from Japan and elsewhere globally, is unusual for Disporella in possessing colonies that are vivid red in colour.http://zoobank.org/urn:lsid:zoobank.org:pub:995903E6-9C07-436A-B788-29BDE2FD5A88 相似文献
55.
Gudmundsson J Sulem P Rafnar T Bergthorsson JT Manolescu A Gudbjartsson D Agnarsson BA Sigurdsson A Benediktsdottir KR Blondal T Jakobsdottir M Stacey SN Kostic J Kristinsson KT Birgisdottir B Ghosh S Magnusdottir DN Thorlacius S Thorleifsson G Zheng SL Sun J Chang BL Elmore JB Breyer JP McReynolds KM Bradley KM Yaspan BL Wiklund F Stattin P Lindström S Adami HO McDonnell SK Schaid DJ Cunningham JM Wang L Cerhan JR St Sauver JL Isaacs SD Wiley KE Partin AW Walsh PC Polo S Ruiz-Echarri M 《Nature genetics》2008,40(3):281-283
We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and rs721048 on 2p15 (odds ratios (OR) = 1.23 and 1.15; P = 3.9 x 10(-13) and 7.7 x 10(-9), respectively). The 2p15 variant shows a significantly stronger association with more aggressive, rather than less aggressive, forms of the disease. 相似文献
56.
Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer
Stacey SN Manolescu A Sulem P Thorlacius S Gudjonsson SA Jonsson GF Jakobsdottir M Bergthorsson JT Gudmundsson J Aben KK Strobbe LJ Swinkels DW van Engelenburg KC Henderson BE Kolonel LN Le Marchand L Millastre E Andres R Saez B Lambea J Godino J Polo E Tres A Picelli S Rantala J Margolin S Jonsson T Sigurdsson H Jonsdottir T Hrafnkelsson J Johannsson J Sveinsson T Myrdal G Grimsson HN Sveinsdottir SG Alexiusdottir K Saemundsdottir J Sigurdsson A Kostic J Gudmundsson L Kristjansson K Masson G 《Nature genetics》2008,40(6):703-706
We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 x 10(-12) for rs10941679). The nearest gene, MRPS30, was previously implicated in apoptosis, ER-positive tumors and favorable prognosis. A recently reported signal in FGFR2 was also found to associate specifically with ER-positive breast cancer. 相似文献
57.
Helgadottir A Thorleifsson G Magnusson KP Grétarsdottir S Steinthorsdottir V Manolescu A Jones GT Rinkel GJ Blankensteijn JD Ronkainen A Jääskeläinen JE Kyo Y Lenk GM Sakalihasan N Kostulas K Gottsäter A Flex A Stefansson H Hansen T Andersen G Weinsheimer S Borch-Johnsen K Jorgensen T Shah SH Quyyumi AA Granger CB Reilly MP Austin H Levey AI Vaccarino V Palsdottir E Walters GB Jonsdottir T Snorradottir S Magnusdottir D Gudmundsson G Ferrell RE Sveinbjornsdottir S Hernesniemi J Niemelä M Limet R 《Nature genetics》2008,40(2):217-224
Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases. 相似文献
58.
Reconstructing the density fluctuations in the early Universe that evolved into the distribution of galaxies we see today is a challenge to modern cosmology. An accurate reconstruction would allow us to test cosmological models by simulating the evolution starting from the reconstructed primordial state and comparing it to observations. Several reconstruction techniques have been proposed, but they all suffer from lack of uniqueness because the velocities needed to produce a unique reconstruction usually are not known. Here we show that reconstruction can be reduced to a well-determined problem of optimization, and present a specific algorithm that provides excellent agreement when tested against data from N-body simulations. By applying our algorithm to the redshift surveys now under way, we will be able to recover reliably the properties of the primeval fluctuation field of the local Universe, and to determine accurately the peculiar velocities (deviations from the Hubble expansion) and the true positions of many more galaxies than is feasible by any other method. 相似文献
59.
Cossette P Liu L Brisebois K Dong H Lortie A Vanasse M Saint-Hilaire JM Carmant L Verner A Lu WY Wang YT Rouleau GA 《Nature genetics》2002,31(2):184-189
Although many genes that predispose for epilepsy in humans have been determined, those that underlie the classical syndromes of idiopathic generalized epilepsy (IGE) have yet to be identified. We report that an Ala322Asp mutation in GABRA1, encoding the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A (GABA(A)), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABA(A) receptors that contain the mutant subunit show a lesser amplitude of GABA-activated currents in vitro, indicating that seizures may result from loss of function of this inhibitory ligand-gated channel. Our results confirm that mutation of GABRA1 predisposes towards a common idiopathic generalized epilepsy syndrome in humans. 相似文献
60.
Butland G Peregrín-Alvarez JM Li J Yang W Yang X Canadien V Starostine A Richards D Beattie B Krogan N Davey M Parkinson J Greenblatt J Emili A 《Nature》2005,433(7025):531-537
Proteins often function as components of multi-subunit complexes. Despite its long history as a model organism, no large-scale analysis of protein complexes in Escherichia coli has yet been reported. To this end, we have targeted DNA cassettes into the E. coli chromosome to create carboxy-terminal, affinity-tagged alleles of 1,000 open reading frames (approximately 23% of the genome). A total of 857 proteins, including 198 of the most highly conserved, soluble non-ribosomal proteins essential in at least one bacterial species, were tagged successfully, whereas 648 could be purified to homogeneity and their interacting protein partners identified by mass spectrometry. An interaction network of protein complexes involved in diverse biological processes was uncovered and validated by sequential rounds of tagging and purification. This network includes many new interactions as well as interactions predicted based solely on genomic inference or limited phenotypic data. This study provides insight into the function of previously uncharacterized bacterial proteins and the overall topology of a microbial interaction network, the core components of which are broadly conserved across Prokaryota. 相似文献