Quantitative trait locus analysis of aggressive behaviours in mice

Abstract

Quantitative trait locus (QTL) analysis is a forward genetic strategy (phenotype to gene) that enables an investigator to start with a phenotype of interest (e.g. aggressive behaviours), and then identify chromosomal regions (QTLs) and, ultimately, specific gene variants (alleles) within those regions, that influence quantitative variation in the phenotype. QTL analysis is an important complement to reverse genetic strategies (gene to phenotype), such as the generation of knockout and transgenic mice. Although a propensity for aggressive behaviours is partially heritable in mice and other mammals, very few aggression QTLs have been mapped. This slow progress is likely due, in part, to the complexity of aggressive behaviours as phenotypes, which are affected by many nongenetic (environmental and random) factors and gene-environment interactions. This paper reviews the general principles of QTL analysis, as well as the non-genetic factors that can confound aggression QTL studies. Some examples of successfully mapped intermale mouse aggression QTLs are presented, such as QTLs on chromosomes 10 and X. Strategies for fine mapping these loci are discussed, and candidate genes are considered. Finally, newly available mouse genetic resources that may facilitate QTL analysis of aggressive behaviours are suggested, such as consomic mouse strains.