Linkage analysis is the central task in classical genetics. It is essential to constructing maps, investigating the mechanism of recombination, studying relationships among populations, and identifying biologically interesting loci. This work investigates the theoretical bases of linkage mapping, inbreeding, and their application to the mouse. BAYLOC, a Bayesian multilocus genetic mapping algorithm, is developed. BAYLOC assigns probabilities to specific genomic locations for a marker conditional on a data set. BAYLOC's properties are investigated in model calculations. Construction of a map of mouse chromosome 12 from backcross data illustrates BAYLOC's use. The loci are ordered unambiguously and have small, explicit, associated confidence intervals. BAYLOC also allows specification of additional data required to resolve mapping ambiguities. Application of BAYLOC to data culled from different experiments is discussed.
Theoretical arguments and experimental data accounting for inbred mouse strains' extensive genetic variation and supporting their derivation from various wild populations are presented. Computer simulations have been used to investigate the properties of chromosomal segments and the distribution of residual allogenic!ty during Inbreeding. The odds of fixing a chromosomal segment are predicted to be an exponentially decreasing function of its length. Irregular marker spacing significantly alters segment length distribution. Available recombinant inbred strain data for chromosomes 1, 9, and 12 conform to these predictions. The results of these calculations, together with the occurrence of non-domesticus alleles in inbred mice, suggest that segregation of allogenicity introduced by introgression can account for the diversity observed among inbred strains and substrains.
A first attempt to apply these ideas to wild mice is presented. Thirty one mice derived from distinct populations were.examined for polymorphism at seven chromosome 12 loci. The loci were found to display varying amounts of diversity and failed to uncover all alleles encountered in inbred strains. These results show that a larger sample, both in terms of populations surveyed and loci examined, is needed in order to apply analysis of chromosomal segment lengths systematically.