Analysis of quantitative trait loci that influence animal behavior

Abstract

Behavioral differences between inbred strains of mice and rats have a genetic basis that can now be dissected using quantitative trait locus (QTL) analysis. Over the last 10 years, a large number of genetic loci that influence behavior have been mapped. In this article I review what that information has revealed about the genetic architecture of behavior. I show that most behaviors are influenced by QTL of small effect, each contributing to less than 10% of the variance of a behavioral trait. The small effect of each QTL on behavioral variation suggests that the mutational spectrum is different from that which results in Mendelian disorders. Regions of DNA should be appropriately prioritized to find the molecular variants, for instance by looking at sequences that control the level of gene expression rather than variants in coding regions. While the number of allelic loci that can contribute to a trait is large, this is not necessarily the case: the analysis of selected strains shows that a remarkably small number of QTL can explain the bulk of the genetic variation in behavior. I conclude by arguing that genetic mapping has more to offer than a starting point for positional cloning projects. With advances in multivariate analyses, mapping can also test hypotheses about the psychological processes that give rise to behavioral variation.

Genetic Architecture of Tameness in a Rat Model of Animal Domestication

“…The largest QTL, Tame-1, explains 5.1% of the residual phenotypic variance, while the remaining loci each explain smaller fractions when considered individually. These estimates are in line with the generally small effect sizes reported for QTL for other rodent behaviors (Flint 2003). Across 45 measures and three principal component scores, our study identified 23 significant and 125 suggestive QTL.…”

Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

“…The small effect size of each genetic locus in psychiatric disorders suggests that the causal genetic variations may regulate gene expression levels rather than result in protein coding sequence variation. 25 Hence, examination of cis eSNP associations within the candidate genes is a reliable approach for identification of strong candidate genes for complex traits.…”

QTL Analysis of Multiple Behavioral Measures of Anxiety in Mice

“…We suggest that this may be due to two factors. First is the lower power of these earlier studies, with smaller Ns and genotyping of only extreme behavioral phenotypes, which greatly increases the chances of false negatives (Flint, 2003). Second is the opposing effects of the Ch7 QTL-increased activity in safe areas but substantial suppression of activity in bright areas and open runways-which may counteract each other in some test situations.…”