SIMULATION OF THE DISTRIBUTION OF PARENTAL STRAINS GENOMES IN RC STRAINS OF MICE

Recombinant Congenic strains (RC strains) were developed to facilitate mapping of genes influencing complex traits controlled by multiple ge nes. They were produced by inbreeding of the progeny derived fram a se cond backcross from a common 'donor' inbred strain to a common 'backgr ound' inbred strain. Each RC strain contains a random subset of approx imately 12.5% of genes from the donor strain and 87.5% of genes from t he background strain. In this way the genetic control of a complex dis ease may be dissected into its individual components. We simulated the production of the RC strains to study to what extent they have to be characterized in order to obtain sufficient information about the dist ribution of the parental strains' genomes in these strains and to acqu ire insight into parameters influencing their effectiveness in mapping quantitative trait loci (QTLs). The donor strain genome in the RC str ains is fragmented into many segments. Genetic characterization of the se strains with one polymorphic marker per 3.3 centiMorgans (cM) is ne eded to detect 95% of the donor strain genome. The probability of a do nor strain segment being located entirely in between two markers of ba ckground strain origin that are 3 cM apart (and hence escaping detecti on) is 0.003. Although the donor strain genome in the RC strains is sp lit into many segments, the largest part still occurs in relatively lo ng stretches that are mostly concentrated in fewer than 13 autosomes, the median being 9 autosomes. Thus, in mapping QTLs, the use of RC str ains facilitates the detection of linkage.