The genetic control of gamma-globulin heavy chains. Studies of the major heavy chain subgroup utilizing multiple genetic markers.

The genetic control of gammaG1-heavy chains was investigated by taking advantage of two recently described genetic antigens, Gm(z) and Gm(y), both produced by heteroimmunization of rabbits with myeloma proteins. These were studied in conjunction with known genetic markers, Gm(a) and Gm(f). The results indicated that among Caucasians there are two major allelic genes, Gm(za) and Gm(fy), coding for distinct varieties of gammaG1-heavy chains. Each of these contains a pair of genetic antigens which are located on different fragments of the chain and can be separated by enzymatic splitting with papain. The different areas of the heavy chains appear to be under the control of the same gene. In Mongoloid populations a grouping of three genetic antigens, Gm(f), (y), and (a), was found on isolated myeloma proteins and normal gamma-globulins indicating the presence of a Gm(fya) gene. The possible genetic events leading to the contrasting Caucasian and Mongoloid genes are discussed. In the gamma-globulin system the occurrence of multiple genetic antigens in different positions of the same heavy chains is the general rule. A better understanding of the relationships between the genes for the gammaG1-subgroup to those for the gammaG2- and gammaG3-subgroup has been obtained through the use of the multiple genetic markers. Strong evidence was obtained for intergenic crossover mechanisms to explain racial differences in the relationships of these genes as well as certain unusual gene complexes found through family studies. Further evidence was obtained for mapping the closely linked genes for the three subgroups in a specific order.