Biochemical Genetics

, Volume 24, Issue 11–12, pp 795–803 | Cite as

DNA sequence evidence for polymorphic forms of human serum amyloid A (SAA)

  • Barbara Kluve-Beckerman
  • George L. Long
  • Merrill D. Benson


Serum amyloid A (SAA) is an acute-phase reactant and precursor to amyloid A protein, the major constituent of the fibril deposits of reactive amyloidosis. The factors determining whether the 104-amino acid SAA molecule is converted into the 76-amino acid amyloid A protein and deposited as fibrils are not known. As an initial step toward investigating the possibility that a particular primary structure of SAA is involved in amyloid formation, we have cloned and determined the nucleotide sequence of human SAA-specific cDNAs. The first clone, selected using an oligonucleotide probe, was shown to encode the signal peptide and amino-terminal region of SAA. The cDNA of this clone served as probe in the selection of two distinct, full-length SAA cDNAs, initially differentiated by the presence (pSAA21) or absence (pSAA82) of a PstI site in the coding sequence. The complete nucleotide sequence of pSAA82 cDNA was determined. Since there appear to be multiple human SAA alleles, it is conceivable that their differential expression is important to amyloid formation.

Key words

serum amyloid A amyloidosis cDNA clone polymorphism 


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  1. Anders, R. F., Natvig, J. B., Sletten, K., Husby, G., and Nordstoga, K. (1977). Amyloid-related serum protein SAA from three animal species: Comparison with human SAA.J. Immunol. 118229.Google Scholar
  2. Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J., and Rutter, W. J. (1979). Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.Biochemistry 185294.Google Scholar
  3. Clewell, D. B., and Helinski, D. R. (1972). Effect of growth conditions on the formation of the relaxation complex of supercoiled ColE1 deoxyribonucleic acid and protein in Escherichia coli.J. Bacteriol. 1101135.Google Scholar
  4. Fung, M. R., Campbell, R. A., and MacGillivray, R. T. A. (1984). Blood coagulation factor X mRNA encodes a single polypeptide chain containing a prepro leader sequence.Nucleic Acids Res. 124481.Google Scholar
  5. Gubler, U., and Hoffman, B. J. (1983). A simple and very efficient method for generating cDNA libraries.Gene 25263.Google Scholar
  6. Hoffman, J. S., and Benditt, E. P. (1982). Changes in high density lipoprotein content following endotoxin administration in the mouse.J. Biol. Chem. 25710510.Google Scholar
  7. Hoffman, J. S., Ericsson, L. H., Eriksen, N., Walsh, K. A., and Benditt, E. P. (1984). Murine tissue amyloid protein AA. NH4-terminal sequence identity with only one of two serum amyloid protein (ApoSAA) gene products.J. Exp. Med. 159641.Google Scholar
  8. Ish-Horowicz, D., and Burke, J. F. (1981). Rapid and efficient cosmid cloning.Nucleic Acids Res. 92989.Google Scholar
  9. Levin, M., Franklin, E. C., Frangione, B., and Pras, M. (1972). The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils.J. Clin. Invest. 512773.Google Scholar
  10. Mandel, M., and Higa, A. (1970). Calcium-dependent bacteriophage DNA infection.J. Mol. Biol. 53157.Google Scholar
  11. Maxam, A. M., and Gilbert, W. (1980). Sequencing end-labeled DNA with base-specific chemical cleavages.Methods Enzymol. 65499.Google Scholar
  12. Morrow, J. F., Stearman, R. S., Peltzman, C. G., and Potter, D. A. (1981). Induction of hepatic synthesis of serum amyloid A protein and actin.Proc. Natl. Acad. Sci. USA 784718.Google Scholar
  13. Moyner, K., Sletten, K., Husby, G., and Natvig, J. B. (1980). An unusually large (83 amino acid residues) amyloid fibril protein AA from a patient with Waldenstrom's macroglobulinaemia and amyloidosis.Scand. J. Immunol. 11549.Google Scholar
  14. Parmelee, D. C., Titani, K., Ericsson, N., Benditt, E. P., and Walsh, K. A. (1982). Amino acid sequence of amyloid-related apoprotein (apoSAA1) from human high-density lipoprotein.Biochemistry 213298.Google Scholar
  15. Rigby, P. W. J., Dieckmann, M., Rhodes, C., and Berg, P. (1977). Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase. I.J. Mol. Biol. 113237.Google Scholar
  16. Roychoudhury, R., Jay, E., and Wu, R. (1976). Terminal labeling and addition of homopolymer tracts to duplex DNA fragments by terminal deoxynucleotidyl transferase.Nucleic Acids Res. 3101.Google Scholar
  17. Sipe, J., Colten, H. R., Goldberger, G., Edge, M. D., Tack, B. F., Cohen, A. S., and Whitehead, A. S. (1985). Human serum amyloid A (SAA): Biosynthesis and postsynthetic processing of preSAA and structural varients defined by complementary DNA.Biochemistry 242931.Google Scholar
  18. Sletten, K., and Husby, G. (1974). The complete amino-acid sequence of nonimmunoglobulin amyloid fibril protein AS in rheumatoid arthritis.Eur. J. Biochem. 41117.Google Scholar
  19. Sletten, K., Marhaug, G., and Husby, G. (1983). The covalent structure of amyloid-related serum protein SAA from two pateints with inflammatory disease.Hoppe-Seyler Z. Physiol. Chem. Bd. 3641039.Google Scholar
  20. Southern, E. (1975). Detection of specific sequences among DNA fragments separated by gel electrophoresis.J. Mol. Biol. 98503.Google Scholar
  21. Yamamoto, K., and Migita, S. (1985). Complete primary structures of two major murine serum amyloid A proteins deduced from cDNA sequences.Proc. Natl. Acad. Sci. 822915.Google Scholar

Copyright information

© Plenum Publishing Corporation 1986

Authors and Affiliations

  • Barbara Kluve-Beckerman
    • 1
  • George L. Long
    • 2
  • Merrill D. Benson
    • 1
  1. 1.Departments of Medicine and Medical Genetics, Rheumatology DivisionIndiana University School of Medicine, Richard L. Roudebush Veterans Administration Medical CenterIndianapolis
  2. 2.Division of Molecular and Cellular BiologyLilly Research LaboratoriesIndianapolis

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