Do alleles in linkage disequilibrium compensate for each other's disadvantageous effects?

When alleles from two different loci behave as independent factors it is possible to calculate the expected frequency of their joint occurrence. In the HLA system significant departures from expected haplotype frequencies occur. Thus antigen B8 occurs together with A1 or/and DR3 in about 95 cases out of 100 (the figure expected by chance is about 45 out of 100). In a similar manner the antigens A3, B7 and DR2 are found associated very much more often than expected by chance alone. The reasons for these observations are obscure, but Fischer (1930) and more recently Bodmer (Bodmer & Bodmer 1978) have argued that some form of natural selection is a major factor in the occurrence and maintenance of linkage disequilibrium. In the present study we show that individual alleles of the common haplotype A1-B8-DR3 can exert different effects as regards IgE levels. This may provide evidence that one of the contributory mechanisms leading to linkage disequilibrium involves selection against individuals having a harmful allele unless it is in association with another conferring compensatory effects.