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排序方式: 共有10000条查询结果,搜索用时 256 毫秒
871.
872.
Hahn CN Chong CE Carmichael CL Wilkins EJ Brautigan PJ Li XC Babic M Lin M Carmagnac A Lee YK Kok CH Gagliardi L Friend KL Ekert PG Butcher CM Brown AL Lewis ID To LB Timms AE Storek J Moore S Altree M Escher R Bardy PG Suthers GK D'Andrea RJ Horwitz MS Scott HS 《Nature genetics》2011,43(10):1012-1017
873.
874.
Crossan GP van der Weyden L Rosado IV Langevin F Gaillard PH McIntyre RE;Sanger Mouse Genetics Project Gallagher F Kettunen MI Lewis DY Brindle K Arends MJ Adams DJ Patel KJ 《Nature genetics》2011,43(2):147-152
The evolutionarily conserved SLX4 protein, a key regulator of nucleases, is critical for DNA damage response. SLX4 nuclease complexes mediate repair during replication and can also resolve Holliday junctions formed during homologous recombination. Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness Fanconi anemia. Btbd12-deficient animals are born at sub-Mendelian ratios, have greatly reduced fertility, are developmentally compromised and are prone to blood cytopenias. Btbd12(-/-) cells prematurely senesce, spontaneously accumulate damaged chromosomes and are particularly sensitive to DNA crosslinking agents. Genetic complementation reveals a crucial requirement for Btbd12 (also known as Slx4) to interact with the structure-specific endonuclease Xpf-Ercc1 to promote crosslink repair. The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway. 相似文献
875.
Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease 总被引:1,自引:0,他引:1
Naj AC Jun G Beecham GW Wang LS Vardarajan BN Buros J Gallins PJ Buxbaum JD Jarvik GP Crane PK Larson EB Bird TD Boeve BF Graff-Radford NR De Jager PL Evans D Schneider JA Carrasquillo MM Ertekin-Taner N Younkin SG Cruchaga C Kauwe JS Nowotny P Kramer P Hardy J Huentelman MJ Myers AJ Barmada MM Demirci FY Baldwin CT Green RC Rogaeva E St George-Hyslop P Arnold SE Barber R Beach T Bigio EH Bowen JD Boxer A Burke JR Cairns NJ Carlson CS Carney RM Carroll SL Chui HC Clark DG Corneveaux J Cotman CW 《Nature genetics》2011,43(5):436-441
The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility. 相似文献
876.
Genome-wide association study of leaf architecture in the maize nested association mapping population 总被引:13,自引:0,他引:13
Tian F Bradbury PJ Brown PJ Hung H Sun Q Flint-Garcia S Rocheford TR McMullen MD Holland JB Buckler ES 《Nature genetics》2011,43(2):159-162
US maize yield has increased eight-fold in the past 80 years, with half of the gain attributed to selection by breeders. During this time, changes in maize leaf angle and size have altered plant architecture, allowing more efficient light capture as planting density has increased. Through a genome-wide association study (GWAS) of the maize nested association mapping panel, we determined the genetic basis of important leaf architecture traits and identified some of the key genes. Overall, we demonstrate that the genetic architecture of the leaf traits is dominated by small effects, with little epistasis, environmental interaction or pleiotropy. In particular, GWAS results show that variations at the liguleless genes have contributed to more upright leaves. These results demonstrate that the use of GWAS with specially designed mapping populations is effective in uncovering the basis of key agronomic traits. 相似文献
877.
van de Laar IM Oldenburg RA Pals G Roos-Hesselink JW de Graaf BM Verhagen JM Hoedemaekers YM Willemsen R Severijnen LA Venselaar H Vriend G Pattynama PM Collée M Majoor-Krakauer D Poldermans D Frohn-Mulder IM Micha D Timmermans J Hilhorst-Hofstee Y Bierma-Zeinstra SM Willems PJ Kros JM Oei EH Oostra BA Wessels MW Bertoli-Avella AM 《Nature genetics》2011,43(2):121-126
Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis. 相似文献
878.
Schramek D Kotsinas A Meixner A Wada T Elling U Pospisilik JA Neely GG Zwick RH Sigl V Forni G Serrano M Gorgoulis VG Penninger JM 《Nature genetics》2011,43(3):212-219
Most preneoplastic lesions are quiescent and do not progress to form overt tumors. It has been proposed that oncogenic stress activates the DNA damage response and the key tumor suppressor p53, which prohibits tumor growth. However, the molecular pathways by which cells sense a premalignant state in vivo are largely unknown. Here we report that tissue-specific inactivation of the stress signaling kinase MKK7 in KRas(G12D)-driven lung carcinomas and NeuT-driven mammary tumors markedly accelerates tumor onset and reduces overall survival. Mechanistically, MKK7 acts through the kinases JNK1 and JNK2, and this signaling pathway directly couples oncogenic and genotoxic stress to the stability of p53, which is required for cell cycle arrest and suppression of epithelial cancers. These results show that MKK7 functions as a major tumor suppressor in lung and mammary cancer in mouse and identify MKK7 as a vital molecular sensor to set a cellular anti-cancer barrier. 相似文献
879.
Giardine B Borg J Higgs DR Peterson KR Philipsen S Maglott D Singleton BK Anstee DJ Basak AN Clark B Costa FC Faustino P Fedosyuk H Felice AE Francina A Galanello R Gallivan MV Georgitsi M Gibbons RJ Giordano PC Harteveld CL Hoyer JD Jarvis M Joly P Kanavakis E Kollia P Menzel S Miller W Moradkhani K Old J Papachatzopoulou A Papadakis MN Papadopoulos P Pavlovic S Perseu L Radmilovic M Riemer C Satta S Schrijver I Stojiljkovic M Thein SL Traeger-Synodinos J Tully R Wada T Waye JS Wiemann C 《Nature genetics》2011,43(4):295-301
We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases. 相似文献
880.
Burdon KP Macgregor S Hewitt AW Sharma S Chidlow G Mills RA Danoy P Casson R Viswanathan AC Liu JZ Landers J Henders AK Wood J Souzeau E Crawford A Leo P Wang JJ Rochtchina E Nyholt DR Martin NG Montgomery GW Mitchell P Brown MA Mackey DA Craig JE 《Nature genetics》2011,43(6):574-578
We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. 相似文献