2 - Application of genetic epidemiology to dissecting host susceptibility/resistance to infection illustrated with the study of common mycobacterial infections

Summary

INTRODUCTION

In the general context of genetic dissection of complex traits, genetics of human infectious diseases present the following several advantages and specificities: (1) there is a known causative agent which is absolutely required to become infected and to get the disease, but generally not sufficient stressing the importance of the host background; (2) environmental factors influencing the risk of infection are generally known and can be taken into account in the analysis when they are accurately measured; (3) there is a strong orientation in the choice of candidate genes based on the function of the gene and its known role in the response to the studied pathogen and/or on mouse–human chromosome homology exploiting the identification of murine resistance loci; and (4) the identification of major genes involved in the response to a given infectious pathogen takes advantage of the opportunity to study several complementary traits related to this pathogen. Among these traits are clinical phenotypes which are usually binary (affected/unaffected) but can take into account time to onset of the disease (e.g., time of progression to AIDS for HIV-infected patients), biological phenotypes measuring infection which can be either quantitative (e.g., infection intensities measured by fecal egg counts in schistosomiasis) or binary (HIV seropositive/seronegative), and immunological phenotypes measuring the immune response (antibody or cytokine levels, skin test response, etc.) more or less specific to a given antigen.