Detection of genetic variation with radioactive ligands. II. Genetic variants of vitamin D-labeled group-specific component (Gc) proteins.

A novel technique for detecting electrophoretic and quantitative variants of group-specific component (Gc) proteins is described. The technique, in vitro labeling with radioactive vitamin D followed by polyacrylamide gel electrophoresis and autoradiography (PAGE autoradiography), permits sensitive, high resolution detection of Gc variants by virtue of a physiologically significant property: the ability of Gc to bind vitamin D and 25-hydroxyvitamin D. Using this procedure, anodal Gc variants, with mobility similar to Gc Aborigine and Gc Eskimo, were observed in Chinese, Japanese, African Pygmies, and American Blacks. The gene frequency of these variants ranges from 2.6% to 15%; they were not previously known to be polymorphic in these populations. In addition to qualitative variants, individual variation in Gc band density ratios is documented and discussed. These studies not only illustrate the utility of PAGE autoradiography in screening Gc, but also confirm that a major functional role of Gc in man and other animals is the transport of vitamin D and vitamin D metabolites.