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排序方式: 共有137条查询结果,搜索用时 15 毫秒
111.
Enciso-Mora V Broderick P Ma Y Jarrett RF Hjalgrim H Hemminki K van den Berg A Olver B Lloyd A Dobbins SE Lightfoot T van Leeuwen FE Försti A Diepstra A Broeks A Vijayakrishnan J Shield L Lake A Montgomery D Roman E Engert A von Strandmann EP Reiners KS Nolte IM Smedby KE Adami HO Russell NS Glimelius B Hamilton-Dutoit S de Bruin M Ryder LP Molin D Sorensen KM Chang ET Taylor M Cooke R Hofstra R Westers H van Wezel T van Eijk R Ashworth A Rostgaard K Melbye M Swerdlow AJ Houlston RS 《Nature genetics》2010,42(12):1126-1130
To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10(-8)), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10(-13)) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10(-8)). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10(-50)). These data provide new insight into the pathogenesis of cHL. 相似文献
112.
A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21 总被引:16,自引:0,他引:16
Tomlinson I Webb E Carvajal-Carmona L Broderick P Kemp Z Spain S Penegar S Chandler I Gorman M Wood W Barclay E Lubbe S Martin L Sellick G Jaeger E Hubner R Wild R Rowan A Fielding S Howarth K;CORGI Consortium Silver A Atkin W Muir K Logan R Kerr D Johnstone E Sieber O Gray R Thomas H Peto J Cazier JB Houlston R 《Nature genetics》2007,39(8):984-988
Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome-wide association study of 550,000 tag SNPs in 930 familial colorectal tumor cases and 960 controls. The most strongly associated SNP (P = 1.72 x 10(-7), allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected individuals and 3,752 controls; 1,901 affected individuals and 1,079 controls; 1,072 affected individuals and 415 controls) and replicated the association, providing P = 1.27 x 10(-14) (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16-1.39) and 1.47 (95% c.i.: 1.34-1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 individuals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10-1.34; P = 6.89 x 10(-5)). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia. 相似文献
113.
Richards A van den Maagdenberg AM Jen JC Kavanagh D Bertram P Spitzer D Liszewski MK Barilla-Labarca ML Terwindt GM Kasai Y McLellan M Grand MG Vanmolkot KR de Vries B Wan J Kane MJ Mamsa H Schäfer R Stam AH Haan J de Jong PT Storimans CW van Schooneveld MJ Oosterhuis JA Gschwendter A Dichgans M Kotschet KE Hodgkinson S Hardy TA Delatycki MB Hajj-Ali RA Kothari PH Nelson SF Frants RR Baloh RW Ferrari MD Atkinson JP 《Nature genetics》2007,39(9):1068-1070
Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias. 相似文献
114.
Geometry sensing by dendritic cells dictates spatial organization and PGE2-induced dissolution of podosomes 总被引:1,自引:1,他引:0
van den Dries K van Helden SF Riet Jt Diez-Ahedo R Manzo C Oud MM van Leeuwen FN Brock R Garcia-Parajo MF Cambi A Figdor CG 《Cellular and molecular life sciences : CMLS》2012,69(11):1889-1901
Assembly and disassembly of adhesion structures such as focal adhesions (FAs) and podosomes regulate cell adhesion and differentiation. On antigen-presenting dendritic cells (DCs), acquisition of a migratory and immunostimulatory phenotype depends on podosome dissolution by prostaglandin E(2) (PGE(2)). Whereas the effects of physico-chemical and topographical cues have been extensively studied on FAs, little is known about how podosomes respond to these signals. Here, we show that, unlike for FAs, podosome formation is not controlled by substrate physico-chemical properties. We demonstrate that cell adhesion is the only prerequisite for podosome formation and that substrate availability dictates podosome density. Interestingly, we show that DCs sense 3-dimensional (3-D) geometry by aligning podosomes along the edges of 3-D micropatterned surfaces. Finally, whereas on a 2-dimensional (2-D) surface PGE(2) causes a rapid increase in activated RhoA levels leading to fast podosome dissolution, 3-D geometric cues prevent PGE(2)-mediated RhoA activation resulting in impaired podosome dissolution even after prolonged stimulation. Our findings indicate that 2-D and 3-D geometric cues control the spatial organization of podosomes. More importantly, our studies demonstrate the importance of substrate dimensionality in regulating podosome dissolution and suggest that substrate dimensionality plays an important role in controlling DC activation, a key process in initiating immune responses. 相似文献
115.
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
116.
117.
118.
Lindström S Vachon CM Li J Varghese J Thompson D Warren R Brown J Leyland J Audley T Wareham NJ Loos RJ Paterson AD Rommens J Waggott D Martin LJ Scott CG Pankratz VS Hankinson SE Hazra A Hunter DJ Hopper JL Southey MC Chanock SJ Silva Idos S Liu J Eriksson L Couch FJ Stone J Apicella C Czene K Kraft P Hall P Easton DF Boyd NF Tamimi RM 《Nature genetics》2011,43(3):185-187
High-percent mammographic density adjusted for age and body mass index is one of the strongest risk factors for breast cancer. We conducted a meta analysis of five genome-wide association studies of percent mammographic density and report an association with rs10995190 in ZNF365 (combined P = 9.6 × 10(-10)). Common variants in ZNF365 have also recently been associated with susceptibility to breast cancer. 相似文献
119.
Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. 总被引:28,自引:0,他引:28
Sergey Kalachikov Oleg Evgrafov Barbara Ross Melodie Winawer Christie Barker-Cummings Filippo Martinelli Boneschi Chang Choi Pavel Morozov Kamna Das Elita Teplitskaya Andrew Yu Eftihia Cayanis Graciela Penchaszadeh Andreas H Kottmann Timothy A Pedley W Allen Hauser Ruth Ottman T Conrad Gilliam 《Nature genetics》2002,30(3):335-341
The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures. Here we describe identification of the causative gene in autosomal-dominant partial epilepsy with auditory features (ADPEAF, MIM 600512), a rare form of idiopathic lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. We constructed a complete, 4.2-Mb physical map across the genetically implicated disease-gene region, identified 28 putative genes (Fig. 1) and resequenced all or part of 21 genes before identifying presumptive mutations in one copy of the leucine-rich, glioma-inactivated 1 gene (LGI1) in each of five families with ADPEAF. Previous studies have indicated that loss of both copies of LGI1 promotes glial tumor progression. We show that the expression pattern of mouse Lgi1 is predominantly neuronal and is consistent with the anatomic regions involved in temporal lobe epilepsy. Discovery of LGI1 as a cause of ADPEAF suggests new avenues for research on pathogenic mechanisms of idiopathic epilepsies. 相似文献
120.
Types of cell contacts in arterial smooth muscle 总被引:1,自引:0,他引:1
Ruth M. Henderson 《Cellular and molecular life sciences : CMLS》1975,31(1):103-105
Zusammenfassung Nachweis, dass in Arteriolen sowie in präkapillaren Arteriolen des Hunde-Duodenums nur eine einfache Aneinanderlagerung der Muskelzellen erfolgt und keine gap junctions, wie sie in den Muskelschichten der Hohlwandorgane vorhanden sind. 相似文献