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排序方式: 共有93条查询结果,搜索用时 318 毫秒
21.
Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility 总被引:1,自引:0,他引:1
Franke A Balschun T Karlsen TH Sventoraityte J Nikolaus S Mayr G Domingues FS Albrecht M Nothnagel M Ellinghaus D Sina C Onnie CM Weersma RK Stokkers PC Wijmenga C Gazouli M Strachan D McArdle WL Vermeire S Rutgeerts P Rosenstiel P Krawczak M Vatn MH;IBSEN study group Mathew CG Schreiber S 《Nature genetics》2008,40(11):1319-1323
Inflammatory bowel disease (IBD) typically manifests as either ulcerative colitis (UC) or Crohn's disease (CD). Systematic identification of susceptibility genes for IBD has thus far focused mainly on CD, and little is known about the genetic architecture of UC. Here we report a genome-wide association study with 440,794 SNPs genotyped in 1,167 individuals with UC and 777 healthy controls. Twenty of the most significantly associated SNPs were tested for replication in three independent European case-control panels comprising a total of 1,855 individuals with UC and 3,091 controls. Among the four consistently replicated markers, SNP rs3024505 immediately flanking the IL10 (interleukin 10) gene on chromosome 1q32.1 showed the most significant association in the combined verification samples (P = 1.35 x 10(-12); OR = 1.46 (1.31-1.62)). The other markers were located in ARPC2 and in the HLA-BTNL2 region. Association between rs3024505 and CD (1,848 cases, 1,804 controls) was weak (P = 0.013; OR = 1.17 (1.01-1.34)). IL10 is an immunosuppressive cytokine that has long been proposed to influence IBD pathophysiology. Our findings strongly suggest that defective IL10 function is central to the pathogenesis of the UC subtype of IBD. 相似文献
22.
Tomlinson IP Webb E Carvajal-Carmona L Broderick P Howarth K Pittman AM Spain S Lubbe S Walther A Sullivan K Jaeger E Fielding S Rowan A Vijayakrishnan J Domingo E Chandler I Kemp Z Qureshi M Farrington SM Tenesa A Prendergast JG Barnetson RA Penegar S Barclay E Wood W Martin L Gorman M Thomas H Peto J Bishop DT Gray R Maher ER Lucassen A Kerr D Evans DG;CORGI Consortium Schafmayer C Buch S Völzke H Hampe J Schreiber S John U Koessler T Pharoah P van Wezel T Morreau H Wijnen JT Hopper JL 《Nature genetics》2008,40(5):623-630
To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 x 10(-13) overall; P = 6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P = 3.3 x 10(-18) overall; P = 9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition. 相似文献
23.
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy 总被引:14,自引:0,他引:14
Pandit B Sarkozy A Pennacchio LA Carta C Oishi K Martinelli S Pogna EA Schackwitz W Ustaszewska A Landstrom A Bos JM Ommen SR Esposito G Lepri F Faul C Mundel P López Siguero JP Tenconi R Selicorni A Rossi C Mazzanti L Torrente I Marino B Digilio MC Zampino G Ackerman MJ Dallapiccola B Tartaglia M Gelb BD 《Nature genetics》2007,39(8):1007-1012
Noonan and LEOPARD syndromes are developmental disorders with overlapping features, including cardiac abnormalities, short stature and facial dysmorphia. Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases. Here, we report that 18 of 231 individuals with Noonan syndrome without known mutations (corresponding to 3% of all affected individuals) and two of six individuals with LEOPARD syndrome without PTPN11 mutations have missense mutations in RAF1, which encodes a serine-threonine kinase that activates MEK1 and MEK2. Most mutations altered a motif flanking Ser259, a residue critical for autoinhibition of RAF1 through 14-3-3 binding. Of 19 subjects with a RAF1 mutation in two hotspots, 18 (or 95%) showed hypertrophic cardiomyopathy (HCM), compared with the 18% prevalence of HCM among individuals with Noonan syndrome in general. Ectopically expressed RAF1 mutants from the two HCM hotspots had increased kinase activity and enhanced ERK activation, whereas non-HCM-associated mutants were kinase impaired. Our findings further implicate increased RAS signaling in pathological cardiomyocyte hypertrophy. 相似文献
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Zusammenfassung Die Rotationsdispersionskurven einiger optisch aktiver Dekalonderivate sind gemessen worden. Ihre Amplituden (a) und die Amplitudenbeiträge (a) der Substituenten werden im Rahmen der Oktantenregel diskutiert.
Paper V of the series Optical Rotatory Dispersion. For Paper IV seeC. Djerassi andW. Klyne, Proc. Nat. Acad. Sci. Washington, in press (1962). 相似文献
Paper V of the series Optical Rotatory Dispersion. For Paper IV seeC. Djerassi andW. Klyne, Proc. Nat. Acad. Sci. Washington, in press (1962). 相似文献
26.
Margaret Hitchcock M. Wendy Schneider 《Cellular and molecular life sciences : CMLS》1973,29(11):1369-1370
Zusammenfassung Es zeigt sich, dass die anaphylaktische Histaminausschüttung Calcium benötigt und bei neidriger Temperatur vollkommen gehemmt wird. Bei Zugabe der Substanz 48/80 erweist sich die dadurch hervorgerufene Histaminausschüttung als dosisabhängig und benötigt kein extrazelluläres Calcium. Die Reaktion wird bei niedriger Temperatur (4°C) nur teilweise gehemmt. Sie kann daher nicht als zweckmässiges Modell für das Studium der anaphylaktischen Histaminausschüttung der Lunge angesehen werden.
This investigation was supported by United States Public Health Service Grants Nos. OH-00304 and HE-14179. 相似文献
This investigation was supported by United States Public Health Service Grants Nos. OH-00304 and HE-14179. 相似文献
27.
Estimates are made of the number of potential marriage partners available for unmarried men and women, by age, in Great Britain in 1991 and how this varies across local districts. The preferences of men and women in relation to partner ages are taken into account in the estimates. Average partner supply declines by age for women and increases with age for men. Marriage markets differ between local areas but the differentiation is not as substantial as in many other aspects of local demography and is a good deal less than the variation that occurs through time. Young women and older men have advantageous marriage markets almost everywhere while young men and older women are at a disadvantage in almost all areas. 相似文献
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Constância M Hemberger M Hughes J Dean W Ferguson-Smith A Fundele R Stewart F Kelsey G Fowden A Sibley C Reik W 《Nature》2002,417(6892):945-948