The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 128, 763-784, Copyright © 1968 by The Rockefeller University Press

ARTICLE

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

J. B. Natvig M.D.1, H. G. Kunkel M.D.1, W. J. Yount M.D.1, and J. C. Nielsen M.D.1

1 From The Rockefeller University, New York 10021, and the University Institute of Forensic Medicine, Copenhagen, Denmark

The recently described Gm (g) and Gm (n) genetic markers of the gammaG3- and gammaG2-subgroups of gamma-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 gammaG3-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 Gmg and Gmb genes for the gammaG3-subgroup were extremely closely linked to those for the gammaG1-subgroup. However the Gm (n) marker indicated that the gammaG2-subgroup genes were probably further separated on the chromosome. Additional evidence was obtained for the gammaG2-gammaG3-gammaG1-order of the subgroup cistrons.

Among the wide range of gene complexes a new type (gammaG2,—,gamma/G1) was described. This complex appeared to have a deletion of the gammaG3-cistron. Lower levels of gammaG3-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.

 Submitted on June 7, 1968


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