Genome-tagged mice (GTM): Two sets of genome-wide congenic strains

An important approach for understanding complex disease risk using the mous e is to map and ultimately identify the genes conferring risk. Genes contri buting to complex traits can be mapped to chromosomal regions using genome scans of large mouse crosses. Congenic strains can then be developed to fin e-map a trait and to ascertain the magnitude of the genotype effect in a ch romosomal region, Congenic strains are constructed by repeated backcrossing to the background strain with selection at each generation for the presenc e of a donor chromosomal region, a time-consuming process, One approach to accelerate this process is to construct a library of congenic strains encom passing the entire genome of one strain on the background of the other, We have employed marker-assisted breeding to construct two sets of overlapping congenic strains, called genome-tagged mice (GTMs), that span the entire m ouse genome. Both congenic GTM sets contain more than 60 mouse strains, eac h with on average a 23-cM introgressed segment (range 8 to 58 cM). C57BL/6J was utilized as a background strain for both GTM sets with either DBA/2J o r CAST/Ei as the donor strain. The background and donor strains are genetic ally and phenotypically divergent. This genetic basis for the phenotypic st rain differences can be rapidly mapped by simply screening the GTM strains. Furthermore, the phenotype differences can be fine-mapped by crossing appr opriate congenic mice to the background strain, and complex gene interactio ns can be investigated using combinations of these congenics. (C) 2001 Acad emic Press.