DNA Polymorphism of the Human Complement C8 Beta Gene: Formal Genetics and Intragenic Localization

Overview

Journal Immunogenetics

Specialties Allergy & Immunology
Genetics

Date 1989 Jan 1

PMID 2571588

Citations 2

Authors

D Herrmann

J M Sodetz

C Rittner

P M Schneider

Affiliations

Soon will be listed here.

Abstract

The eighth component of human complement consists of three subunits of different molecular mass, which are coded for by three separate genetic loci. Polymorphisms have been described at the protein level for the alpha and beta subunits by means of sodium dodecyl sulfate gel electrophoresis and isoelectric focusing. Using a full-length human C8 beta cDNA probe, we have studied more than 100 individuals by Southern blot analysis to detect DNA polymorphisms. We have found two restriction fragment length polymorphisms (RFLPs) with the enzymes Taq I and Bam HI. The Taq I polymorphism is defined by two alleles, i.e., a single 4.9 kb fragment or two 2.8/2.1 kb fragments. The allele frequencies are 0.68 and 0.32, respectively. The second RFLP with Bam HI is correlated with the Taq I variants: 3 kb Bam HI; 4.9 kb Taq I and 3.3 kb Bam HI; 2.8/2.1 kb Taq I. Both RFLPs could be mapped to the 3' portion of the C8 beta gene. Based on the size of genomic restriction fragments, the C8 beta gene can be estimated to have a size of 32-36 kb. Because of the even frequency distribution, the C8 beta DNA polymorphisms may be useful in gene mapping and disease association studies.

Citing Articles

Hypervariability generated by natural selection in an extracellular complement-inhibiting protein of serotype M1 strains of group A Streptococcus.

Stockbauer K, Grigsby D, Pan X, Fu Y, Mejia L, Cravioto A Proc Natl Acad Sci U S A. 1998; 95(6):3128-33.

PMID: 9501227 PMC: 19706. DOI: 10.1073/pnas.95.6.3128.

The human complement component C8B gene: structure and phylogenetic relationship.

Kaufmann T, Rittner C, Schneider P Hum Genet. 1993; 92(1):69-75.

PMID: 8365729 DOI: 10.1007/BF00216147.

References

Rigby P, Dieckmann M, Rhodes C, Berg P . Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977; 113(1):237-51. DOI: 10.1016/0022-2836(77)90052-3. View

Rogde S, Olaisen B, Gedde-Dahl Jr T, Teisberg P . The C8A and C8B loci are closely linked on chromosome 1. Ann Hum Genet. 1986; 50(2):139-44. DOI: 10.1111/j.1469-1809.1986.tb01032.x. View

Howard O, Rao A, Sodetz J . Complementary DNA and derived amino acid sequence of the beta subunit of human complement protein C8: identification of a close structural and ancestral relationship to the alpha subunit and C9. Biochemistry. 1987; 26(12):3565-70. DOI: 10.1021/bi00386a047. View

Rao A, Howard O, Ng S, WHITEHEAD A, Colten H, Sodetz J . Complementary DNA and derived amino acid sequence of the alpha subunit of human complement protein C8: evidence for the existence of a separate alpha subunit messenger RNA. Biochemistry. 1987; 26(12):3556-64. DOI: 10.1021/bi00386a046. View

Rittner C, Hargesheimer W, Mollenhauer E . Population and formal genetics of the human C81(alpha-gamma) polymorphism. Hum Genet. 1984; 67(2):166-9. DOI: 10.1007/BF00272993. View

Tedesco F, Densen P, Villa M, Petersen B, Sirchia G . Two types of dysfunctional eighth component of complement (C8) molecules in C8 deficiency in man. Reconstitution of normal C8 from the mixture of two abnormal C8 molecules. J Clin Invest. 1983; 71(2):183-91. PMC: 436856. DOI: 10.1172/jci110758. View

Miller S, Dykes D, Polesky H . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. PMC: 334765. DOI: 10.1093/nar/16.3.1215. View

Rogde S, Mevag B, Teisberg P, Gedde-Dahl Jr T, Tedesco F, Olaisen B . Genetic polymorphism of complement component C8. Hum Genet. 1985; 70(3):211-6. DOI: 10.1007/BF00273444. View

Tedesco F, Bardare M, Giovanetti A, Sirchia G . A familial dysfunction of the eight component of complement (C8). Clin Immunol Immunopathol. 1980; 16(2):180-91. DOI: 10.1016/0090-1229(80)90202-0. View

10.

Raum D, Spence M, Balavitch D, Tideman S, MERRITT A, Taggart R . Genetic control of the eighth component of complement. J Clin Invest. 1979; 64(3):858-65. PMC: 372192. DOI: 10.1172/JCI109534. View

11.

Klob W, MULLER-EBERHARD H . The membrane attack mechanism of complement: the three polypeptide chain structure of the eigth component (C8). J Exp Med. 1976; 143(5):1131-9. PMC: 2190193. DOI: 10.1084/jem.143.5.1131. View

12.

Southern E . Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975; 98(3):503-17. DOI: 10.1016/s0022-2836(75)80083-0. View

13.

Monahan J, Sodetz J . Binding of the eighth component of human complement to the soluble cytolytic complex is mediated by its beta subunit. J Biol Chem. 1980; 255(22):10579-82. View

14.

Ng S, Rao A, Howard O, Sodetz J . The eighth component of human complement: evidence that it is an oligomeric serum protein assembled from products of three different genes. Biochemistry. 1987; 26(17):5229-33. DOI: 10.1021/bi00391a003. View

15.

Steckel E, York R, Monahan J, Sodetz J . The eighth component of human complement. Purification and physicochemical characterization of its unusual subunit structure. J Biol Chem. 1980; 255(24):11997-2005. View

16.

Rittner C, Hargesheimer W, Stradmann B, Bertrams J, Baur M, Petersen B . Human C81 (alpha-gamma) polymorphism: detection in the alpha-gamma subunit on SDS-PAGE, formal genetics and linkage relationship. Am J Hum Genet. 1986; 38(4):482-91. PMC: 1684811. View

17.

Alper C, Marcus D, Raum D, Petersen B, Spira T . Genetic polymorphism in C8 beta-chains. Evidence for two unlinked genetic loci for the eighth component of human complement (C8). J Clin Invest. 1983; 72(5):1526-31. PMC: 370440. DOI: 10.1172/JCI111111. View

18.

Kaufman K, Snider J, Spurr N, Schwartz C, Sodetz J . Chromosomal assignment of genes encoding the alpha, beta, and gamma subunits of human complement protein C8: identification of a close physical linkage between the alpha and the beta loci. Genomics. 1989; 5(3):475-80. DOI: 10.1016/0888-7543(89)90012-8. View