Strong allelic selection in the course of brother x sister matings in mice

A set of 36 recombinant congenic mouse strains, resulting from crosses between B10.D2 and DBA/2, was created. During the backcross phase, animals were selected for their sensitivity to the graft-versus-host reaction induced by a B10.D2 hematopoietic cell transplant after irradiation. The progress of inbreeding was followed throughout the brother x sister phase by determining the allelic form of 14 genetic markers. During the backcross phase, the mean selective value per generation and per marker for the heterozygous allelic combination was 2.81 (1 for the homozygous B10.D2). During the brother x sister phase, this value was 1.15 and 0.30 for the heterozygous and the DBA/2 homozygous combinations, respectively (1 for the homozygous B10.D2). The origin of this strong allelic disadvantage for the DBA/2 homozygote, in the face of countervailing selection, is discussed. These data strongly suggest coadaptation between alleles constituting the genome of the inbred strains of the laboratory mouse, resulting in strong counterselection of the alleles derived from one inbred strain when a small amount is spread over the genetic background of another inbred strain.