Use of Congenic Mouse Strains for Candidate Disease Gene Identification in Complex Traits

Abstract

Genetic analysis aims to establish the relationship between a gene and a specific trait through the parallel study of phenotype and underlying genetic variation. Current tools for genetic analysis in the mouse extend from standard matings such as intercrosses and backcrosses to the use of more specialized resources such as recombinant inbred (RI) strains and recombinant congenic (RC) strains. Both RI and RC strains are characterized by the fixation of a genome-wide admixture of novel genetic combinations subsequent to meiotic recombination and segregation. Other resources of particular interest for the analysis of complex traits include consomic and congenic strains. In consomic or chromosome substitution strains, the genetic admixture is restricted to a single chromosome, and in congenic strains it is restricted to a single chromosomal region. Consomic and congenic mouse stocks have played a pivotal role in the genetic analysis of complex diseases that are often under the control of both environmental and multiple genetic factors and include type 1 diabetes, multiple sclerosis, obesity, and cancer. This chapter will provide an overview of the different tools available in the mouse for the genetic analysis of complex traits, with particular emphasis on different aspects of the use of congenic mouse strains.