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Linkage disequilibrium between amino acid sites in immunoglobulin genes and other multigene families.

Linkage disequilibrium between segregating amino acid sites in repeated genes which form a multigene family was investigated by using the population genetics theory. The degree of non-random association of amino acids is measured by the disequilibrium coefficient which is determined by the balance among various forces; unequal and equal crossing-over, mutation, random genetic drift and recombination which takes place between the two sites in question. Another measure of disequilibrium, ‘standardized identity excess’, represents excess probability of simultaneous identity at the two sites over that expected from random association of amino acids. Sequence data of variable region of immunoglobulins provide most interesting example of multigene family to apply the theory. Statistical analyses on identity excess for various groups and subgroups of variable region sequences of immunoglobulins suggest that a multigene family such as human κ or mouse κ gene family consists of several subfamilies between which recombination is limited. The analyses also indicate that the recombination may take place between any gene members in one subfamily.