AUTHOR=Kause Antti , Ødegård Jørgen TITLE=The genetic analysis of tolerance to infections: a review JOURNAL=Frontiers in Genetics VOLUME=3 YEAR=2012 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2012.00262 DOI=10.3389/fgene.2012.00262 ISSN=1664-8021 ABSTRACT=

Tolerance to infections is defined as the ability of a host to limit the impact of a given pathogen burden on host performance. Uncoupling resistance and tolerance is a challenge, and there is a need to be able to separate them using specific trait recording or statistical methods. We present three statistical methods that can be used to investigate genetics of tolerance-related traits. Firstly, using random regressions, tolerance can be analyzed as a reaction norm slope in which host performance (y-axis) is regressed against an increasing pathogen burden (x-axis). Genetic variance in tolerance slopes is the genetic variance for tolerance. Variation in tolerance can induce genotype re-ranking and changes in genetic and phenotypic variation in host performance along the pathogen burden trajectory, contributing to environment-dependent genetic responses to selection. Such genotype-by-environment interactions can be quantified by combining random regressions and covariance functions. To apply random regressions, pathogen burden of individuals needs to be recorded. Secondly, when pathogen burden is not recorded, the cure model for time-until-death data allows separating two traits, susceptibility and endurance. Susceptibility is whether or not an individual was susceptible to an infection, whereas endurance denotes how long time it took until the infection killed a susceptible animal (influenced by tolerance). Thirdly, the normal mixture model can be used to classify continuously distributed host performance, such as growth rate, into different sub-classes (e.g., non-infected and infected), which allows estimation of host performance reduction specific to infected individuals. Moreover, genetics of host performance can be analyzed separately in healthy and affected animals, even in the absence of pathogen burden and survival data. These methods provide novel tools to increase our understanding on the impact of parasites, pathogens, and production diseases on host traits.