Abstract
An assessment has been made of the polymorphism of human complement component C4 by comparing derived amino acid sequences of cDNA and genomic DNA with limited amino acid sequences. In all, one complete and six partial sequences have been obtained from material from three individuals and include two C4A and two C4B alleles. Differences were found between the 4 alleles from 2 loci in only 15 of the 1722 amino acid residues, and 12 lie within one section of 230 residues, which in 1 allele also contains a 3-residue deletion. In three variable positions, an allelic difference in one C4 type was common to the other types. Three nucleotide differences were found in four introns. In spite of marked differences in their chemical reactivity, the many allelic forms appear to differ in less than 1% of their amino acid residue positions. This unusual pattern of polymorphism may be due to recent duplication of the C4 gene, or may have arisen by selection as a result of the biological role of C4, which interacts in the complement sequence with nine other proteins necessitating conservation of much of the surface structure.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Belt, K.T., Carroll, M. C., and Porter, R. R.: The structural basis of the multiple forms of human complement component C4. Cell 36: 907–914, 1984
Biggin, M. D., Gibson, T. J., and Hong, G. F.: Buffer gradient gels and 35 S label as an aid to rapid DNA sequence determination. Proc. Natl. Acad. Sci. U.S.A. 83: 3963–3965, 1983
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, 1984a
Carroll, M. C., Belt, K. T., Palsdottir, A., and Porter, R. R.: Structure and organisation of the C4 genes. Philos. Trans. R. Soc. London B 306: 379–388, 1984b
Chakravarti, D. N., Campbell, R. D., and Gagnon, J.: Amino acid sequence of a polymorphic segment from fragment C4d of human complement component C4. FEBS Lett. 154: 387–390, 1983
Chan, A. C., Karp, D. R., Schreffler, D. C., and Atkinson, J. P.: The 20 faces of the fourth component of complement. Immunol. Today 5: 200–203, 1984
Grosveld, F. G., Lund, T., Murray, E. J., Mellor, A. L., Dahl, H., and Flavell, R. A.: The construction of cosmid libraries which can be used to transform eucaryotic cells. Nucleic Acids Res. 10: 6715–6731, 1982
Hauptmann, G., Goetze, J., Uring-Lamport, B., and Grosshaus, E.: Hereditary and acquired complement deficiencies in animals and men. Prog. Allergy, in press, 1985
Hellman, U., Eggertsen, G., Lundwall, A., Engstrom, A., and Sjoquist, J.: Primary sequence differences between Chido and Rodgers variants of tryptic C4d of the human complement system. FEBS Lett. 170: 254–258, 1984
Isenman, D. E. and Young, J. R.: The molecular basis for the difference in immune hemolysis activity of the Chido and Rodgers isotypes of human complement component C4. J. Immunol. 132: 3019–3027, 1984
Law, S. K. A., Dodds, A. W., and Porter, R. R.: A comparison of the properties of two classes, C4A and C4B, of the human complement component C4. EMBO J. 3: 1819–1823, 1984
Maniatis, T., Fritsch, E. F., and Sambrook, J.: Electrophoresis on to a dialysis membrane. In: Molecular Cloning, a Laboratory Manual, p. 168, Cold Spring Harbor, New York, 1982
Mauff, G., Alper, C. A., Awdeh, Z., Batchelor, J. R., Bertrams, T., Braun-Peterson, G., Dawkins, R. L., Demant, P., Edwards, J., Grosse-Wild, H., Hauptmann, G., Klonda, P., Lamm, L., Mullerhauer, E., Nerl, C., Olaiser, B., O'Neill, G. O., Rittner, C., Roos, M. H., Skanes, V., Teisberg, P., and Wells, L.: Statement on the nomenclature of human C4 allotypes. Immunobiology 164: 184–191, 1983
Messing, J. and Vieira, J.: A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene 19: 269–276, 1982
Nisonoff, A., Hopper, J. E., and Spring, S. B.: The Antibody Molecule, p. 378, Academic Press, New York, 1975
Sanger, F., Nicklen, S., and Coulson, A. R.: DNA sequencing with chain terminating inhibitors. Proc. Natl. Acad. Sci. U.S.A. 74: 5463–5468, 1977
Staden, R.: Automation of the computer handling of gel reading data produced by the shotgun method of DNA sequencing. Nucleic Acids Res. 10: 4731–4751, 1982
Whitehead, A. S., Woods, D. E., Fleischmek, E., Chin, J. E., Yunis, E., Katz, A. J., Gerald, P. S., Alper, C. A., and Colten, H. R.: DNA polymorphism of the C4 genes: A new marker for analysis of the major histocompatibility complex. N. Engl. J. Med. 320: 88–91, 1984
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tertia Belt, K., Yung Yu, C., Carroll, M.C. et al. Polymorphism of human complement component C4. Immunogenetics 21, 173–180 (1985). https://doi.org/10.1007/BF00364869
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00364869