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Linkage relationship between variable and constant region allotypic determinants of human immunoglobulin heavy chains

Abstract

Allotypic (genetic) variations in the variable (V) region of immunoglobulin chains have been extensively studied in the domestic rabbit1–3. The first allotypic determinant identified in the V region of human immunoglobulins, described in our laboratory, is designated Hv(1). Its detection, using protein McE and a rabbit antiserurn to McE, and its mode of inheritance based on family and population studies, have been reported previously4. Briefly, Hv(1) is located in the V region of human immunoglobulin heavy (H) chains of G, M and A classes. It is inherited as an autosomal dominant trait, with a gene frequency in white people of 0.189±0.023. The polymorphic nature of Hv(1) has also been confirmed in black people, studies on a large black kindred (n=80) having confirmed its autosomal dominant mode of inheritance. The gene frequency (determined by the Elston–Stewart method using maximum likelihood5 in blacks is 0.278±0.067. Hv(1) seems analogous to murine idiotypes of the so-called Idx category6 and to rabbit VH-region allotypes in that it is not restricted to any particular immunoglobulin class. This observation is consistent with our previous finding that the same V-region amino acid sequence is able to associate with constant (C) regions of different H-chain classes7. However, an important difference between Hv(1) and the idiotypic markers in mice and rabbits is that the former is presumably associated with the framework residues whereas the latter are associated primarily with the hypervariable regions. We now report results obtained from family studies which indicate absence of linkage between Hv(1) and the human C-region markers Gm (human IgG H chains) and Km (κ-type light chains). These results provide new information about the genetic control of immunoglobulin synthesis in man.

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Pandey, J., Tung, E., Mathur, S. et al. Linkage relationship between variable and constant region allotypic determinants of human immunoglobulin heavy chains. Nature 286, 406–407 (1980). https://doi.org/10.1038/286406a0

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