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Genomewide scan and fine-mapping linkage studies in four European samples with bipolar affective disorder suggest a new susceptibility locus on chromosome 1p35-p36 and provides further evidence of loci on chromosome 4q31 and 6q24 总被引:2,自引:1,他引:1 下载免费PDF全文
Schumacher J Kaneva R Jamra RA Diaz GO Ohlraun S Milanova V Lee YA Rivas F Mayoral F Fuerst R Flaquer A Windemuth C Gay E Sanz S González MJ Gil S Cabaleiro F del Rio F Perez F Haro J Kostov C Chorbov V Nikolova-Hill A Stoyanova V Onchev G Kremensky I Strauch K Schulze TG Nürnberg P Gaebel W Klimke A Auburger G Wienker TF Kalaydjieva L Propping P Cichon S Jablensky A Rietschel M Nöthen MM 《American journal of human genetics》2005,77(6):1102-1111
We present the findings of a large linkage study of bipolar affective disorder (BPAD) that involved genomewide analysis of 52 families (448 genotyped individuals) of Spanish, Romany, and Bulgarian descent and further fine mapping of the 1p34-p36, 4q28-q31, and 6q15-q24 regions. An additional sample of 56 German families (280 individuals) was included for this fine-mapping step. The highest nonparametric linkage scores obtained in the fine mapping were 5.49 for 4q31 and 4.87 for 6q24 in the Romany families and 3.97 for 1p35-p36 in the Spanish sample. MOD-score (LOD scores maximized over genetic model parameters) analysis provided significant evidence of linkage to 4q31 and at least borderline significance for the 1p and 6q regions. On the basis of these results and previous positive research findings, 4q31 and 6q24 should now be considered confirmed BPAD susceptibility loci, and 1p35-p36 is proposed as a new putative locus that requires confirmation in replication studies. 相似文献
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Induction of apoptosis by rewiring the signal transduction of Epstein-Barr virus oncoprotein LMP1 toward caspase activation 总被引:1,自引:0,他引:1
The Epstein-Barr virus latent membrane protein 1 (LMP1) is an oncoprotein which mimics activated tumor necrosis factor receptor family members. Here we demonstrate the principle that an inducible association of the LMP1 cytoplasmic carboxyl terminus with caspase-8 by a heterodimerizing agent causes apoptosis. This process depends on the catalytic activity of caspase-8 and the ability of LMP1 to oligomerize constitutively at the plasma membrane. Our data indicate that chemical inducers of the association of the LMP1 carboxyl terminus with caspase-8 can kill LMP1-expressing cells selectively. Such compounds could be used as chemotherapeutic agents for LMP1-associated malignancies. 相似文献