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S Rodriguez de Cordoba

Publications and source records attributed to S Rodriguez de Cordoba.

At least 19 recordsLinked to original sources
PubMed1996

Ordering of the human regulator of complement activation gene cluster on 1q32 by two-colour FISH.

The regulator of complement activation (RCA) gene cluster and PTPRC and REN genes have been mapped to the 1q31-->q32 band interval. We have used two-colour in situ hybridization to determine the chromosomal position of these genes. We report here that HF1/F13B are proximal to the C4BP/MCP genes. We also propose that PTPRC and REN genes map to a region of the RCA gene cluster between the HF1/F13B and C4BP/MCP regions. In summary, we propose the following gene order: centromere-HF1/F13B-PTPRC-REN-C4BP/MCP-telomere.

Chromosome Mapping↗
PubMed1993

The human C4b-binding protein beta-chain gene.

Human complement component C4b-binding protein (C4BP) is composed of seven alpha-chains and one beta-chain. The alpha- and beta-chains are homologous and both contain multiple copies of short consensus repeats (SCR) and in addition carboxyl-terminal non-repeat regions. Each of the alpha-chains contains a binding site for C4b, whereas the beta-chain binds protein S, a vitamin K-dependent protein involved in the regulation of blood coagulation. The alpha- and beta-chain genes are closely linked in the regulators of complement activation gene cluster on the long arm of human chromosome 1, band 1q32. The human beta-chain gene which has now been characterized was found to span more than 10 kilobases of DNA. The presence of at least two different beta-chain gene transcripts was suggested by the isolation of two new cDNA clones which contained different sequences in their extended 5'-untranslated regions. Northern blot analysis demonstrated that the two clones represented distinct beta-chain mRNAs with different 5' end sequences. One class of beta-chain mRNA (denoted A19) was found to be encoded by six exons and primer extension, and S1 nuclease protection assays revealed multiple closely spaced transcription start sites for this mRNA class. Its 5'-untranslated region and signal peptide was encoded by the first exon. The second class of mRNA (denoted A12) had a different transcription start site and its 5'-untranslated region was derived from at least three exons out of which the last one was formed by utilization of an acceptor splice site within the first A19 exon. Exons encoding the mature beta-chain and the 3'-untranslated region were common to both classes of mRNA. The beta-chain contains three SCRs, out of which the first and second are encoded by individual exons, whereas two exons encode the third SCR. The exon encoding the carboxyl-terminal part of the third SCR also encodes 14 amino acids of the non-repeat region. The last exon encodes the remaining 46 carboxyl-terminal amino acids and the entire 3'-untranslated region. The elucidation of the organization of the beta-chain gene provides insight into the sophisticated molecular structure of C4BP and a basis for future structural and functional studies.

Amino Acid Sequence↗
PubMed1991

Structure of the gene coding for the alpha polypeptide chain of the human complement component C4b-binding protein.

The human gene coding for the 70-kD polypeptide of the complement regulatory component C4b-binding protein (C4BP alpha) spans over 40 kb of DNA and is composed of twelve exons. Upon transcription in liver, or in Hep-G2 cells, this gene produces a single transcript of 2,262 nucleotides, excepting the poly A tail, that presents an unusually long 5' untranslated region (5' UTR) of 223 nucleotides. The C4BP alpha gene is organized as follows: the first exon codes for the first 198 nucleotides of the 5' UTR. It is separated by a large intron from the second exon including the remaining of the 5' UTR and the coding region for the signal peptide. Each of the eight 60-amino acid repeats (short consensus repeats [SCRs]) that compose the C4BP alpha polypeptide chain is encoded by a single exon, except for the second SCR, which is split in two exons. At the 3' end of the C4BP alpha gene, the twelfth exon codes for the COOH-terminal 57 amino acids of the mature protein, which have no similarities to the SCRs, and the 245 nucleotides of the 3' UTR. Examination of the nucleotide sequence of the first exon revealed an interesting characteristic, strongly suggesting that this exon may specify a functional domain of the C4BP alpha transcript. It includes two in-phase ATG codons, in a different frame respect to that coding the C4BP alpha polypeptide, followed by an in-frame termination codon, also within the first exon. Comparison between mouse and human C4BP alpha transcripts indicates conservation of this structure within the 5' UTR. C4BP is expressed in the liver and is an acute phase protein. A computer search of the genomic sequences upstream the transcription start site demonstrates the presence of potential cis-acting regulatory elements similar to those found in the promoters of other liver-expressed and/or acute phase genes.

Amino Acid Sequence↗
PubMed1990

Human genes for the alpha and beta chains of complement C4b-binding protein are closely linked in a head-to-tail arrangement.

C4b-binding protein (C4BP) is an important component in the regulation of the complement system and also binds the anticoagulant vitamin K-dependent protein S. These activities are performed by distinct, although structurally related, polypeptides of 70 kDa (alpha chain) and 45 kDa (beta chain), respectively. In this report we have investigated the genetic relationships between these polypeptides. Using pulsed field gel electrophoresis analysis we demonstrate that the genes coding for the alpha (C4BP alpha) and beta (C4BP beta) chains are closely linked within the regulator of complement activation gene cluster. In addition, we have determined that the 3' end of the C4BP beta gene lies 3.5-5 kilobases from the 5' end of the C4BP alpha gene. These findings support the concept that the C4BP alpha and C4BP beta genes are the result of a gene duplication event.

Carrier Proteins↗
PubMed1989

Molecular characterization by high resolution isoelectric focusing of the products encoded by the class II region loci of the MHC in humans. II. DP alpha and DP beta gene variants.

To characterize the molecular polymorphism of the DP alpha and DP beta gene products, the HLA-DP molecules expressed by more than 200 cell lines were individually immunoprecipitated by using the mAb B7/21 and their neuraminidase-treated DP alpha and DP beta chains analyzed in IEF gels. These cell lines, most of them from members of 32 families, allowed the definition, by segregation analysis, of the IEF patterns of the DP polypeptide chains encoded by 129 distinct haplotypes. Both DP alpha and DP beta chains display polymorphic IEF-banding patterns. Two DP alpha (A and B) and seven DP beta (A, B, C, D, E, F, and G) IEF variants were characterized. The DP alpha B variant was found in linkage disequilibrium with both DP beta B and DP beta D. Linkage disequilibrium was also encountered with alleles at the DR and DQ loci. Finally, the correlations between the IEF DP alpha and DP beta variants and the primed lymphocyte test-defined HLA-DP specificities were determined by using a panel of 24 primed lymphocyte test-typed cell lines.

Antibodies, Monoclonal↗
PubMed1989

Definition of IDDM-associated HLA DQ and DX RFLPs by segregation analysis of multiplex sibships.

Genetic variation of the DQ alpha and beta and of the DX alpha genes, detectable as RFLP in genomic DNA digests, has been suggested to improve the identification of individuals at high risk for insulin-dependent diabetes mellitus (IDDM). DNA from all members of 32 IDDM multiplex families was digested with six restriction endonucleases and the resulting fragments analyzed in Southern blots for hybridization with labeled cDNA probes for those genes. A computerized segregation analysis procedure was then used to assign fragments to haplotypes. Associations among fragments and between fragments and haplotypes characterized serologically and biochemically for their class II genes and IDDM-carrier status were calculated. The results indicate that the alleles of the DX alpha polymorphism maintain linkage disequilibrium with those of the DQ beta genes responsible for the well-known DQ beta 3.2-IDDM association, so that IDDM-carrier haplotypes carry disproportionally often both DQ beta 3.2 and DX alpha-TaqI-2.2kb. Thus, these RFLPs identify a DR-DQ-DX haplotype in high linkage disequilibrium, rather than the locus or loci that account for their high relative risk. However, four DR4-DQ beta 3.2 haplotypes that lack DX alpha-TaqI-2.2kb were encountered, two of which are "affected." These haplotypes suggest that the identification of the "disease locus" can be facilitated by the study of unusual haplotypes in which distinct IDDM-associated alleles occur separated from their neighbors of the standard genetic configurations.

Alleles↗
PubMed1988

A physical map of the human regulator of complement activation gene cluster linking the complement genes CR1, CR2, DAF, and C4BP.

We report the organization of the human genes encoding the complement components C4-binding protein (C4BP), C3b/C4b receptor (CR1), decay accelerating factor (DAF), and C3dg receptor (CR2) within the regulator of complement activation (RCA) gene cluster. Using pulsed field gel electrophoresis analysis these genes have been physically linked and aligned as CR1-CR2-DAF-C4BP in an 800-kb DNA segment. The very tight linkage between the CR1 and the C4BP loci, contrasted with the relative long DNA distance between these genes, suggests the existence of mechanisms interfering with recombination within the RCA gene cluster.

CD55 Antigens↗
PubMed1987

A new human Duffy blood group specificity defined by a murine monoclonal antibody. Immunogenetics and association with susceptibility to Plasmodium vivax.

A new Duffy specificity, Fy6, defined by a murine monoclonal antibody of the IgG1 kappa class, is related to susceptibility to malarial invasion. In humans, Fy6 is present on the red cells of all persons except those of the Fy(a-b-) type, a distribution resembling that of Fy3. However proteolytic enzyme treatment of red cells enhances the reactivity of Fy3, whereas Fy6, like Fya and Fyb, is susceptible to degradation by this process. The number of Fy6 sites on human red cells was found to be 12,200 per cell, in close agreement with earlier estimates of the number of Fya sites. Anti-Fy6 reacted in western blots with a membrane glycoprotein of approximately 46,000 Mr, not significantly different from that of a molecule known to bear the Fya determinant. The Fy6 epitope is shown to be present on the red cells of some but not all nonhuman primate species, where it has a distribution not only distinctly different from Fya, Fyb, and Fy3, but in close accordance with susceptibility to penetration by Plasmodium vivax. Thus, the red cells of two species of macaques (Macaca mulatta and M. fascicularis), which are invaded by Plasmodium knowlesi but not by P. vivax are shown to have other Duffy antigens but to be devoid of Fy6. It appears, therefore, that the red cell epitopes used by these closely related species are distinct, and that susceptibility to P. vivax merozoite penetration is dependent on the presence of Fy6.

Animals↗
PubMed1987

Decay-accelerating factor. Genetic polymorphism and linkage to the RCA (regulator of complement activation) gene cluster in humans.

We have investigated the genetic relationships between the human decay-accelerating factor (DAF) and a group of complement components including the C3b/C4b receptor (CR1), C4-binding protein (C4bp), and factor H (H), to which DAF is structurally and functionally related. CR1, C4bp, and H were previously demonstrated to be encoded by a cluster of closely linked genes, which we have designated regulator of complement activation (RCA). Southern blot analysis of genomic DNA using a DAF cDNA probe unraveled the existence of restriction fragment length polymorphism (RFLP) for both Bam HI and Hind III restriction endonucleases. Segregation analysis of these polymorphic fragments in families informative for the segregation of alleles at the CR1, C4BP, and H loci (RCA-haplotypes), demonstrated that, in humans, the gene encoding DAF is located within the RCA gene cluster. No recombinants between DAF and C4BP/CR1 were encountered in 32 informative meioses. In addition, in two individuals showing recombination between the CR1/C4BP and H loci, DAF segregated with the CR1/C4BP segment. Thus, the DAF gene maps closer to the CR1/C4BP loci than to the H gene, from which it can be separated by genetic recombination.

CD55 Antigens↗
PubMed1987

Molecular characterization by high-resolution isoelectric focusing of the products encoded by the class II region loci of the major histocompatibility complex in humans. I. DR and DQ gene variants.

We describe a new approach to the analysis of the structural polymorphism of the DR beta, DQ alpha, and DQ beta polypeptide chains of human histocompatibility class II antigens. In comparison to conventional two-dimensional gel studies, this method provides sharper definition of the protein bands and side-by-side comparisons within the same gel, thereby permitting the detection of minor differences in the isoelectric points of the protein chains. Using this methodology we have analyzed the IEF polymorphism and the variability in the number of the DR beta chains encoded by different DR haplotypes. Twenty DR beta chain variants, which include the products of no less than two separate DR beta loci, have been thus far identified. Alleles at one of these loci are assumed to code for DR beta chains carrying the DR alloespecificities DR1, DR2, DR3, DR4, DR5, DRw6, DR7, and DR8. Alleles at a second DR beta locus encode DR beta chains that may be shared by serologically DR-different haplotypes and carry supertypic serologic specificities (i.e., DRw52 and DRw53). We also demonstrate here that the structural polymorphisms of the DQ alpha and DQ beta chains are more extensive than previously thought, report the characterization of 14 DQ beta variants, and define their relationship to the previously described DQw serologic specificities. In addition, we describe the class II haplotype associations observed for the different DR and DQ variants characterized.

Alleles↗
PubMed1987

Occurrence of specific phytohaemagglutinin-reactive immunoglobulins in the sera of certain individuals. Relevance to the detection of cell surface antigens on phytohaemagglutinin-stimulated cells.

While investigating sera for possible antibodies to TL-like determinants, multiparous sera were selected that had specific cytotoxic reactivity against phytohaemagglutinin (PHA)-activated lymphocytes of certain individuals and were negative against unstimulated T or B cells from the same donor. The reactivity patterns were not correlated to any HLA specificities. However, in an indirect immunofluorescence assay with flow cytometry, these same sera had strong specific monomorphic reactivity to PHA-activated lymphocytes from all the individuals in the panel. Unstimulated cells remained negative. In contrast, other human sera lacked reactivity with PHA-stimulated lymphocytes. The addition of PHA to fresh lymphocytes followed by incubation at 4 degrees C for 30 min resulted in the same pattern of reactive and non-reactive sera. When incubated with PHA, different cell types, including 0- erythrocytes and a murine lymphoid cell line, reacted similarly with the sera. Using plates coated directly with PHA-E, L, and P in a cell-free ELISA system. PHA-specific sera reacted specifically with PHA-coated wells. The anti-PHA activity was removed by absorption with 0- erythrocytes coated with PHA without affecting the titre of the anti-HLA antibody in the same serum. These findings suggested that IgG molecules in certain sera react directly with residual PHA bound to the cell surface and not necessarily with molecules of cellular origin induced by exposure to PHA, complicating the search for antibodies specific for T-cell activation antigens.

Antibody Specificity↗