, Volume 25, Issue 5, pp 299–304

Heterogeneity of human C4 gene size

A large intron (6.5 kb) is present in all C4A genes and some C4B genes
  • A. Palsdottir
  • R. Fossdal
  • A. Arnason
  • J. H. Edwards
  • O. Jensson


In this article we present a study showing that the human C4 genes differ in length because of the presence or absence of a 6.5 kb intron near the 5′ end of the gene. DNA from individuals of known HLA, factor B, and C4 haplotypes was analyzed for restriction fragment length polymorphism (RFLP) by Southern blot analysis with C4-specific cDNA probes. The RFLP patterns obtained showed that the C4 genes are either 22.5 kb or 16 kb in length. They are referred to as long and short C4 genes, respectively. A population study was carried out to examine the distribution of the gene size according to C4 allotypes and haplotypes. Long C4 genes included all C4A genes studied and also some C4B allotypes, e. g., B1 on most C4 A3B1 haplotypes. Similarly, C4B null genes were found to be of the long form. Other C4B allotypes tested were found to be coded for by short C4 genes, including B2, B1 in C4 A6B1 and C4 AQOB1 (with a single C4B gene haplotype).

Abbreviations used in this paper


fourth component of complement


second component of complement


factor B


major histocompatibility complex


restriction fragment length polymorphism


ethylenediaminetetraacetic acid


lauryl sulfate, sodium salt


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  1. Alper, C. A., Boenisch, T., and Watson, L.: Genetic polymorphism in the human glycine-rich beta-glycoprotein. J. Exp. Med. 135: 68–80, 1972CrossRefPubMedGoogle Scholar
  2. Awdeh, Z. L. and Alper, C. A.: Inherited structural polymorphism of the fourth component of human complement. Proc. Natl. Acad. Sci. U.S.A. 77: 576–3580, 1980Google Scholar
  3. Awdeh, Z. L., Raum, D., Yunis, E. J., and Alper, C. A.: Extended HLA/complement allele haplotypes: Evidence for T/t-like complex in man. Proc. Natl. Acad. Sci. U.S.A. 80: 259–263, 1983PubMedGoogle Scholar
  4. Bell, G. I., Karem, J. H., and Rutter, W. J.: Polymorphic DNA region adjacent to the 5′ end of the human insulin gene. Proc. Natl. Acad. Sci. U.S.A. 78: 5759–5763, 1981PubMedGoogle Scholar
  5. Belt, K. T., Carroll, M. C., and Porter, R. R.: The structural basis of the multiple forms of human complement C4. Cell 36: 907–914, 1984CrossRefPubMedGoogle Scholar
  6. Belt, K. T., Yu, C. Y., Carroll, M. C., and Porter, R. R.: Polymorphism of human complement component C4. Immunogenetics 21: 173–180, 1985PubMedGoogle Scholar
  7. Bruun-Petersen, G., Lamm, L. U., Jacobsen, B. K., and Kristensen, T.: Genetics of human complement C4. Two homoduplication haplotypes C4S, C4S and C4F, C4F in a family. Hum. Genet. 61: 36–38, 1982CrossRefPubMedGoogle Scholar
  8. Carroll, M. C. and Porter, R. R.: Cloning of a human complement component C4 gene. Proc. Natl. Acad. Sci. U.S.A. 80: 264–267, 1983PubMedGoogle Scholar
  9. Carroll, M. C., Campbell, R. D., Bentley, D. R., and Porter, R. R.: A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature 307: 237–241, 1984aPubMedGoogle Scholar
  10. Carroll, M. C., Belt, K. T., Palsdottir, A., and Porter, R. R.: Structure and organization of the C4 genes. Philos. Trans. R. Soc. Lond. (Biol.) 306: 379–388, 1984bGoogle Scholar
  11. Carroll, M. C., Campbell, R. D., and Porter, R. R.: Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man. Proc. Natl. Acad. Sci. U.S.A. 82: 521–525, 1985aPubMedGoogle Scholar
  12. Carroll, M. C., Palsdottir, A., Belt, K. T., and Porter, R. R.: Deletion of complement C4 and steroid 21-hydroxylase genes in the HLA class III region. EMBO J. 4: 2547–2552, 1985bPubMedGoogle Scholar
  13. Carroll, M. C., Belt, K. T., Palsdottir, A., and Yu, Y.: Molecular genetics of the fourth component of human complement and steroid 21-hydroxylase. Immunol. Rev. 87: 39–60, 1985cPubMedGoogle Scholar
  14. Garlepp, M. J., Wilton, A. N., Dawkins, R. L., and White, P. C.: Rearrangement of 21-hydroxylase genes in disease-associated MHC supratypes. Immunogenetics 23: 100–105, 1986PubMedGoogle Scholar
  15. Hauptmann, G., Goetz, J., Uring-Lambert, B., and Grosshans, E.: C4 deficiency. In: Progress in Allergy: Hereditary and Acquired Complement Deficiencies in Animals and Men, in press, 1987Google Scholar
  16. Lamm, L. U. and Olaisen, B.: Report of the committee on the genetic constitution of chromosomes 5 and 6. Cytogenet. Cell Genet. 40: 128–155, 1985PubMedGoogle Scholar
  17. Mauff, G., Alper, C. A., Awdeh, Z., Batchelor, J. R., Bertrams, J., Bruun-Petersen, G., Dawkins, R. L., Demant, P., Edwards, J., Grosse-Wilde, H., Hauptmann, G., Klouda, P., Lamm, L., Mollenhauer, E., Nerl, C., Olaisen, B., O'Neill, G., Rittner, C., Roos, M. H., Skanes, V., Teisberg, P., and Wells, L.: Statement on the nomenclature of human C4 allotypes. Immunobiology 164: 184–191, 1983PubMedGoogle Scholar
  18. Nonaka, H., Nakayama, K., Yeul, Y. D., Shimizu, A., and Takahashi, M.: Molecular cloning and characterization of complementary and genomic DNA clones for C4 and Slp. Immunol. Rev. 87: 81–99, 1985PubMedGoogle Scholar
  19. Palsdottir, A., Cross, S. J., Edwards, J. H., and Carroll, M. C.: Correlation between a DNA restriction fragment length polymorphism and C4A6 protein. Nature 306: 615–616, 1983PubMedGoogle Scholar
  20. Palsdottir, A., Arnason, A., Fossdal, R., and Jensson, O.: Gene organization of haplotypes expressing two different C4A allotypes. Hum. Genet., in press, 1987Google Scholar
  21. Prentice, H. L., Schneider, P. M., and Strominger, J. L.: C4B gene polymorphism detected in a human cosmid clone. Immunogenetics 23: 274–276, 1986PubMedGoogle Scholar
  22. Raum, D., Awdeh, Z. L., Anderson, J., Strong, L., Granados, J., Pevan, L., Giblett, E., Yunis, E. J., and Alper, C. A.: Human C4 haplotypes with duplicated C4A or C4B. Am. J. Hum. Genet. 36: 72–79, 1984PubMedGoogle Scholar
  23. Rittner, C., Hauptmann, G., Grosse-Wilde, H., Grosshans, E., Tongio, M. M., and Mayer, S.: Linkage between HL-A (major histocompatibility complex) and genes controlling synthesis of the fourth component of complement. In F. Kissmeyer-Nielsen (ed.): Histocompatibility Testing, pp. 945–953, Munksgaard, Copenhagen, 1975Google Scholar
  24. Rittner, C., Giles, C. M., Roos, M. H., Demant, P., and Mollenhauer, E.: Genetics of human C4 polymorphism: Detection and segregation of rare and duplicated haplotypes. Immunogenetics 19: 321–333, 1984PubMedGoogle Scholar
  25. Schendel, D. J., O'Neill, G. J., and Wank, R.: MHC-linked class III genes. Analysis of C4 gene frequencies, complotypes and associations with distinct HLA haplotypes in German Caucasians. Immunogenetics 20: 23–31, 1984PubMedGoogle Scholar
  26. Schneider, P. M., Carroll, M. C., Alper, C. A., Rittner, C., Whitehead, A. S., Yunis, E. J., and Colten, H. R.: Polymorphism of the human complement C4 and steroid 21-hydroxylase genes. Restriction fragment length polymorphism revealing structural deletions, homoduplications, and size variants. J. Clin. Invest. 78: 650–657, 1986PubMedGoogle Scholar
  27. Singer, M. F. and Skowronski, J.: Making sense out of LINES: Long interspersed repeat sequences in mammalian genomes. TIBS 10: 119–122, 1985Google Scholar
  28. Southern, E. M.: Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98: 503–517, 1975PubMedGoogle Scholar
  29. Uring-Lambert, B., Goetz, J., Tongio, M. M., Mayer, S., and Hauptmann, G.: C4 haplotypes with duplications at the C4A and C4B loci: Frequency and associations with BF, C2 and HLA-A, B, C, Dr alleles. Tissue Antigens 24: 70–72, 1984PubMedGoogle Scholar
  30. White, P. C., Grossberger, D., Onufer, B. J., Chaplin, D. D., New, M. I., Dupont, B., and Strominger, J. L.: Two genes encoding the fourth component of complement in man. Proc. Natl. Acad. Sci. U.S.A. 82: 1089–1093, 1985PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • A. Palsdottir
    • 1
  • R. Fossdal
    • 2
  • A. Arnason
    • 2
  • J. H. Edwards
    • 3
  • O. Jensson
    • 2
  1. 1.MRC Immunochemistry Unit, Department of BiochemistryUniversity of OxfordOxfordEngland
  2. 2.Genetics DivisionThe Blood BankReykjavikIceland
  3. 3.Genetics Laboratory, Department of BiochemistryUniversity of OxfordOxfordEngland

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