排序方式: 共有283条查询结果,搜索用时 31 毫秒
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Lausch E Janecke A Bros M Trojandt S Alanay Y De Laet C Hübner CA Meinecke P Nishimura G Matsuo M Hirano Y Tenoutasse S Kiss A Rosa RF Unger SL Renella R Bonafé L Spranger J Unger S Zabel B Superti-Furga A 《Nature genetics》2011,43(2):132-137
Vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases are the hallmarks of the genetic disorder spondyloenchondrodysplasia. We mapped a locus in five consanguineous families to chromosome 19p13 and identified mutations in ACP5, which encodes tartrate-resistant phosphatase (TRAP), in 14 affected individuals and showed that these mutations abolish enzyme function in the serum and cells of affected individuals. Phosphorylated osteopontin, a protein involved in bone reabsorption and in immune regulation, accumulates in serum, urine and cells cultured from TRAP-deficient individuals. Case-derived dendritic cells exhibit an altered cytokine profile and are more potent than matched control cells in stimulating allogeneic T cell proliferation in mixed lymphocyte reactions. These findings shed new light on the role of osteopontin and its regulation by TRAP in the pathogenesis of common autoimmune disorders. 相似文献
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Melum E Franke A Schramm C Weismüller TJ Gotthardt DN Offner FA Juran BD Laerdahl JK Labi V Björnsson E Weersma RK Henckaerts L Teufel A Rust C Ellinghaus E Balschun T Boberg KM Ellinghaus D Bergquist A Sauer P Ryu E Hov JR Wedemeyer J Lindkvist B Wittig M Porte RJ Holm K Gieger C Wichmann HE Stokkers P Ponsioen CY Runz H Stiehl A Wijmenga C Sterneck M Vermeire S Beuers U Villunger A Schrumpf E Lazaridis KN Manns MP Schreiber S Karlsen TH 《Nature genetics》2011,43(1):17-19
Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10?1? and P = 4.1 × 10??, respectively). 相似文献
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Rosendahl J Witt H Szmola R Bhatia E Ozsvári B Landt O Schulz HU Gress TM Pfützer R Löhr M Kovacs P Blüher M Stumvoll M Choudhuri G Hegyi P te Morsche RH Drenth JP Truninger K Macek M Puhl G Witt U Schmidt H Büning C Ockenga J Kage A Groneberg DA Nickel R Berg T Wiedenmann B Bödeker H Keim V Mössner J Teich N Sahin-Tóth M 《Nature genetics》2008,40(1):78-82
Chronic pancreatitis is a persistent inflammatory disease of the pancreas, in which the digestive protease trypsin has a fundamental pathogenetic role. Here we have analyzed the gene encoding the trypsin-degrading enzyme chymotrypsin C (CTRC) in German subjects with idiopathic or hereditary chronic pancreatitis. Two alterations in this gene, p.R254W and p.K247_R254del, were significantly overrepresented in the pancreatitis group, being present in 30 of 901 (3.3%) affected individuals but only 21 of 2,804 (0.7%) controls (odds ratio (OR) = 4.6; confidence interval (CI) = 2.6-8.0; P = 1.3 x 10(-7)). A replication study identified these two variants in 10 of 348 (2.9%) individuals with alcoholic chronic pancreatitis but only 3 of 432 (0.7%) subjects with alcoholic liver disease (OR = 4.2; CI = 1.2-15.5; P = 0.02). CTRC variants were also found in 10 of 71 (14.1%) Indian subjects with tropical pancreatitis but only 1 of 84 (1.2%) healthy controls (OR = 13.6; CI = 1.7-109.2; P = 0.0028). Functional analysis of the CTRC variants showed impaired activity and/or reduced secretion. The results indicate that loss-of-function alterations in CTRC predispose to pancreatitis by diminishing its protective trypsin-degrading activity. 相似文献
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Kozyrev SV Abelson AK Wojcik J Zaghlool A Linga Reddy MP Sanchez E Gunnarsson I Svenungsson E Sturfelt G Jönsen A Truedsson L Pons-Estel BA Witte T D'Alfonso S Barrizzone N Danieli MG Gutierrez C Suarez A Junker P Laustrup H Francisca González-Escribano M Martin J Abderrahim H Alarcón-Riquelme ME 《Nature genetics》2008,40(4):484
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Trabesinger A 《Nature》2005,435(7046):1173-1174
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WUSCHEL controls meristem function by direct regulation of cytokinin-inducible response regulators 总被引:2,自引:0,他引:2
Leibfried A To JP Busch W Stehling S Kehle A Demar M Kieber JJ Lohmann JU 《Nature》2005,438(7071):1172-1175
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Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin 总被引:14,自引:0,他引:14
Otto EA Loeys B Khanna H Hellemans J Sudbrak R Fan S Muerb U O'Toole JF Helou J Attanasio M Utsch B Sayer JA Lillo C Jimeno D Coucke P De Paepe A Reinhardt R Klages S Tsuda M Kawakami I Kusakabe T Omran H Imm A Tippens M Raymond PA Hill J Beales P He S Kispert A Margolis B Williams DS Swaroop A Hildebrandt F 《Nature genetics》2005,37(3):282-288
Nephronophthisis (NPHP) is the most frequent genetic cause of chronic renal failure in children. Identification of four genes mutated in NPHP subtypes 1-4 (refs. 4-9) has linked the pathogenesis of NPHP to ciliary functions. Ten percent of affected individuals have retinitis pigmentosa, constituting the renal-retinal Senior-Loken syndrome (SLSN). Here we identify, by positional cloning, mutations in an evolutionarily conserved gene, IQCB1 (also called NPHP5), as the most frequent cause of SLSN. IQCB1 encodes an IQ-domain protein, nephrocystin-5. All individuals with IQCB1 mutations have retinitis pigmentosa. Hence, we examined the interaction of nephrocystin-5 with RPGR (retinitis pigmentosa GTPase regulator), which is expressed in photoreceptor cilia and associated with 10-20% of retinitis pigmentosa. We show that nephrocystin-5, RPGR and calmodulin can be coimmunoprecipitated from retinal extracts, and that these proteins localize to connecting cilia of photoreceptors and to primary cilia of renal epithelial cells. Our studies emphasize the central role of ciliary dysfunction in the pathogenesis of SLSN. 相似文献