A consomic strain is an inbred strain with one of its chromosomes replaced by the homologous chromosome of another inbred strain via a series of marker-assisted backcrosses. A complete panel of consomics consists of 21 strains, each derived from the same donor and host but having a different chromosome (Chr 1-19, X or Y) of the host replaced by its counterpart from the donor. A strain is regarded as fully consomic after 10 generations of backcrossing (including the initial cross). However, when constructing consomics that carry autosomes or the X Chromosome from the donor strain, the progeny must be genotyped at every backcross generation to ensure that recombination has not occurred between the donor chromosome and its host counterpart. Traditionally, the Y Chromosome has been transferred onto a new strain background without genotyping. However, if DNA markers are known in the pseudoautosomal region, they may be genotyped.
ApplicationsAnalysis of a consomic panel allows a researcher to rapidly associate a phenotype with a particular chromosome for which the donor and host differ. Consomics exhibiting the trait of interest can be used to produce, within a few generations, a series of congenic strains that subdivide the chromosome into segments and thus refine the position of the causative locus. This is achieved by backcrossing to mice of the host strain, identifying recombinant progeny, and determining which regions of the chromosome are associated with the phenotype. Furthermore, if two or more genes on the same chromosome interact to influence a phenotype, these additive or epistatic allele combinations can be detected in the consomic strain bearing the donor chromosome of interest and can be separated in the congenic strains thus generated. Consomics can also be used to confirm weak quantitative trait loci identified in linkage crosses. In addition, they can be used to identify modifier genes affecting the phenotypic expression of spontaneous or induced mutations simply by crossing mutant mice to mice of the consomic strain panel.
Consomic panels are powerful tools for analyzing complex traits that are polymorphic between inbred mouse strains. Using a consomic panel can accelerate QTL identification and mapping of traits that differ from its progenitor strains. Detecting a QTL is accomplished simply by phenotyping mice from each member of the set. The presence of the trait of interest in a particular consomic indicates that there must be at least one QTL on that chromosome. This approach has many advantages (and few disadvantages) over traditional QTL mapping.
A consomic set is a perpetually renewable resource because each strain in a set is genetically stable.
Phenotypic data acquired for a consomic set are both cumulative and comparable, enhancing the value of the strain set for further studies.
Initial linkage crosses are unnecessary.
Genotyping is not required. Detection of a QTL associated with a phenotypic trait that differs between the donor and the host of a Consomic panel is accomplished by phenotyping mice from each member of the set. The presence of the trait of interest in a particular Consomic indicates that there must be at least one QTL on that chromosome.
Due to epistatic effects, consomics from progenitors with phenotypes that do not differ significantly may also be informative, especially for complex traits dependent on multiple genes.
Once a QTL is identified on a particular chromosome, the appropriate consomic can quickly be backcrossed to the host strain, and progeny with recombinations in the donor chromosome can be identified. Using this method, the location of a QTL can be finely resolved.
- QTLs with weak phenotypic effects can be examined in the light of results from linkage crosses.
Initially, QTLs are localized to an entire chromosome rather than to a chromosomal region (as in segregating crosses, recombinant inbred strains, and recombinant congenic strains).
Initial QTLs identified in consomics do not discriminate between single and multiple QTLs.
- Currently, only two consomic panels are readily available, limiting the use of consomics for analyzing complex traits found in other strains.
Consomics are designated, without intervening spaces, by the full strain name of the host strain, a hyphen, the abbreviation for “chromosome” and an Arabic number denoting the transferred donor chromosome, the superscripted donor strain symbol, a forward slash, the ILAR-assigned Registration Code of the scientist who produced the strain, and the Registration Code for the laboratory that maintains and distributes the strain. For example, C57BL/6J-Chr1A/NaJ carries Chr 1 from strain A/J (A) on a C57BL/6J background, was constructed in the laboratory of Joseph Nadeau (Na), and is maintained at The Jackson Laboratory (J).
Tips on Care and Handling
A consomic that carries an autosome or the X Chromosome from the donor strain is maintained as an inbred colony by sibling (sister x brother) mating. A consomic carrying the Y chromosome of the donor strain is maintained by crossing male carriers to females of the host strain. In general, consomics require no special husbandry.
Additional information on consomic strains may be found in The Jackson Laboratory’s
“Macroarray Resource Manual,” obtainable free by completing this literature request form.
Nadeau JH, Singer JB, Matin A, Lander ES. 2000. Analysing complex genetic traits with chromosome substitution strains. Nat Genet 24:221-5.
Singer JB, Hill AE, Burrage LC, Olszens KR, Song J, Justice M, O'Brien WE, Conti DV, Witte JS, Lander ES, Nadeau JH. 2004. Genetic dissection of complex traits with chromosome substitution strains of mice. Science 304:445-8.