排序方式: 共有53条查询结果,搜索用时 15 毫秒
31.
Stuart PE Nair RP Ellinghaus E Ding J Tejasvi T Gudjonsson JE Li Y Weidinger S Eberlein B Gieger C Wichmann HE Kunz M Ike R Krueger GG Bowcock AM Mrowietz U Lim HW Voorhees JJ Abecasis GR Weichenthal M Franke A Rahman P Gladman DD Elder JT 《Nature genetics》2010,42(11):1000-1004
We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10?11), one at FBXL19 (rs10782001, combined P = 9 × 10?1?) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10??). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10??; rs10782001, combined P = 4 × 10??; and rs12586317, combined P = 6 × 1??) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10??; rs10782001, combined P = 2 × 10??; and rs12586317, combined P = 1 × 10??). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10??). 相似文献
32.
Ramiro AR Jankovic M Callen E Difilippantonio S Chen HT McBride KM Eisenreich TR Chen J Dickins RA Lowe SW Nussenzweig A Nussenzweig MC 《Nature》2006,440(7080):105-109
Chromosomal translocations involving the immunoglobulin switch region are a hallmark feature of B-cell malignancies. However, little is known about the molecular mechanism by which primary B cells acquire or guard against these lesions. Here we find that translocations between c-myc and the IgH locus (Igh) are induced in primary B cells within hours of expression of the catalytically active form of activation-induced cytidine deaminase (AID), an enzyme that deaminates cytosine to produce uracil in DNA. Translocation also requires uracil DNA glycosylase (UNG), which removes uracil from DNA to create abasic sites that are then processed to double-strand breaks. The pathway that mediates aberrant joining of c-myc and Igh differs from intrachromosomal repair during immunoglobulin class switch recombination in that it does not require histone H2AX, p53 binding protein 1 (53BP1) or the non-homologous end-joining protein Ku80. In addition, translocations are inhibited by the tumour suppressors ATM, Nbs1, p19 (Arf) and p53, which is consistent with activation of DNA damage- and oncogenic stress-induced checkpoints during physiological class switching. Finally, we demonstrate that accumulation of AID-dependent, IgH-associated chromosomal lesions is not sufficient to enhance c-myc-Igh translocations. Our findings reveal a pathway for surveillance and protection against AID-dependent DNA damage, leading to chromosomal translocations. 相似文献
33.
Eva C. Schwarz Christina Backes Arne Knörck Nicole Ludwig Petra Leidinger Cora Hoxha Gertrud Schwär Thomas Grossmann Sabine C. Müller Martin Hart Jan Haas Valentina Galata Isabelle Müller Tobias Fehlmann Hermann Eichler Andre Franke Benjamin Meder Eckart Meese Markus Hoth Andreas Keller 《Cellular and molecular life sciences : CMLS》2016,73(16):3169-3181
34.
Lindblad-Toh K Garber M Zuk O Lin MF Parker BJ Washietl S Kheradpour P Ernst J Jordan G Mauceli E Ward LD Lowe CB Holloway AK Clamp M Gnerre S Alföldi J Beal K Chang J Clawson H Cuff J Di Palma F Fitzgerald S Flicek P Guttman M Hubisz MJ Jaffe DB Jungreis I Kent WJ Kostka D Lara M Martins AL Massingham T Moltke I Raney BJ Rasmussen MD Robinson J Stark A Vilella AJ Wen J Xie X Zody MC;Broad Institute Sequencing Platform Whole Genome Assembly Team Baldwin J Bloom T Chin CW Heiman D Nicol R 《Nature》2011,478(7370):476-482
The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ~4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ~60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease. 相似文献
35.
This paper uses multivariate time series models to specify the maritime steel traffic flow in the port of Antwerp. The time series considered are the total outgoing and total incoming maritime steel traffic and the total steel production in the EEC. The obtained time series models provide useful insight into the general behaviour of the maritime steel traffic flow during the period 1971–82. In particular, they provide a quantitative interpretation of important changes which took place in the European steel industry during that period. The multivariate time series models produce forecasts which are a substantial improvement over those obtained by univariate time series models. This is especially the case for the series of total incoming maritime steel traffic in the port of Antwerp, when differencing and transformation of the original data are applied. 相似文献
36.
Summary Larval brain mitotic karyotype ofAn. indefinitus from Kanchanaburi exhibits a supernumerary (B) chromosome which is apparently common in that population. 1 or 2 B-chromosomes have been observed in the samples from 5 isofemale lines examined.Acknowledgments. We thank K. Mongkolpanya and P. Kittayarak for species identification. Part of this work was supported by Mahidol University Research Fund and AFRIMS. 相似文献
37.
An i.v. injection of 548 microgram of killed Corynebacterium parvum into C57B1 mice leads to significant changes in serum lysozyme (muramidase) levels. After an initial fall at 24 h, the activity of the enzyme increased progressively, reached a peak on the 9th day and returned to control range after the 15th day. 相似文献
38.
Churchill GA Airey DC Allayee H Angel JM Attie AD Beatty J Beavis WD Belknap JK Bennett B Berrettini W Bleich A Bogue M Broman KW Buck KJ Buckler E Burmeister M Chesler EJ Cheverud JM Clapcote S Cook MN Cox RD Crabbe JC Crusio WE Darvasi A Deschepper CF Doerge RW Farber CR Forejt J Gaile D Garlow SJ Geiger H Gershenfeld H Gordon T Gu J Gu W de Haan G Hayes NL Heller C Himmelbauer H Hitzemann R Hunter K Hsu HC Iraqi FA Ivandic B Jacob HJ Jansen RC Jepsen KJ Johnson DK Johnson TE Kempermann G 《Nature genetics》2004,36(11):1133-1137
The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease. 相似文献
39.
ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating 总被引:17,自引:0,他引:17
Bienengraeber M Olson TM Selivanov VA Kathmann EC O'Cochlain F Gao F Karger AB Ballew JD Hodgson DM Zingman LV Pang YP Alekseev AE Terzic A 《Nature genetics》2004,36(4):382-387
Stress tolerance of the heart requires high-fidelity metabolic sensing by ATP-sensitive potassium (K(ATP)) channels that adjust membrane potential-dependent functions to match cellular energetic demand. Scanning of genomic DNA from individuals with heart failure and rhythm disturbances due to idiopathic dilated cardiomyopathy identified two mutations in ABCC9, which encodes the regulatory SUR2A subunit of the cardiac K(ATP) channel. These missense and frameshift mutations mapped to evolutionarily conserved domains adjacent to the catalytic ATPase pocket within SUR2A. Mutant SUR2A proteins showed aberrant redistribution of conformations in the intrinsic ATP hydrolytic cycle, translating into abnormal K(ATP) channel phenotypes with compromised metabolic signal decoding. Defective catalysis-mediated pore regulation is thus a mechanism for channel dysfunction and susceptibility to dilated cardiomyopathy. 相似文献
40.
G. Eliopoulos S. Andre N. P. Anagnou J. Meletis B. Halpern 《Cellular and molecular life sciences : CMLS》1979,35(7):908-909
Summary An i.v. injection of 548 g of killedCorynebacterium parvum into C57B1 mice leads to significant changes in serum lysozyme (muramidase) levels. After an initial fall at 24 h, the activity of the enzyme increased progressively, reached a peak on the 9th day and returned to control range after the 15th day. 相似文献