The unfolding story of genes encoding variant
glycophorin molecules is already known to be more complicated than described here. The principles outlined provide a basis for understanding the fundamental events that occur in genes encoding the
glycophorins as well as genes encoding unrelated
proteins carrying other
blood group antigens. Over 20 different genes involving the GYPA and GYPB family have been described. These genes arise from gene rearrangements within a relatively short region. This hot spot of activity has inverted palindromic sequences, which are known to be sites for
DNA recombination. Similar structures exist in the major histocompatibility complex (MHC) where allelic diversity is a functional requisite. However, the significance of allelic diversity in the
glycophorin gene family is not understood. The GYPA, GYPB and GYPE gene cluster is known to be prone to mutation by radiation because there is a high incidence of somatic mutation events in atomic bomb survivors, in people exposed to accidental radiation, in patients with
Bloom's syndrome and in patients receiving
radiation therapy. The mutation events were dose dependent: the greater the exposure, the greater proportion of red blood cells exhibited mutations. While it is known that MHC diversity protects against
infection, the reason for
glycophorin rearrangements remains to be determined.