Restriction fragment length polymorphisms associated with immunoglobulin C gamma genes reveal linkage disequilibrium...

We have demonstrated that restriction fragment length polymorphisms (RFLPs) produced by BamHI can be used as markers for constant (C) region heavy chain genes C psi gamma (C gamma pseudogene), C gamma 2, and C gamma 4. These RFLPs were found nonrandomly associated in the population sample studied. Of the eight combinations (haplotypes) of RFLPs theoretically possible, only two accounted for a total of 88% of the 116 chromosomes examined, a value greater than the total of 25% expected from random segregation of alleles. This indicates considerable linkage disequilibrium between C psi gamma, C gamma 2, and C gamma 4. Quantitative assessment of the degree of association between C gamma gene RFLPs, Gm markers, and switch region RFLPs adjacent to C mu and C alpha 1 revealed that C psi gamma is most tightly associated with C gamma 2 (r = 0.81 and 0.95 for the two common haplotypes), suggesting that C psi gamma maps to a position lying between C alpha 1 and C gamma 2. The association analysis used here should have general applicability for studying the genomic organization of other multigene families.