排序方式: 共有87条查询结果,搜索用时 15 毫秒
61.
Consortium for Influenza Study at Shanghai Shanghai-MOST Key Laboratory for Disease Heal... 《科学通报(英文版)》2009,(13)
The outbreak of a novel influenza A(H1N1) virus across the globe poses a threat to human health.It is of paramount importance to develop a rapid,reliable and inexpensive diagnostic procedure.Based on the bioinformatic information from public database,primers specific for influenza A virus surface protein haemagglutinin(HA) of several subtypes(including H1,H2,H3,H5,H7 and H9) were designed.Primer-specific PCR products were subjected to sequencing for accurately distinguishing H1 and H3 subtypes from others.T... 相似文献
62.
GoDARTS UKPDS Diabetes Pharmacogenetics Study Group;Wellcome Trust Case Control Consortium Zhou K Bellenguez C Spencer CC Bennett AJ Coleman RL Tavendale R Hawley SA Donnelly LA Schofield C Groves CJ Burch L Carr F Strange A Freeman C Blackwell JM Bramon E Brown MA Casas JP Corvin A Craddock N Deloukas P Dronov S Duncanson A Edkins S Gray E Hunt S Jankowski J Langford C Markus HS Mathew CG Plomin R Rautanen A Sawcer SJ Samani NJ Trembath R Viswanathan AC Wood NW;MAGIC investigators 《Nature genetics》2011,43(2):117-120
Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 × 10(-9), odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. 相似文献
63.
EL Heinzen KJ Swoboda Y Hitomi F Gurrieri S Nicole B de Vries FD Tiziano B Fontaine NM Walley S Heavin E Panagiotakaki;European Alternating Hemiplegia of Childhood 《Nature genetics》2012,44(9):1030-1034
Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation in a case of familial AHC. Notably, most AHC cases are caused by one of seven recurrent ATP1A3 mutations, one of which was observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3. 相似文献
64.
Stahl EA Wegmann D Trynka G Gutierrez-Achury J Do R Voight BF Kraft P Chen R Kallberg HJ Kurreeman FA;Diabetes Genetics Replication Meta-analysis Consortium;Myocardial Infarction Genetics Consortium Kathiresan S Wijmenga C Gregersen PK Alfredsson L Siminovitch KA Worthington J de Bakker PI Raychaudhuri S Plenge RM 《Nature genetics》2012,44(5):483-489
The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases. 相似文献
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66.
Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium Strange A Capon F Spencer CC Knight J Weale ME Allen MH Barton A Band G Bellenguez C Bergboer JG Blackwell JM Bramon E Bumpstead SJ Casas JP Cork MJ Corvin A Deloukas P Dilthey A Duncanson A Edkins S Estivill X Fitzgerald O Freeman C Giardina E Gray E Hofer A Hüffmeier U Hunt SE Irvine AD Jankowski J Kirby B Langford C Lascorz J Leman J Leslie S Mallbris L Markus HS Mathew CG McLean WH McManus R 《Nature genetics》2010,42(11):985-990
To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10?? and two loci with a combined P < 5 × 10??). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10??). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis. 相似文献
67.
Evans DM Spencer CC Pointon JJ Su Z Harvey D Kochan G Oppermann U Opperman U Dilthey A Pirinen M Stone MA Appleton L Moutsianas L Moutsianis L Leslie S Wordsworth T Kenna TJ Karaderi T Thomas GP Ward MM Weisman MH Farrar C Bradbury LA Danoy P Inman RD Maksymowych W Gladman D Rahman P;Spondyloarthritis Research Consortium of Canada 《Nature genetics》2011,43(8):761-767
Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides. 相似文献
68.
Albagha OM Wani SE Visconti MR Alonso N Goodman K Brandi ML Cundy T Chung PY Dargie R Devogelaer JP Falchetti A Fraser WD Gennari L Gianfrancesco F Hooper MJ Van Hul W Isaia G Nicholson GC Nuti R Papapoulos S Montes Jdel P Ratajczak T Rea SL Rendina D Gonzalez-Sarmiento R Di Stefano M Ward LC Walsh JP Ralston SH;Genetic Determinants of Paget's Disease 《Nature genetics》2011,43(7):685-689
Paget's disease of bone (PDB) is a common disorder characterized by focal abnormalities of bone remodeling. We previously identified variants at the CSF1, OPTN and TNFRSF11A loci as risk factors for PDB by genome-wide association study. Here we extended this study, identified three new loci and confirmed their association with PDB in 2,215 affected individuals (cases) and 4,370 controls from seven independent populations. The new associations were with rs5742915 within PML on 15q24 (odds ratio (OR) = 1.34, P = 1.6 × 10(-14)), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 × 10(-11)) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 × 10(-10)). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 × 10(-17)) with PDB. These seven loci explained ~13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB. 相似文献
69.
International Consortium for Systemic Lupus Erythematosus Genetics 《Nature genetics》2008,40(2):204-210
Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE. 相似文献
70.
STAR Consortium Saar K Beck A Bihoreau MT Birney E Brocklebank D Chen Y Cuppen E Demonchy S Dopazo J Flicek P Foglio M Fujiyama A Gut IG Gauguier D Guigo R Guryev V Heinig M Hummel O Jahn N Klages S Kren V Kube M Kuhl H Kuramoto T Kuroki Y Lechner D Lee YA Lopez-Bigas N Lathrop GM Mashimo T Medina I Mott R Patone G Perrier-Cornet JA Platzer M Pravenec M Reinhardt R Sakaki Y Schilhabel M Schulz H Serikawa T Shikhagaie M Tatsumoto S Taudien S Toyoda A Voigt B Zelenika D Zimdahl H Hubner N 《Nature genetics》2008,40(5):560-566
The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a survey of genetic variation based on almost 3 million newly identified SNPs. We obtained accurate and complete genotypes for a subset of 20,238 SNPs across 167 distinct inbred rat strains, two rat recombinant inbred panels and an F2 intercross. Using 81% of these SNPs, we constructed high-density genetic maps, creating a large dataset of fully characterized SNPs for disease gene mapping. Our data characterize the population structure and illustrate the degree of linkage disequilibrium. We provide a detailed SNP map and demonstrate its utility for mapping of quantitative trait loci. This community resource is openly available and augments the genetic tools for this workhorse of physiological studies. 相似文献