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排序方式: 共有192条查询结果,搜索用时 15 毫秒
161.
Hunt KA Zhernakova A Turner G Heap GA Franke L Bruinenberg M Romanos J Dinesen LC Ryan AW Panesar D Gwilliam R Takeuchi F McLaren WM Holmes GK Howdle PD Walters JR Sanders DS Playford RJ Trynka G Mulder CJ Mearin ML Verbeek WH Trimble V Stevens FM O'Morain C Kennedy NP Kelleher D Pennington DJ Strachan DP McArdle WL Mein CA Wapenaar MC Deloukas P McGinnis R McManus R Wijmenga C van Heel DA 《Nature genetics》2008,40(4):395-402
Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways. 相似文献
162.
Albers CA Paul DS Schulze H Freson K Stephens JC Smethurst PA Jolley JD Cvejic A Kostadima M Bertone P Breuning MH Debili N Deloukas P Favier R Fiedler J Hobbs CM Huang N Hurles ME Kiddle G Krapels I Nurden P Ruivenkamp CA Sambrook JG Smith K Stemple DL Strauss G Thys C van Geet C Newbury-Ecob R Ouwehand WH Ghevaert C 《Nature genetics》2012,44(4):435-9, S1-2
163.
Broderick P Chubb D Johnson DC Weinhold N Försti A Lloyd A Olver B Ma YP Dobbins SE Walker BA Davies FE Gregory WA Child JA Ross FM Jackson GH Neben K Jauch A Hoffmann P Mühleisen TW Nöthen MM Moebus S Tomlinson IP Goldschmidt H Hemminki K Morgan GJ Houlston RS 《Nature genetics》2012,44(1):58-61
To identify risk variants for multiple myeloma, we conducted a genome-wide association study of 1,675 individuals with multiple myeloma and 5,903 control subjects. We identified risk loci for multiple myeloma at 3p22.1 (rs1052501 in ULK4; odds ratio (OR) = 1.32; P = 7.47 × 10(-9)) and 7p15.3 (rs4487645, OR = 1.38; P = 3.33 × 10(-15)). In addition, we observed a promising association at 2p23.3 (rs6746082, OR = 1.29; P = 1.22 × 10(-7)). Our study identifies new genomic regions associated with multiple myeloma risk that may lead to new etiological insights. 相似文献
164.
Cox A Dunning AM Garcia-Closas M Balasubramanian S Reed MW Pooley KA Scollen S Baynes C Ponder BA Chanock S Lissowska J Brinton L Peplonska B Southey MC Hopper JL McCredie MR Giles GG Fletcher O Johnson N dos Santos Silva I Gibson L Bojesen SE Nordestgaard BG Axelsson CK Torres D Hamann U Justenhoven C Brauch H Chang-Claude J Kropp S Risch A Wang-Gohrke S Schürmann P Bogdanova N Dörk T Fagerholm R Aaltonen K Blomqvist C Nevanlinna H Seal S Renwick A Stratton MR Rahman N Sangrajrang S Hughes D 《Nature genetics》2007,39(3):352-358
The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies. 相似文献
165.
Ballif BC Hornor SA Jenkins E Madan-Khetarpal S Surti U Jackson KE Asamoah A Brock PL Gowans GC Conway RL Graham JM Medne L Zackai EH Shaikh TH Geoghegan J Selzer RR Eis PS Bejjani BA Shaffer LG 《Nature genetics》2007,39(9):1071-1073
We have identified a recurrent de novo pericentromeric deletion in 16p11.2-p12.2 in four individuals with developmental disabilities by microarray-based comparative genomic hybridization analysis. The identification of common clinical features in these four individuals along with the characterization of complex segmental duplications flanking the deletion regions suggests that nonallelic homologous recombination mediated these rearrangements and that deletions in 16p11.2-p12.2 constitute a previously undescribed syndrome. 相似文献
166.
167.
A naturally occurring epigenetic mutation in a gene encoding an SBP-box transcription factor inhibits tomato fruit ripening 总被引:26,自引:0,他引:26
Manning K Tör M Poole M Hong Y Thompson AJ King GJ Giovannoni JJ Seymour GB 《Nature genetics》2006,38(8):948-952
A major component in the regulatory network controlling fruit ripening is likely to be the gene at the tomato Colorless non-ripening (Cnr) locus. The Cnr mutation results in colorless fruits with a substantial loss of cell-to-cell adhesion. The nature of the mutation and the identity of the Cnr gene were previously unknown. Using positional cloning and virus-induced gene silencing, here we demonstrate that an SBP-box (SQUAMOSA promoter binding protein-like) gene resides at the Cnr locus. Furthermore, the Cnr phenotype results from a spontaneous epigenetic change in the SBP-box promoter. The discovery that Cnr is an epimutation was unexpected, as very few spontaneous epimutations have been described in plants. This study demonstrates that an SBP-box gene is critical for normal ripening and highlights the likely importance of epialleles in plant development and the generation of natural variation. 相似文献
168.
Rees MI Harvey K Pearce BR Chung SK Duguid IC Thomas P Beatty S Graham GE Armstrong L Shiang R Abbott KJ Zuberi SM Stephenson JB Owen MJ Tijssen MA van den Maagdenberg AM Smart TG Supplisson S Harvey RJ 《Nature genetics》2006,38(7):801-806
Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine receptor (GlyR) alpha1 subunit (GLRA1). Genetic heterogeneity has been confirmed in rare sporadic cases, with mutations affecting other postsynaptic glycinergic proteins including the GlyR beta subunit (GLRB), gephyrin (GPHN) and RhoGEF collybistin (ARHGEF9). However, many individuals diagnosed with sporadic hyperekplexia do not carry mutations in these genes. Here we show that missense, nonsense and frameshift mutations in SLC6A5 (ref. 8), encoding the presynaptic glycine transporter 2 (GlyT2), also cause hyperekplexia. Individuals with mutations in SLC6A5 present with hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. SLC6A5 mutations result in defective subcellular GlyT2 localization, decreased glycine uptake or both, with selected mutations affecting predicted glycine and Na+ binding sites. 相似文献
169.
Nugent PE Sullivan M Cenko SB Thomas RC Kasen D Howell DA Bersier D Bloom JS Kulkarni SR Kandrashoff MT Filippenko AV Silverman JM Marcy GW Howard AW Isaacson HT Maguire K Suzuki N Tarlton JE Pan YC Bildsten L Fulton BJ Parrent JT Sand D Podsiadlowski P Bianco FB Dilday B Graham ML Lyman J James P Kasliwal MM Law NM Quimby RM Hook IM Walker ES Mazzali P Pian E Ofek EO Gal-Yam A Poznanski D 《Nature》2011,480(7377):344-347
Type Ia supernovae have been used empirically as 'standard candles' to demonstrate the acceleration of the expansion of the Universe even though fundamental details, such as the nature of their progenitor systems and how the stars explode, remain a mystery. There is consensus that a white dwarf star explodes after accreting matter in a binary system, but the secondary body could be anything from a main-sequence star to a red giant, or even another white dwarf. This uncertainty stems from the fact that no recent type Ia supernova has been discovered close enough to Earth to detect the stars before explosion. Here we report early observations of supernova SN 2011fe in the galaxy M101 at a distance from Earth of 6.4 megaparsecs. We find that the exploding star was probably a carbon-oxygen white dwarf, and from the lack of an early shock we conclude that the companion was probably a main-sequence star. Early spectroscopy shows high-velocity oxygen that slows rapidly, on a timescale of hours, and extensive mixing of newly synthesized intermediate-mass elements in the outermost layers of the supernova. A companion paper uses pre-explosion images to rule out luminous red giants and most helium stars as companions to the progenitor. 相似文献
170.
Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. However, the mechanism for how these opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic metabolic requirements remains unclear. Here we show that the ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the rat brain tissue. When oxygen availability is lowered and astrocyte calcium concentration is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter-mediated uptake from the extracellular space of prostaglandin E(2), leading to accumulation and subsequent vasodilation. In conditions of low oxygen concentration extracellular adenosine also increases, which blocks astrocyte-mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation. 相似文献