After GWAS: mice to the rescue?

Abstract

The genetic basis of human autoimmune diseases remains incompletely understood, despite significant progress from genome-wide association studies (GWAS). In this review we outline how studies in mice may help filling these knowledge gaps. Forward genetic approaches including mutagenesis screens and quantitative trait locus (QTL) mapping studies can identify candidate genes for in depth analysis in human patient populations. Reverse genetic approaches utilize genetically engineered mice to analyze the function of disease-associated genes and their variants. Inbred strains are a distinctive feature of mouse genetics and we discuss their history, advantages and disadvantages. Three factors need to be considered when comparing experimental results from studies in mice and humans: In addition to species-specific differences, phenotypes are affected by the genetic background of the mouse strain being analyzed, and by microbial factors. Despite of these complexities, mice are essential discovery tools in the post GWAS era.