Tandem Arrangement of Genes Coding for Tumor Necrosis Factor (TNF- ) and Lymphotoxin (TNF- ) in the Human Genome

Недоспасов, С А; Shakhov, Alexander N.; Turetskaya, Regina L.; Mett, Vadim; Azizov, Mekhman; Georgiev, G.P.; Коробко, В Г; Dobrynin, V. N.; Filippov, S. A.; Bystrov, N. S.; Boldyreva, E. F.; Chuvpilo, Sergei; Chumakov, Alexey M.; Shingarova, L. N.; Ovchinnikov, Yu.A.

doi:10.1101/sqb.1986.051.01.073

Cited by 117 publications

(69 citation statements)

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“…15), which transforms a 5.5-kb Nco I restriction fragment into a 10.5-kb restriction fragment. This was confirmed by our finding that probes for both TNFa and TNFP hybridized to the 5.5-kb and 10.5-kb Nco I restriction fragments (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Restriction fragment length polymorphism of the tumor necrosis factor region in patients with ankylosing spondylitis

Verjans

Kijlstra

Linden³

et al. 1991

Arthritis & Rheumatism

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Although ankylosing spondylitis (AS) is known to be strongly associated with the class I major histocompatibility complex antigen HLA-B27, B27 is probably not the only genetic factor involved in the pathogenesis of AS. Because of the involvement of tumor necrosis factor (TNF) in cartilage damage and the localization of the TNF genes in the proximity of the HLA-B locus, we investigated the association between AS and TNF alleles. The frequencies of the restriction fragment length polymorphisms linked to the TNF genes were determined in 73 AS patients and 81 controls. No differences were observed between AS patients and controls with respect to the frequencies of the TNF restriction fragment length polymorphisms.The histocompatibility antigen HLA-B27 is strongly associated with ankylosing spondylitis (AS) and related diseases (1). among Caucasian patients with AS is >90%, whereas HLA-B27 is present in only approximately 8% of the total Caucasian population. Although fewer than 2% of B27+ individuals will develop AS, the prevalence of AS among adult B27+ first-degree relatives of B27+ AS patients is at least tenfold higher (2). This difference has led to the hypothesis that other genetic factors besides HLA-B27 are involved in the pathogenesis of AS. These alleles are probably not located on the B27 haplotype, but rather, elsewhere in the genome (3,4). Recently, Robinson et a1 (5) have shown an increased susceptibility to AS among HLA-B27/ Bw60 heterozygous individuals. It has been suggested that an unknown subset of HLA-Bw60, or a gene in linkage disequilibrium with HLA-Bw60, might be involved in the pathogenesis of AS in these persons (5).Tumor necrosis factor a (TNFa) and TNFp are closely related cytokines with a broad range of biologic activities (6). Biologic effects of TNF include regulation of immune responses, such as induction of HLA antigen expression in cells, stimulation of collagenase and prostaglandin expression, and modulation of neutrophil-mediated cartilage damage (6). The TNF genes in humans are located within the class I11 major histocompatibility complex (MHC) region, close to the The link between TNF and regulation of the immune response, and the localization of the TNF genes, has led to the hypothesis that polymorphism in the TNF genes might play a role in the associations between HLA antigens and various diseases (7). Recently, it has been demonstrated that TNFa levels in humans are class I1 MHC associated, and are probably involved in the genetic predisposition to the develop-HLA-B IOCUS (7).

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Section: Resultsmentioning

confidence: 99%

Restriction fragment length polymorphism of the tumor necrosis factor region in patients with ankylosing spondylitis

Verjans

Kijlstra

Linden³

et al. 1991

Arthritis & Rheumatism

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“…An example of this is the tumour necrosis factor (TNF) family of ligands which comprises three adjacent, closely-related genes within the MHC region on chromosome 6 25 and many other genes on a variety of chromosomes, which continue to be uncovered. 26,27 More recently, the T-cell-derived cytokine IL-17 was shown to be the prototype for a new family of cytokines.…”

Section: Introductionmentioning

confidence: 99%

Cloning, expression and initial characterisation of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10)

et al. 2000

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“…TNFc is located in the first intron of the TNF-f3 gene (nucleotides 1238-1260 in ref. 5), while TNFa and TNFb are adjacent to each other in a region 3.5 kb upstream of the TNF-f3 mRNA start site (22). The primers that we used measure variations in the number of CA (TNFa) or CT (TNFb) repeats within this region.…”

Section: Resultsmentioning

confidence: 99%

Extensive genetic polymorphism in the human tumor necrosis factor region and relation to extended HLA haplotypes

1992

Parasitology Today

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We have identified three polymorphic microsatellites (which we call TNFa, TNFb, and TNFc) within a 12-kilobase region of the human major histocompatibility complex (MHC) that includes the tumor necrosis factor (TNF) locus. TNFc is located within the first intron of the TNF-gene and has only 2 alleles. TNFa and TNFb are 3.5 kilobases upstream (telomeric) of the TNF-P gene and have at least 13 and 7 alleles, respectively. TNFa, -b, and -c alleles are in linkage disequilibrium with alleles at other loci within the MHC, including class I, class II, and class m. TNFa, -b, and -c alleles are also associated with extended HLA haplotypes.These TNF polymorphisms will allow a thorough genetic analysis of the involvement of TNF in MHC-linked pathologies.The tumor necrosis factors (TNFs) have been recognized as essential mediators of the inflammatory response (1-3). The genes encoding TNF-a, the major macrophage-monocytederived form, and TNF-,3, which seems to be produced exclusively by lymphocytes, are located within a 7-kilobase (kb) region (4, 5), which we will henceforth designate as the TNF locus. The TNF locus is located within the major histocompatibility complex (MHC) of mouse and human (6, 7). In humans, TNF maps 320 kb centromeric to HLA-B (class I) and 340 kb telomeric to the C2/BF complex (class III) (8,9).The location of TNF within the MHC has prompted much speculation about the role of TNF alleles in the etiology of MHC-linked diseases, in particular those with an inflammatory or autoimmune component. This hypothesis has been difficult to test because of a lack of genetic markers in the locus: an extensive search for restriction fragment length polymorphisms (RFLPs) has yielded a biallelic Nco I RFLP (10-13) and a very rare EcoRI RFLP (14). In spite of its limited information content, the Nco I RFLP has already allowed some tentative associations between TNF alleles and autoimmune diseases (11, 15); recent evidence also suggests that one Nco I allele correlates with increased TNF-a and reduced TNF-13 production (13, 16).Microsatellite mapping is a recently developed technique in which the repeat number of a simple sequence element (usually a CA or CT dinucleotide) occurring at a unique location within the genome is measured after amplification by the PCR and used as an allelic marker (17). We have previously used this technique to define a multiallelic polymorphism within the mouse TNF locus (18). The present study extends this work to humans and defines three polymorphic regions that are in linkage disequilibrium with alleles at other MHC loci.

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Tandem Arrangement of Genes Coding for Tumor Necrosis Factor (TNF- ) and Lymphotoxin (TNF- ) in the Human Genome

Cited by 117 publications

References 0 publications

Restriction fragment length polymorphism of the tumor necrosis factor region in patients with ankylosing spondylitis

Restriction fragment length polymorphism of the tumor necrosis factor region in patients with ankylosing spondylitis

Cloning, expression and initial characterisation of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10)

Extensive genetic polymorphism in the human tumor necrosis factor region and relation to extended HLA haplotypes

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