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Rearrangement of 21-hydroxylase genes in disease-associated MHC supratypes

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Abstract

Human cDNA probes for 21-hydroxylase (21-OH) and for complement component C4 are used on restriction digests of the members of several families with interesting supratypes. The presence of two Taq I fragments of 3.7 kb and 3.2 kb in size with a 21-OH probe is confirmed in most individuals who show no evidence of C4 deletions or 21-OH deficiency. Most individuals also show a doublet of weakly hybridizing bands at approximately 2.5 kb, the smaller of which is part of the 21A gene. The arrangement of the 21-OH genes on disease-associated supratypes was examined, and it is shown that copies of the same supratype from unrelated individuals are usually identical. Evidence is provided for deletions of 21A on the B8, C$AQ0 C4B1, BfS, DR3 and B18, C4A3, C4BQ0, BjF1, DR3 supratypes and a duplication of 21A on the B14, C4A2, C4B1/B2, BfS supratype. Gene rearrangements may be relevant to diseases such as juvenile onset diabetes mellitus.

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References

  • Alper, C. A., Boenisch, T., and Watson, L.: Genetic polymorphism in human glycine-rich beta glycoprotein. J. Exp. Med. 135: 68–80, 1972

    Google Scholar 

  • 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: 3576–3580, 1980

    Google Scholar 

  • Awdeh, Z. L., Raven, D., Yunis, E. J., and Alper, C. A.: Extended HLA-complement-glyoxylase allele haplotypes: Evidence for T/t-like complex in man. Proc. Natl. Acad. Sci. U.S.A. 80: 259–263, 1983

    Google Scholar 

  • 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

    Google Scholar 

  • Carroll, M. C., Belt, T., Palsdottir, A., and Porter, R. R.: Structure and organisation of the C4 genes. Philos. Trans. R. Soc. Lond. (Biol.) 306: 379–388, 1984

    Google Scholar 

  • 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, 1985a

    Google Scholar 

  • 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., in press, 1985b

  • Christiansen, F. T., Dawkins, R. L., Uko, G., McCluskey, J., Kay, P. H., and Zilko, P. J.: Complement allotyping in SLE Association with C4A null. Aust. N. Z. J. Med. 13: 483–488, 1983

    Google Scholar 

  • Cobain, T. J., Stuckey, M. S., McCluskey, J., Wilton, A. N., Gedeon, A., Garlepp, M. J., Christiansen, F. T., Wilson, R. G., and Dawkins, R. L.: The coexistence of IgA deficiency and 21-hydroxylase deficiency marked by specific supratypes. Ann. N. Y. Acad. Sci., 458: 76–84, 1985

    Google Scholar 

  • Dawkins, R. L., Christiansen, F. T., Kay, P. H., Garlepp, M., McCluskey, J., Hollingsworth, P. N., and Zilko P. J.: Disease associations with complotypes, supratypes and haplotypes. Immunol. Rev. 70: 5–22, 1983

    Google Scholar 

  • Dupont, B., Pollack, M. S., Levine, L. S., O'Neill, G. J., Hawkins, B., and New, M. I.: Congenital adrenal hyperplasia and HLA: Joint report from the Eighth Histocompatibility Workshop. In P.I. Terasaki (ed.): Histocompatibility Testing 1980, pp. 693–706, UCLA Tissue Typing Laboratory, Los Angeles, 1980

    Google Scholar 

  • Maniatis, T., Fritsch, E. F., and Sambrook, J.: Molecular Cloning, a Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1982

    Google Scholar 

  • McCluskey, J., Kay, P. H., Dawkins, R. L., Komori, K., Christiansen, F. T., and McCann, V. J.: Association of specific MHC supratypes with rheumatoid arthritis and insulin dependent diabetes mellitus. Disease Markers 1: 197–212, 1983

    Google Scholar 

  • Raum, D., Awdeh, Z., Yunis, E. J., Alper, C. A., and Gabbay, K. H.: Extended major histocompatibility complex haplotypes in type I diabetes mellitus. J. Clin. Immunol. 74: 449–454, 1984

    Google Scholar 

  • Scholz, S., Holler, W., Krom, D., Bidlingmeier, F., Zanden, H., and Albert, E. D.: Three different HLA associations in the three types of 21-hydroxylase congenital adrenal hyperplasia. In E. D. Albert, M. P. Baur, and W. R. Mayr (eds.): Histocompatibility Testing 1984, pp. 658–658, Springer-Verlag, Berlin, 1984

    Google Scholar 

  • Southern, E. M.: Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 95: 503–517, 1975

    Google Scholar 

  • Terasaki, P. I. (ed.): Histocompatibility Testing 1980, UCLA Tissue Typing Laboratory, Los Angeles, 1980

    Google Scholar 

  • 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. Nutl. Acad. Sci. U.S.A. 81: 7505–7509, 1984

    Google Scholar 

  • White, P. C., Grossberger, D., Onufer, B. J., Chaplin, D., New, M. I., Dupont, B., 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

    Google Scholar 

  • Wilton, A. N., Cobain, T. J., and Dawkins, R. L.: Family studies of IgA deficiency. Immunogenetics 21: 333–342, 1985

    Google Scholar 

  • Zilko, P. J., Dawkins, R. L., Holmes, K., and Witt, C.: Genetic control of suppressor lymphocyte function in myasthenia gravis: Relationship of impaired suppressor function to HLA-B8/DRw3 and cold reactive lymphocytotoxic antibodies. Clin. Immunol. Immunopathol. 14: 222–230, 1979

    Google Scholar 

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Publication Q8549 of the Departments of Clinical Immunology, Royal Perth Hospital and The Queen Elizabeth II Medical Centre, Perth, Western Australia

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Garlepp, M.J., Wilton, A.N., Dawkins, R.L. et al. Rearrangement of 21-hydroxylase genes in disease-associated MHC supratypes. Immunogenetics 23, 100–105 (1986). https://doi.org/10.1007/BF00377968

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