Establishment of “The Gene Mine”: a resource for rapid identification of complex trait genes

Abstract

Identification of genes underlying complex traits presents a challenge to which geneticists have responded with many diverse approaches. A common feature of these approaches is that different research groups must, on a case-by-case basis, replicate similar efforts in recruitment, genetic characterization, and analyses. To avoid this expensive "churning," an alternative approach has been proposed: production of an experimental genetic reference population, the Collaborative Cross, in which both genetic diversity and mapping power are maximized. Since this population consists of inbred mouse strains, further advantages are that it is essentially infinitely reproducible; genetic characterization needs to be performed only once; and the founder strains' genomes have been or will be sequenced, allowing imputation of allele sequences of all members of the reference population. Here we describe the establishment of such a genetic reference population, which we dub "The Gene Mine." Over 1000 genetically distinct lines have been established, descended from eight diverse founder strains. Preliminary phenotypic ascertainment of these strains indicates unexpected variability arising from independent assortment of genetic variants. The Gene Mine will be a powerful resource for characterization of essentially any mouse phenotype that has a genetic basis.

Collaborative Cross mice and their power to map host susceptibility toAspergillus fumigatusinfection

“…There are three cohorts of CC mice under construction (Chesler et al 2008;Iraqi et al 2008;Morahan et al 2008). Here we focus on a panel of 120 CC lines at Tel Aviv University (TAU), Israel.…”

The contribution of rodent models to the pathological assessment of flaviviral infections of the central nervous system

“…New developments in mouse biology, such as the Collaborative Cross inbred mouse resource, may provide a rational approach for identifying suitable mouse strains to accurately model infection for flaviviruses that fail to elicit classical disease in existing laboratory rodent lines. Additionally, this resource may enable the discovery of novel combinations of host genes that conspire to elicit disease [109]. Continuing developments in our understanding of mouse biology will serve to foster further discoveries on the genesis of flavivirus pathology and virus-host interactions.…”

Genetic analysis in the Collaborative Cross breeding population

“…Several such panels have been or are being developed for a variety of species, including yeast, Drosophila (Ayroles et al 2009), Arabidopsis (Kover et al 2009), maize (Buckler et al 2009), Caenorhabditis elegans ( Johnson and Wood 1982;Li et al 2006;Rockman and Kruglyak 2009), and mice (Chesler et al 2008;Iraqi et al 2008;Morahan et al 2008). Efforts are also being made to expand (Peirce et al 2004) and maximize the potential of existing populations (Bennett et al 2010).…”