Physical mapping and genomic structure of the human TNFR2 gene
ABSTRACT The tumor necrosis factor receptor 2 (TNFR2) gene localizes to 1p36. 2, a genomic region characteristically deleted in neuroblastomas and other malignancies. In addition, TNFR2 is the principal mediator of the effects of TNF on cellular immunity, and it may cooperate with TNFR1 in the killing of nonlymphoid cells. Therefore, we undertook an analysis of the genomic structure and precise physical mapping of this gene. The TNFR2 gene is contained on 10 exons that span 26 kb. Most of the functional domains of TNFR2 are encoded by separate exons, and each of the repeats of the extracellular cysteine-rich domain is interrupted by an intron. The genomic structure reveals a close relationship to TNFR1, another member of the TNFR superfamily. Based on electrophoretic analysis of yeast artificial chromosomes, TNFR2 maps within 400 kb of the genetic marker D1S434. In addition, we have identified a new polymorphic dinucleotide repeat within intron 4 of TNFR2. The genetic sequence information and exon-intron boundaries we have determined will facilitate mutational analysis of this gene to determine its potential role in neuroblastoma, as well as in other cancers with characteristic deletions or rearrangements of 1p36.
SourceAvailable from: Filipp Filippovich Vasilyev[Show abstract] [Hide abstract]
ABSTRACT: The level of TNF receptors on various cells of immune system and its association with the gene polymorphism were investigated. Determining the levels of membrane-bound TNF α receptors on peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry using BD QuantiBRITE calibration particles. Soluble TNF α receptor (sTNFRs) levels were determined by ELISA and genotyping was determined by PCR-RFLP. Homozygous TT individuals at SNP -609G/T TNFRI (rs4149570) showed lower levels of sTNFRI compared to GG genotype carriers. Homozygous carriers of CC genotype at SNP -1207G/C TNFRI (rs4149569) had lower expression densities of membrane-bound TNFRI on intact CD14(+) monocytes compared to individuals with the GC genotype. The frequency differences in the CD3(+) and CD19(+) cells expressing TNFRII in relation to SNP -1709A/T TNFRII (rs652625) in healthy individuals were also determined. The genotype CC in SNP -3609C/T TNFRII (rs590368) was associated with a lower percentage of CD14(+) cells expressing TNFRII compared to individuals with the CT genotype. Patients with rheumatoid arthritis had no significant changes in the frequencies of genotypes. Reduced frequency was identified for the combination TNFRI -609GT + TNFRII -3609CC only. The polymorphisms in genes represent one of cell type-specific mechanisms affecting the expression levels of membrane-bound TNF α receptors and TNF α -mediated signaling.Mediators of Inflammation 01/2014; 2014:745909. DOI:10.1155/2014/745909 · 2.42 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: We aimed to explore the association between the onset of ankylosing spondylitis (AS) and nt587 polymorphisms of the tumor necrosis factor receptor II (TNFRII) gene in the Han population of Hunan Province, China. Correlation analysis was performed in a case-control study involving 100 AS cases and 100 healthy controls. The nt587 single nucleotide polymorphism of the TNFRII gene was examined by polymerase chain reaction-restriction fragment length polymorphism. The relationship between AS and the frequencies of genotypes and alleles in TNFRII nt587 were analyzed using the SPSS software. There were 43 cases with the TNFRII nt587 T/T genotype, 32 cases with the TNFRII nt587 T/G genotype, and 25 cases with the TNFRII nt587 G/G genotype. In the 100 healthy controls, 56 subjects had the TNFRII nt587 T/T genotype, 34 had the TNFRII nt587 T/G genotype, and 10 had the TNFRII nt587 G/G genotype. The G allele frequency of the AS group was significantly higher (χ(2) = 8.734, P = 0.003) than that in the control group (41.0 vs 27.0%). The odds ratio (OR) in AS cases with the TNFRII nt587 G/G genotype was 3.256, which was obviously higher than in those with T/G (OR = 1.226) and T/T (OR = 1.0) genotype. The polymorphism at position nt587 of the TNFRII gene was found to be associated with AS, and the TNFRII nt587 G allele may play an important role in AS susceptibility. The TNFRII nt587 G/G genotype may increase the risk of developing AS in the Hunan population.Genetics and molecular research: GMR 01/2014; 13(3):5190-8. DOI:10.4238/2014.July.7.12 · 0.85 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.