Dissection of Host Susceptibility to Bacterial Infections and Its Toxins

Methods Mol Biol. 2017:1488:551-578. doi: 10.1007/978-1-4939-6427-7_27.

Abstract

Infection is one of the leading causes of human mortality and morbidity. Exposure to microbial agents is obviously required. However, also non-microbial environmental and host factors play a key role in the onset, development and outcome of infectious disease, resulting in large of clinical variability between individuals in a population infected with the same microbe. Controlled and standardized investigations of the genetics of susceptibility to infectious disease are almost impossible to perform in humans whereas mouse models allow application of powerful genomic techniques to identify and validate causative genes underlying human diseases with complex etiologies. Most of current animal models used in complex traits diseases genetic mapping have limited genetic diversity. This limitation impedes the ability to create incorporated network using genetic interactions, epigenetics, environmental factors, microbiota, and other phenotypes. A novel mouse genetic reference population for high-resolution mapping and subsequently identifying genes underlying the QTL, namely the Collaborative Cross (CC) mouse genetic reference population (GRP) was recently developed. In this chapter, we discuss a variety of approaches using CC mice for mapping genes underlying quantitative trait loci (QTL) to dissect the host response to polygenic traits, including infectious disease caused by bacterial agents and its toxins.

Keywords: Bacterial infections; Collaborative Cross mice; Heritability; Host response; QTL and fine mapping; Recombinant inbred lines.

MeSH terms

  • Animals
  • Bacterial Infections / etiology*
  • Bacterial Infections / metabolism*
  • Bacterial Infections / mortality
  • Bacterial Toxins / metabolism*
  • Chromosome Mapping
  • Crosses, Genetic
  • Disease Models, Animal
  • Disease Susceptibility*
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Host-Pathogen Interactions / genetics*
  • Mice
  • Mice, Inbred Strains
  • Phenotype
  • Quantitative Trait Loci

Substances

  • Bacterial Toxins