Characterization of mutants of the vitamin-D-binding protein/group specific component: GC aborigine (1A1) from Australian aborigines and South African blacks, and 2A9 from south Germany.

The structure and organization of the human vitamin-D-binding protein gene (DBP, group-specific component, GC) have recently been determined. Each exon may now be amplified by the PCR method using oligonucleotide primers deduced from the intron sequences near their 5' ends and 3' ends. In this study we examined the anodal GC variants 1A1 and 2A9. Genomic DNA of the variant 1A1 was obtained from Australian Aborigines and from South African Bantu-speaking Blacks. Amplification and sequencing of exon 11 of 1A1 revealed a point mutation in codon 429 at the second position. It is remarkable that this mutation was found in the Australian 1A1 variant and in the African 1A1 variant, and raises the question whether the mutation in these two ethnic groups has a common origin. Genomic DNA of the 2A variant called 2A9 was obtained from South Germany and a point mutation also concerning position 429 in exon 11 was found. The nucleotide exchange in this case, however, was at the first position of the codon. The widely distributed genetic polymorphism of DBP/GC is located in exon 11 and is characterized by substitution at amino acid positions 416 and 420. Variant 1A1 is due to a second site mutation of the allele GC1F; variant 2A9 is due to a mutation in the GC2 allele.