Genomic organization of a polymorphic duplicated region centromeric of HLA-B. 1992

C Leelayuwat, and L J Abraham, and H Tabarias, and F T Christiansen, and R L Dawkins
Department of Clinical Immunology, Royal Perth Hospital, Western Australia.

The region between tumor necrosis factor (TNF) and HLA-B in the central major histocompatibility complex (MHC) is polymorphic and associated with several autoimmune diseases. The polymorphisms are haplospecific or haplotypic and retained within the same MHC ancestral haplotype (AH). We have cloned this region from four AHs into lambda bacteriophage and found that a highly polymorphic region in the TNF-HLA-B interval is duplicated. Clones from this region isolated from three MHC AHs show two populations. The regions, designated CL1 and CL2, have different sizes of Bam HI fragments carrying the duplicated sequences. These fragments correspond to those seen after Bam HI restriction fragment length polymorphism (RFLP) analysis of genomic DNA from the same cell lines. Pulsed field gel electrophoresis analysis shows that both CL1 and CL2 are in the central MHC and are about 16 kilobases apart. DNA cloning and RFLP analysis demonstrate that the CL region is highly polymorphic but retained within an MHC AH. Polymorphism and duplication are common characteristics of the genes found in the MHC and therefore the CL sequences have the potential to be interesting in this respect.

UI MeSH Term Description Entries
D008285 Major Histocompatibility Complex The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. Histocompatibility Complex,Complex, Histocompatibility,Complex, Major Histocompatibility,Complices, Histocompatibility,Complices, Major Histocompatibility,Histocompatibility Complex, Major,Histocompatibility Complices,Histocompatibility Complices, Major,Major Histocompatibility Complices
D012150 Polymorphism, Restriction Fragment Length Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment. RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D002503 Centromere The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. Centromeres
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D005810 Multigene Family A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed) Gene Clusters,Genes, Reiterated,Cluster, Gene,Clusters, Gene,Families, Multigene,Family, Multigene,Gene Cluster,Gene, Reiterated,Multigene Families,Reiterated Gene,Reiterated Genes
D001345 Autoradiography The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed) Radioautography
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D015235 HLA-B Antigens Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes. Antigens, HLA-B,HLA-B Antigen,HLA-B,Antigen, HLA-B,Antigens, HLA B,HLA B Antigen,HLA B Antigens
D016521 Electrophoresis, Gel, Pulsed-Field Gel electrophoresis in which the direction of the electric field is changed periodically. This technique is similar to other electrophoretic methods normally used to separate double-stranded DNA molecules ranging in size up to tens of thousands of base-pairs. However, by alternating the electric field direction one is able to separate DNA molecules up to several million base-pairs in length. Electrophoresis, Gel, Pulsed-Field Gradient,Gel Electrophoresis, Pulsed-Field,Contour-Clamped Homogeneous-Field Gel Electrophoresis,Electrophoresis, Gel, Pulsed Field,Electrophoresis, Pulsed Field Gel,Field Inversion Gel Electrophoresis,Orthogonal Field Alternation Gel Electrophoresis,Orthogonal-Field Alternation-Gel Electrophoresis,Pulsed Field Gradient Gel Electrophoresis,Pulsed-Field Gel Electrophoresis,Pulsed-Field Gradient Gel Electrophoresis,Alternation-Gel Electrophoresis, Orthogonal-Field,Contour Clamped Homogeneous Field Gel Electrophoresis,Electrophoresis, Orthogonal-Field Alternation-Gel,Electrophoresis, Pulsed-Field Gel,Gel Electrophoresis, Pulsed Field,Pulsed Field Gel Electrophoresis

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