Abstract
Using an exon-specific polymerase chain reaction (PCR) followed by direct DNA sequence analysis we have analyzed the polymorphism of the α-chain of the eighth component of human complement (C8) at the DNA level. We found that two common alleles, C8A*A and C8A*B, are characterized by the substitution of a single amino acid (Gln to Lys), which is caused by a point mutation of a single nucleotide (C to A) in exon 3 at position 187 of the mature C8α cDNA sequence. Based on this mutation, an allele-specific PCR was designed detecting the two alleles of C8A. We applied this method to type the C8A polymorphism using DNA samples from a Chinese Han population. The comparison with the data of protein typing of the same samples proved that the described method is efficient and reliable for the identification of C8A genotypes and may be valuable for further application in population studies and forensic science.
Similar content being viewed by others
References
Don RE, Cox PT, Wainright BJ, Baker K, Mattick JS (1991) “Touchdown” PCR to circumvent spurious priming during gene amplification. Nucleic Acids Res 19:4008
Kaufman KM, Snider JV, Spurr NK, Schwartz CE, Sodetz JM (1989) Chromosomal assignment of the genes encoding the α, β and γ subunits of human complement protein C: identification of a close physical linkage between the α and β locus. Genomics 5:475–480
Kaufman T, Hänsch G, Rittner C, Späth P, Tedesco F, Schneider PM (1993a) Genetic basis of human complement C8β deficiency. J Immunol 150:4943–4947
Kaufman T, Rittner C, Schneider PM (1993b) The human complement component C8β gene: structure and phylogenetic relationship. Hum Genet 92:69–75
Michelotti GA, Snider JV, Sodetz JM (1995) Genomic organization of human complement protein C8α and further examination of its linkage to C8β. Hum Genet 95:513–518
Rao AG, Howard OMZ, Ng SC, Whitehead AS, Colten HR, Sodetz JM (1987) cDNA and derived amino acid sequence of the alpha-subunit of human complement protein C 8: evidence for the existence of a separate alpha-subunit mRNA. Biochemistry 26:3556–3564
Raum D, Spence MA, Balavitch D, Tideman S, Merrit AD, Taggart RJ, Petersen BH, Day NK, Alper CA (1979) Genetic control of the eighth component of complement. J Clin Invest 64:858–865
Rittner C, Hargesheimer W, Mollenhauer E (1984) Population and formal genetics of the human C81 (α-γ) polymorphism. Hum Genet 67:166–169
Rittner C, Hargesheimer W, Stradmann B, Bertrams J, Baur MP, Petersen BH (1986) Human C81 (α-γ) polymorphism: detection in the a-g subunit on SDS-PAGE, formal genetics and linkage relationship. Am J Hum Genet 38:482–491
Rittner C, Stradmann-Bellinghausen B, Rogde S (1990) C8 reference typing report and nomenclature recommendation. Complement Inflamm 7:243–247
Rittner C, Stradmann-Bellinghausen B (1993) Human complement C81 (C8A) polymorphism: detection and segregation of new variants. Hum Genet 92:413–416
Rogde S, Mevag B, Teisberg P, Gedde-Dahl T Jr, Tedesco F, Olaisen B (1985) Genetic polymorphism of complement component C8. Hum Genet 70:211–216
Rogde S, Olaisen B, Gedde T Jr, Teisberg P (1986) The C8A and C8B loci are closely linked on chromosome 1. Am J Hum Genet 50:139–144
Rogde S, Olaisen B, Teisberg P, Sodetz J (1991) A BamHI RFLP of the C8A gene. Nucleic Acids Res 19:3762
Sodetz JM (1988) Structure and function of C8 in the membrane attack sequence of complement. Curr Top Microbiol Immunol 140:19–31
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zhang, L., Rittner, C., Sodetz, J.M. et al. The eighth component of human complement: molecular basis of C8A (C81) polymorphism. Hum Genet 96, 281–284 (1995). https://doi.org/10.1007/BF00210407
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00210407