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. 1968 Oct 1;128(4):763–784. doi: 10.1084/jem.128.4.763

FURTHER STUDIES ON THE γG-HEAVY CHAIN GENE COMPLEXES, WITH PARTICULAR REFERENCE TO THE GENETIC MARKERS Gm(g) AND Gm(n)

J B Natvig 1, H G Kunkel 1, W J Yount 1, J C Nielsen 1
PMCID: PMC2138545  PMID: 19867305

Abstract

The recently described Gm (g) and Gm (n) genetic markers of the γG3- and γG2-subgroups of γ-globulin were characterized in detail primarily through studies of myeloma proteins, their polypeptide chains and fragments. Antisera derived from rabbits, non-human primates and rheumatoid arthritis patients gave identical results. This contrasted with the Gm (b) system where the rabbit antisera react with a different genetic determinant (b0) than the sera from rheumatoid arthritis patients (b). The Gm (g) and Gm (n) antigens were detected both by precipitin analysis and by hemagglutination inhibition. The Gm (g) antigen was not associated with any of the other genetic antigens of the γG3-proteins which all belonged in the Gm (b) class. The genes for the latter were always allelic to the gene coding for Gm (g), with that for Gm (b0) constantly present when that for Gm (g) was absent. The Gm (g) and Gm (n) markers were of particular value in tracing the various gene complexes made up of the closely linked subgroup genes. Further support was gained for the concept that the different gene complexes of various population groups arose primarily through crossing-over. The Gm g and Gm b genes for the γG3-subgroup were extremely closely linked to those for the γG1-subgroup. However the Gm (n) marker indicated that the γG2-subgroup genes were probably further separated on the chromosome. Additional evidence was obtained for the γG2-γG3-γG1-order of the subgroup cistrons. Among the wide range of gene complexes a new type (γG2,—,γ/G1) was described. This complex appeared to have a deletion of the γG3-cistron. Lower levels of γG3-globulin were found in the sera of the individuals with this gene in the heterozygous state. The possibility that this unusual complex arose through an unequal nonhomologous crossing-over is discussed.

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Selected References

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  1. Frangione B., Franklin E. C., Fudenberg H. H., Koshland M. E. Structural studies of human gamma-G-myeloma proteins of different antigenic subgroups and genetic specificities. J Exp Med. 1966 Oct 1;124(4):715–732. doi: 10.1084/jem.124.4.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. GREY H. M., MANNIK M., KUNKEL H. G. INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS. CHARACTERISTICS AND LOCALIZATION TO SUBUNITS. J Exp Med. 1965 Apr 1;121:561–575. doi: 10.1084/jem.121.4.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Grey H. M., Kunkel H. G. Heavy-chain subclasses of human gamma-G-globulin. Peptide and immunochemical relationships. Biochemistry. 1967 Aug;6(8):2326–2334. doi: 10.1021/bi00860a007. [DOI] [PubMed] [Google Scholar]
  4. HARBOE M. A new hemagglutinating substance in the Gm system, anti-Gmb. Acta Pathol Microbiol Scand. 1959;47:191–198. doi: 10.1111/j.1699-0463.1959.tb04848.x. [DOI] [PubMed] [Google Scholar]
  5. Henningsen K. Exceptional MNSs- and Gm-types within a Danish family causal relationship or coincidence? Acta Genet Stat Med. 1966;16(3):239–241. doi: 10.1159/000151968. [DOI] [PubMed] [Google Scholar]
  6. Hilschmann N., Craig L. C. Amino acid sequence studies with Bence-Jones proteins. Proc Natl Acad Sci U S A. 1965 Jun;53(6):1403–1409. doi: 10.1073/pnas.53.6.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. KUNKEL H. G., ALLEN J. C., GREY H. M., MARTENSSON L., GRUBB R. A RELATIONSHIP BETWEEN THE H CHAIN GROUPS OF 7S GAMMA-GLOBULIN AND THE GM SYSTEM. Nature. 1964 Jul 25;203:413–414. doi: 10.1038/203413a0. [DOI] [PubMed] [Google Scholar]
  8. Kunkel H. G., Yount W. J., Litwin S. D. Genetically determined antigen of the Ne subgroup of gamma-globulin: detection by precipitin analysis. Science. 1966 Nov 25;154(3752):1041–1043. doi: 10.1126/science.154.3752.1041. [DOI] [PubMed] [Google Scholar]
  9. Litwin S. D., Kunkel H. G. Genetic factors of human gamma globulin detected by rabbit antisera. Transfusion. 1966 Mar-Apr;6(2):140–145. doi: 10.1111/j.1537-2995.1966.tb04712.x. [DOI] [PubMed] [Google Scholar]
  10. Litwin S. D., Kunkel H. G. The genetic control of gamma-globulin heavy chains. Studies of the major heavy chain subgroup utilizing multiple genetic markers. J Exp Med. 1967 May 1;125(5):847–862. doi: 10.1084/jem.125.5.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mårtensson L. Genes and immunoglobulins. Vox Sang. 1966 Sep-Oct;11(5):521–545. doi: 10.1111/j.1423-0410.1966.tb04251.x. [DOI] [PubMed] [Google Scholar]
  12. Mårtensson L., Kunkel H. G. Distribution among the gamma-globulin molecules of different genetically determined antigenic specificities in the Gm system. J Exp Med. 1965 Oct 1;122(4):799–811. doi: 10.1084/jem.122.4.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mårtensson L., van Loghem E., Matsumoto H., Nielsen J. Gm(s) and Gm(t): genetic determinants of human gamma-globulin. Vox Sang. 1966 Jul-Aug;11(4):393–418. doi: 10.1111/j.1423-0410.1966.tb04237.x. [DOI] [PubMed] [Google Scholar]
  14. Müller-Eberhard H. J. Chemistry and reaction mechanisms of complement. Adv Immunol. 1968;8:1–80. doi: 10.1016/s0065-2776(08)60464-2. [DOI] [PubMed] [Google Scholar]
  15. Natvig J. B. Gm(g)--a "new" gamma-globulin factor. Nature. 1966 Jul 16;211(5046):318–319. doi: 10.1038/211318a0. [DOI] [PubMed] [Google Scholar]
  16. Natvig J. B. Heterogeneity of anti-gamma-globulin factors detected by pepsin-digested human gamma G-globulin. Acta Pathol Microbiol Scand. 1966;66(3):369–382. doi: 10.1111/apm.1966.66.3.369. [DOI] [PubMed] [Google Scholar]
  17. Natvig J. B. Incomplete anti-D antibody with changed Gm specificity. Acta Pathol Microbiol Scand. 1965;65(3):467–479. doi: 10.1111/apm.1965.65.3.467. [DOI] [PubMed] [Google Scholar]
  18. Natvig J. B. Specificity of human anti-gamma-globulin factors for heavy chain subgroup determinants and autologous gamma-globulin fragments. Bibl Haematol. 1968;29:313–317. doi: 10.1159/000384626. [DOI] [PubMed] [Google Scholar]
  19. PORTER R. R. The hydrolysis of rabbit y-globulin and antibodies with crystalline papain. Biochem J. 1959 Sep;73:119–126. doi: 10.1042/bj0730119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Prahl J. W. The C-terminal sequences of the heavy chains of human immunoglobulin G myeloma proteins of differing isotopes and allotypes. Biochem J. 1967 Dec;105(3):1019–1028. doi: 10.1042/bj1051019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. ROPARTZ C., RIVAT L., ROUSSEAU P. Y. LE GM(B) ET SES PROBL'EMES. Vox Sang. 1963 Nov-Dec;8:717–723. doi: 10.1111/j.1423-0410.1963.tb02378.x. [DOI] [PubMed] [Google Scholar]
  22. Ropartz C., Rivat L., Rousseau P. Y. Conception actuelle de la génétique du système Gm. Une famille caucasienne permettant de supposer l'existence de la rare combinaison génique Gm4,21,22. Rev Fr Etud Clin Biol. 1967 Feb;12(2):185–188. [PubMed] [Google Scholar]
  23. STEINBERG A. G., GOLDBLUM R. A GENETIC STUDY OF THE ANTIGENS ASSOCIATED WITH THE GM(B) FACTOR OF HUMAN GAMMA GLOBULIN. Am J Hum Genet. 1965 Mar;17:133–147. [PMC free article] [PubMed] [Google Scholar]
  24. Terry W. D., Fahley J. L., Steinberg A. G. GM and INV factors in subclasses of human IgG. J Exp Med. 1965 Dec 1;122(6):1087–1102. doi: 10.1084/jem.122.6.1087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Thorpe N. O., Deutsch H. F. Studies on papain produced subunits of human gamma-G-globulins. II. Structures of peptides related to the genetic Gm activity of gamma-G-globulin Fc-fragments. Immunochemistry. 1966 Jul;3(4):329–337. [PubMed] [Google Scholar]
  26. Watts R. L., Watts D. C. Gene duplication and the evolution of enzymes. Nature. 1968 Mar 23;217(5134):1125–1130. doi: 10.1038/2171125a0. [DOI] [PubMed] [Google Scholar]
  27. Yount W. J., Kunkel H. G., Litwin S. D. Studies of the Vi (gamma-2c) subgroup of gamma-globulin. A relationship between concentration and genetic type among normal individuals. J Exp Med. 1967 Jan 1;125(1):177–190. doi: 10.1084/jem.125.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. van Loghem E., Mårtensson L. Genetic (Gm) determinants of the gamma-2c (Vi) subclass of human IgG immunoglobulins. A study with special reference to Gm(c3) and Gm(c5), and their relationship with the Gm(b) determinants. Vox Sang. 1967 Nov;13(5):369–392. doi: 10.1111/j.1423-0410.1967.tb03782.x. [DOI] [PubMed] [Google Scholar]

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