Chapter 26 : Immunogenetics of the Host Response to Bacteria and Parasites in Humans

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The role of genetic factors in common infectious diseases can be investigated by the analysis of several complementary traits. These traits include clinical phenotypes, which are generally binary (i.e., affected or unaffected); biological phenotypes, such as measures of infection, which may be quantitative (e.g., fecal egg counts in schistosomiasis) or binary (seropositive/seronegative); and measures of the immune response. Sections in this chapter focus on the main findings obtained in studies of susceptibility or resistance to mycobacterial and certain parasitic infections. Tuberculosis and leprosy, the most common human mycobacterial diseases, are caused by and , respectively. Many studies of familial aggregation, twin studies, and segregation analyses have clearly shown that leprosy susceptibility has a significant genetic component. Association studies between leprosy and HLA have provided other lines of evidence for the role of genetic factors in diseases caused by . In tuberculoid leprosy, the most consistent results were obtained for HLA-DR2. Segregation analyses on malaria infection levels have been performed in populations from Cameroon and Burkina Faso. Infection levels were assessed by multiple measurements of parasitemia, and the data were adjusted for factors known to influence parasitemia, such as season, area of residence, and age of the subject.

Citation: Abel L, Casanova J. 2002. Immunogenetics of the Host Response to Bacteria and Parasites in Humans, p 395-406. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch26

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Summary of the methods and strategies used to identify the genes and genetic polymorphisms involved in human infectious diseases. The genetic etiology of rare Mendelian disorders can be determined by several strategies. Linkage analysis is usually the first step in the positional cloning approach, although the identification of visible cytogenetic rearrangements can be of great help in the mapping of the gene. Another strategy, known as the candidate gene approach (“by hypothesis”), involves the prior selection of genes (from animal models or in vitro experiments), which are then tested by functional arrays and/or mutation detection. Another promising strategy, which may be more fruitful in the future, is based on analysis of the differential expressions of genes in tissues from affected and healthy individuals. In common infectious diseases, linkage studies (model based or model free) are used to search for a chromosomal region that segregates nonrandomly with the infectious disease-related phenotype within families. The role of polymorphisms of candidate genes located within this candidate region is tested by population-based or family-based association studies. Candidate genes by hypothesis can also be chosen on the basis of their function or homology to animal loci. Evidence for an association should be validated by functional studies to determine whether the detected polymorphism modifies gene expression or the gene product in a manner that may affect susceptibility to the disease.

Citation: Abel L, Casanova J. 2002. Immunogenetics of the Host Response to Bacteria and Parasites in Humans, p 395-406. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch26
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