Comparison of the hinge-coding segments in human immunoglobulin gamma heavy chain genes and the linkage of the gamma 2 and gamma 4 subclass genes.

The genes for the human immunoglobulin heavy chain constant region subclasses have been examined in clones isolated from a phage library containing human genomic DNA. Nucleotide sequencing and restriction enzyme mapping show that the CH1, hinge, CH2, and CH3 domains are present as distinct genetic elements separated by short intervening sequences in these genes: the gamma 3 gene is unique amongst these genes in that it possesses four separate hinge-coding segments. A further gamma gene has been identified which does not correspond to a known human gamma protein: this gene contains a hinge related to the first hinge of the gamma 3 gene and may represent an inactive or pseudo gamma gene. Comparison of a number of overlapping clones containing gamma 2 and gamma 4 genes shows that they are separated in human DNA by approximately 19 kb and that the gamma 2 gene is located upstream of gamma 4. Both genes (order 5'C gamma 2-C gamma 4-3') are orientated in the same direction of transcription.