Abstract
Class III gene rearrangements have been examined in Thai/Chinese individuals with supratypes bearing defective or null C4 alleles. Genomic DNA from C4 null supratypes was probed with an almost full-length 21-OH probe following digestion with Taq I and Kpn I. The HLA-B17 C4A3 BQO BfS DR3 Thai/Chinese supratypes (which may be associated with insulin-dependent diabetes mellitus in Orientals) lacks a 3.2 kb Taq I and a 3.9 kb Kpn I fragment hybridizing with the 21-OH probe. Similar gene rearrangements are found in Caucasoid diabetogenic supratypes HLA-B18 C4A3 BQO BfF1 DR3 and HLA-B8 C4AQ0 BI BfS DR3. Interethnic comparisons suggest that class II and class III interactions may be important in disease susceptibility. By contrast, neither of two Thai/Chinese supratypes with C4AQ0 appear to have major class III gene rearrangements; disease association studies will determine the significance of C4deficiency per se. As in Caucasoids, the electrophoretically fast C4 allele, C4A6, in Orientals has been shown to correlate with a 12 kb Bg1 II fragment hybridizing with a C4 probe. It is likely that the HLA-B17 C4A6 BI BfS DR7 supratype marks a highly conserved MHC chromosomal segment.
Similar content being viewed by others
References
Aizawa, M., Natori, T., Wakisaka, A., and Konoeda, Y. (eds.): In: HLA in Asia Oceania. Proceeding of the Third Asia Oceania Histocompatibility Workshop Conference, in press, Hokkaido University Press, Sapporo, 1986
Bertrams, J., Sodemann, P., Gruneklee, D., and Gries, F. A.: Bf in early onset insulin dependent diabetes. Lancet 2: 1240, 1979
Carroll, M. C. and Porter, R. R.: Cloning of a human complement C4 gene. Proc. Natl. Acad. Sci. U.S.A. 80: 264–267, 1983
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, 1985
Chan, S. H. and Feng, P. H.: HLA and systemic lupus erythematosus in Chinese. In R. L. Dawkins, F. T. Christiansen, and P. J. Zilko (eds.): Immunogenetics in Rheumatology, pp. 223–225, Excerpta Medica, Amsterdam, 1982
Cobain, T. J., Stuckey, M. S., McCluskey, J., Wilton, A. N., Gedeon, A., Garlepp, M. J., Christiansen, F. T., and Dawkins, R. L.: The coexistence of IgA deficiency and 21-hydroxylase deficiency marked by specific MHC supratypes. Ann. N.Y. Acad. Sci. 458: 76–84, 1985
Dawkins, R. L.: Concepts and models. Introduction. In R. L. Dawkins, F. T. Christiansen, and P. J. Zilko (eds.): Immunogenetics in Rheumatology, pp. 1–5, Excerpta Medica, Amsterdam, 1982
Dawkins, R. L., Christiansen, F. T., Kay, P. H., Garlepp, M. J., McCluskey, J., Hollingsworth, P. N., and Zilko, P. J.: Disease associations with complotypes supratypes and haplotypes. Immunol. Rev. 70: 5–22, 1983
Dawkins, R. L., Martin, E., Cobain, T. J., Kay, P. H., and Christiansen, F. T.: Supratypes as markers of disease genes and major histocompatibility complex class III genes. In T. Sasazuki (ed.): New Approach to Genetic Diseases, in press, Academic Press, Tokyo, 1987
Donohoue, P. A., Jospe, N., Migeon, C. J., McLean, R. H., Bias, W., White, P. C., and Van Dop, C.: Restriction maps and restriction fragment length polymorphisms of the human 21-hydroxylase genes. Biochem. Biophys. Res. Commun. 136: 722–729, 1986
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, 1986
Hawkins, B. R., Tiwari, J. L., Lowe, N., Wolfish, P., Pollack, C. A., Cho, Y. W., and Terasaki, P. I.: HLA and psoriasis. In P. I. Terasaki (ed.): Histocompatibility Testing 1980, pp. 711–714, UCLA Tissue Typing Laboratory, Los Angeles, 1980
Kay, P. H., Grimsley, G., Dawkins, R. L., and Charoenwong, P.: MHC supratypes as markers of null and defective C4 alleles in a Thai/Chinese population: relevance to disease susceptibility. Disease Markers 5: 43–47, 1987
Kelly, H., McCann, V. J., Kay, P. H., Wilton, A. N., and Dawkins, R. L.: Susceptibility to IDDM is marked by MHC supratypes rather than individual alleles. Immunogenetics 22: 643–651, 1985
Kirk, R. L., Sergeantson,S. W., Theophilus, J., Zimmet, P., Whitehouse, S., and Court, J. M.: Age relationship between insulin-dependent diabetes and rare alleles of properdin factor B. Lancet 2: 537, 1979
Maeda, H., Takeuchi, F., Juji, T., Akanuma, Y., Kasuga, M., Lee, Y. S., Kosaga, K., and Tsai, S. H.: HLA-DRw3 in juvenile onset diabetes mellitus in Chinese. Tissue Antigens 15: 173–176, 1980
Maniatis, T., Fritsch, E. F., and Sambrook, J.: Molecular Cloning, a Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1982
O'Neill, G. J., Miniter, P., Pollack, M. S., and Dupont, B.: Different HLA antigen associations for the functionally active and inactive products of the complement C4F1 allele. Hum. Immunol. 1: 23–30, 1980
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, 1983
Southern, E. M.: Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 95: 503–517, 1975
White, P. C., New, M. I., and Dupont, B. E.: HLA-linked congenital adrenal hyperplasia results from a defective gene encoding a cytochrome P-450 specific for steroid 21-hydroxylation. Proc. Natl. Acad. Sci. U.S.A. 81: 7505–7509, 1984
White, P. C., Grossberger, D., Onufer, B. J., Chaplin, D., New, M. I., Dupont, B. E., and Strominger, J. L.: Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man. Proc. Natl. Acad. Sci. U.S.A. 82: 1089–1093, 1985
Wilton, A. N., Christiansen, F. T., and Dawkins, R. L.: Supratype matching improves renal transplant survival. Transplant. Proc. 17: 2211–2216, 1985
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kay, P.H., Martin, E., Dawkins, R.L. et al. Class III gene rearrangements in Thai/Chinese supratypes containing null or defective C4 alleles. Immunogenetics 27, 46–50 (1988). https://doi.org/10.1007/BF00404443
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00404443