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Every “infective disease” (the term is Garrod’s) has two components: the susceptibility of the host and the virulence of the pathogen. Infection is a contest between two genomes, expressed in two competing organisms. This chapter addresses various examples of host susceptibility and resistance to infectious agents, illustrated by examples such as the hemoglobin variants, G6PD deficiency, malaria, mycobacterial diseases, HIV and AIDS, and hepatitis.


It has been recognized since ancient times that people vary in their susceptibility to infectious diseases and before the relevant microbe was identified some such diseases were regarded as familial.1 Earlier in this century, twin studies began to provide some estimates of the magnitude of the host genetic component to variable susceptibility. It is now clear that genetic variation in the host has a substantial influence on the course of disease caused by many infectious microorganisms. Such interactions have been particularly well studied in human infectious diseases where both the pathogen and the host genome are well characterized.

Over the last 10 years, the methodologies available for analyzing human genetic variation have advanced rapidly, leading to the identification of a large number of genes associated with altered susceptibility to infectious pathogens. However, it is likely that those characterized so far represent only a small fraction of a very large number of genes that influence susceptibility to one or other infection. Indeed susceptibility to most infectious diseases in humans is likely to be highly polygenic, and this has both attractions and disadvantages for those attempting to identify relevant genes. A large number of genes increases the probability of success with a candidate-gene approach but makes it more difficult to map genes by linkage analysis of multicase families. Another complicating factor in attempts to identify infectious disease susceptibility genes is genetic variation in the infectious pathogen. Nonetheless, a surprising amount of progress has been made in identifying susceptibility and resistance genes, and this is providing new insights into disease pathogenesis and resistance mechanisms. Conversely, it appears increasingly likely that a substantial proportion of the functional variation in the human genome has evolved to facilitate defense against infectious pathogens, leading to the observed polygenic variation in susceptibility between individuals and populations. In this chapter, after an outline of research approaches, specific susceptibility and resistance genes are reviewed before data relevant to particular infectious diseases are summarized.


Many different types of studies have been undertaken to search for genetic effects on susceptibility to infectious diseases. Most of these have focused on particular candidate genes, and more recently some genome-wide studies have been undertaken, However, different approaches are required to estimate the magnitude of the genetic component to variable susceptibility.

Family Clustering

For some infections, such as leprosy, family clustering is well recognized,2 but with infectious ...

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