Understanding mammalian genetic systems: the challenge of phenotyping in the mouse

Abstract

Understanding mammalian genetic systems is predicated on the determination of the relationship between genetic variation and phenotype. Several international programmes are under way to deliver mutations in every gene in the mouse genome. The challenge for mouse geneticists is to develop approaches that will provide comprehensive phenotype datasets for these mouse mutant libraries. Several factors are critical to success in this endeavour. It will be important to catalogue assay and environment and where possible to adopt standardised procedures for phenotyping tests along with common environmental conditions to ensure comparable datasets of phenotypes. Moreover, the scale of the task underlines the need to invest in technological development improving both the speed and cost of phenotyping platforms. In addition, it will be necessary to develop new informatics standards that capture the phenotype assay as well as other factors, genetic and environmental, that impinge upon phenotype outcome.

Figure 1. Phenotype Data Is a Complex Three-Dimensional Matrix of Information Comprising Phenotype Outputs from a Large Number of Tests on Individual Mutants in Defined Genetic Backgrounds under Specific Environmental Conditions

Figure 2. Examples of New Phenotyping Platforms and Imaging Approaches Which Are Beginning to Be Applied, or Being Considered, for High Throughput Mouse Phenotype Screens on a Large Number of Mutant Animals

The table is not comprehensive but provides exemplars of tests where technological developments are providing improvements in speed and cost that will enable their utilisation in broad primary screens of mouse mutants. Note that there is increasingly the potential for generic molecular phenotyping approaches such as gene expression and protein arrays that impact upon multiple phenotyping domains to be applied as primary screens.