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Received August 1, 2003
Revised September 3, 2003
Accepted after revision November 11, 2003
1 Medical College of Wisconsin
* To whom correspondence should be addressed. E-mail: cowley{at}mcw.edu.
A consomic rat strain is one in which an entire chromosome is introgressed onto the isogenic background of another inbred strain. The chromosome is backcrossed to the parental strain using marker assisted selection. The development and initial physiologic screening of two inbred consomic rat panels (44 strains) on two genetic backgrounds is well underway. These consomic inbred strains provide important advantages in elucidating the relationships of genes to complex biological pathways and disease. First, they provide a means to very rapidly develop a congenic strain over a narrow region. Second, they overcome the problems encountered with segregating crosses where even if linkage is found, each individual in the cross is genetically unique and the combination of genes cannot be reproduced or studied in detail. Genomic substitution approaches (either consomic or congenic) provide greater statistical power to detect linkage than traditional F2 crosses. Third, they also provide sufficient numbers of rats to validate the relationship of the trait that segregated with the markers within the genomic region of interest. Fourth, studies can be performed in a replicative or longitudinal manner to elucidate in greater detail the sequential changes responsible for the observed phenotypes of these animals. Fifth, they enable one to assess the impact of a causal gene region in a genome by allowing comparisons of the effect of replacement of a specific region in a disease susceptible genomic background of vice versa. Sixth, these consomic strains can be used to quickly develop other polygenic models to investigate gene-gene interactions of complex traits or diseases. Finally, they provide the best available inbred control strains for physiological comparisons with the parental strains. Consomic rat strains are proving to be a unique scientific resource that greatly extends our understanding of genes and complex normal and pathological function.
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