CHARACTERIZATION OF MUTANTS OF THE VITAMIN-D-BINDING PROTEIN GROUP-SPECIFIC COMPONENT - MOLECULAR EVOLUTION OF GC-ASTERISK-1A2 AND GC-ASTERISK-1A3, COMMON IN SOME ASIAN POPULATIONS/

A well defined polymorphism of vitamin D-binding/group-specific compon ent (GC) resides in exon 11. To characterize the molecular basis of GC 1A2 and GC*1A3, common in some Asian populations, we analyzed all cod ing exons amplified by the polymerase chain reaction. GC1F was divide d into GC1F(C) and GC*1F(T) by a C-T transition in the third nucleoti de of the codon (TGC/T) for cysteine(283) in exon 8. The sequencing of exons 8 and 11 showed that GC1A2 and GC*1A3 had occurred on a GC*1F( C) genetic background. They also shared a substitution of cysteine (TG C) for arginine (CGC) at position 429 in exon 11. GC1A2 was character ized by having glycine (GGC) instead of serine (AGC) at position 335 i n exon 9. GC1A2 evolved from GC*1F(T) by three mutational events, i.e . GC1F(T)-->GC*1F(C)-->GC*1A3-->GC*1A2. No evidence was obtained for the existence of the duplicated gene GC1F . 1A2 suggested by isoelect ric focusing (IEF) of serum samples. The idea that the characteristic banding pattern of GC1F . 1A2 after IEF results from partial formatio n of a disulfide bond in the additional cysteine at position 429 is di scussed.