Genetic susceptiblilty to infectious diseases
Genetic variation in response to infection provides a powerful tool for analysis of infectious disease.
In our laboratory we have used both population-based and family-based genetic allelic association and
linkage analyses to study the role of candidate genes in disease susceptibility, and in determining
response to vaccination. This has demonstrated roles for SLC11A1 (formerly NRAMP1), the IL4-IL9 gene
cluster, the type I receptor (IFNGR1) for inteferon-gamma (IFN-γ), a cluster of chemokine genes on chromosome
17q11.2, and genes within the class II and class III regions of the MHC in determining susceptibility to
leprosy, tuberculosis and leishmaniasis, and in regulating immune response to mycobacterial and
We are using a combination of allelic association mapping and sequence analysis
to pinpoint the disease- or immune response-associated functional variants in these candidate genes.
Microsatellite genome scans have been used to identify new regions of the genome carrying putative disease
susceptibility genes for tuberculosis, leprosy and visceral leishmaniasis. We are currently working in
India, The Sudan, and Brazil to improve our sample sizes of affected individuals plus parents for all
three diseases to facilitate fine mapping of these genes using family-based transmission disequilibrium
tests of allelic association.